Osama M Ahmed | Beni-Suef University (original) (raw)

Papers by Osama M Ahmed

Research paper thumbnail of Navel orange peel hydroethanolic extract, naringin and naringenin have anti-diabetic potentials in type 2 diabetic rats

The therapy of Type 2 Diabetes Mellitus (T2DM) stays a challenging issue. During the last decade,... more The therapy of Type 2 Diabetes Mellitus (T2DM) stays a challenging issue. During the last decade, there has been an interest in the expansion of anti-diabetic drugs especially those of natural sources. Thus, the aim of this study was to assess the anti-hyperglycemic and the anti-hyperlipidemic effects as well as the anti-oxidant activities of navel orange hydroethanolic extract and its constituting flavonoids naringin and naringenin on nicotineamide (NA)/streptozotocin (STZ)-induced type 2 diabetic rats. To induce T2DM, 16 h-fasted rats were intraperitoneally injected with STZ at dose of 50 mg/kg body weight (b. w.), 15 min after the intraperitoneal administration of NA (120 mg/kg b. w.). The NA/STZ-induced type 2 diabetic rats were orally treated with navel orange peel hydroethanolic extract, naringin and narengenin at dose level of 100 mg/kg b. w./day for 4 weeks. The treatments with navel orange peel hydroethanolic extract, naringin and narengenin potentially alleviated the lowered serum insulin and C-peptide levels, the depleted liver glycogen content, the elevated liver glucose-6-phosphatase and glycogen phosphorylase activities, the deteriorated serum lipid profile, and the suppressed liver antioxidant defense system of NA/STZ-induced type 2 diabetic rats. The treatments also enhanced the mRNA expression of insulin receptor b-subunit, GLUT4 and adiponectin in adipose tissue of STZ/NA-induced type 2 diabetic rats. In conclusion, the navel orange peel hydroethanolic extract, naringin and naringenin have potent anti-diabetic effects in NA/STZ-induced type 2 diabetic rats via their insulinotropic effects and insulin improving action which in turn may be mediated through enhancing insulin receptor, GLUT4 and adiponectin expression in adipose tissue.

Research paper thumbnail of Quercetin and low level laser therapy promote wound healing process in diabetic rats via structural reorganization and modulatory effects on inflammation and oxidative stress

A B S T R A C T This study aimed to evaluate the effect of quercetin and the photo-stimulatory ef... more A B S T R A C T This study aimed to evaluate the effect of quercetin and the photo-stimulatory effect of low energy 632.8 nm laser irradiation on excisional wound healing in non-diabetic and diabetic rats. Streptozotocin (45 mg/kg body weight) was intraperitoneally applied for diabetes induction. A full-thickness skin wound (2 × 2 cm 2) was aseptically created with a scalpel in non-diabetic and diabetic rats on the shaved back of the animals. The wounded non-diabetic and diabetic rats were treated every other day with quercetin by oral gavage at dose 25 mg/kg body weight and/or with low level laser therapy (LLLT) for 14 days. The wound closure percent calculated during the course of the experiment at days 1, 7 and 14 was remarkably increased as a result of treatment of non-diabetic and diabetic wounded rats with quercetin and LLLT; the treatment with both was the most potent. The elevated blood glucose and the lowered serum insulin levels were significantly improved in diabetic wounded rats treated with quercetin and LLLT as compared to the diabetic wounded control. The histological findings indicated that the wounded skin showed a marked increase in collagen fibers which become well oriented in sub-epidermal tissue, intact epidermis and presence of hyperplasia covering well-developed granulation tissue in the wounded rats treated with quercetin and LLLT as compared to the corresponding wounded control. The elevated levels of serum pro-inflammatory cytokines, IL-1β and TNF-α, as well as PGE-2 and LTB-4 were decreased in non-diabetic and diabetic wounded rats with quercetin and LLLT while the lowered level of serum anti-inflammatory cytokine, IL-10, was increased. The augmented oxidative stress represented by increased serum lipid peroxides level was decreased and the serum level of non-enzymatic anti-oxidant glu-tathione was increased as a result of treatment with quercetin and LLLT. Thus, it can be suggested that the improvements in glycemic state, cytokines involved in inflammation and antioxidant defense system as well as structural reorganization after treatment with quercetin and LLLT may play pivotal roles in promoting the wound healing process. The study also concluded that the treatment with quercetin in association with LLLT was better in improving wound healing in non-diabetic and diabetic rats than the use of either of each.

Research paper thumbnail of SUBLETHAL EFFECTS OF FOOD FLAVOUR FURFURAL ON HAEMATOLOGICAL INDICES AND VARIOUS SERUM BIOMARKERS IN MALE ALBINO RATS

This study aims to assess the effect of furfural, an aldehyde commonly used as food flavor in man... more This study aims to assess the effect of furfural, an aldehyde commonly used as food flavor in many foods, on the hematological and biochemical aspects in male albino rat. The experimental animals used in this study were divided into four groups. The control group was given a daily volume of the vehicle dimethyl sulfoxide (DMSO) whereas the other three groups were orally administered furfural for 8 weeks in sublethal doses of 3.18, 6.36 and 12.72 mg/kg b.w. respectively. The Obtained results revealed a decrease in red blood cells (RBCs) count, packed cell volume (PCV) and hemoglobin content and an increase in mean cell volume (MCV) and mean cell haemoglobin content (MCH) in rats received furfural in a dose dependent manner. The white blood cells (WBC) count was decreased especially eosinophil percentage which was depleted in the low and medium doses groups. Furfural elevated serum liver enzymes activities and total bilirubin concentration. The serum total protein and albumin levels were increased in medium and high doses groups, while globulin level, was elevated only in low dose group. Furfural elevated serum urea level but did not affect serum AFP and CA 19.9 levels in all groups. In conclusion, furfural administration to rats is highly able to induce a sort of macrocytic anemia, leucopenia, esinopenia as well as marked disturbances in liver and renal functions, but there is no evidence of carcinogenic effect detected by tumor markers.

Research paper thumbnail of EXPERIMENTAL STUDY Bee Venom and Hesperidin Effectively Mitigate Complete Freund's Adjuvant-Induced Arthritis Via Immunomodulation and Enhancement of Antioxidant Defense System

Objectives: This study aims to assess the antirheumatic activity of bee venom (BV) and/or hesperi... more Objectives: This study aims to assess the antirheumatic activity of bee venom (BV) and/or hesperidin as natural products in complete Freund's adjuvant (CFA)-induced arthritis in male Wistar rats. Material and methods: Rheumatoid arthritis was induced in 30 male Wistar rats (weight 130 g to 150 g; age 10 to 12 weeks) by subcutaneous injection of CFA into the right hind paw of the rats. The rats were divided into five groups of six rats in each and administered the following regimens for 21 days: Normal group (given the equivalent volume of saline and carboxymethylcellulose), arthritic group (given the equivalent volume of saline and carboxymethylcellulose), arthritic group treated with BV (treated with BV along with carboxymethylcellulose), arthritic group treated with hesperidin (treated with hesperidin along with saline), and arthritic group treated with BV and hesperidin (treated with BV and hesperidin concurrently). Results: Bee venom and/or hesperidin successfully reversed the CFA-arthritis-induced increases in right hind leg paw swelling, leukocytes' count, liver lipid peroxidation, serum inflammatory cytokine interleukin (IL-2 and IL-12) levels and spleen tumor necrosis factor-alpha messenger ribonucleic acid expression. Moreover, the CFA-induced down-regulation in serum IL-10 level and spleen IL-4 messenger ribonucleic acid expression as well as the deterioration in the antioxidant defense system were significantly improved as a result of BV and hesperidin administration. Both treatments also markedly counteracted the severe inflammatory changes and leukocytic infiltration in the periarticular tissue of the ankle joints. In addition, BV and hesperidin obviously amended the lymphoid hyperplasia in white pulps of spleen as well as the widening of the medulla and mononuclear cell infiltration found in thymus. Conclusion: Bee venom and hesperidin administration produced their ameliorative effects on rheumatoid arthritis via their antioxidant, antiinflammatory and immunomodulatory potentials. BV plus hesperidin particularly seemed to be the most potent in improving rheumatoid arthritis in Wistar rats.

Research paper thumbnail of Antihyperglycemic Effect of Crude Extracts of Some Egyptian Plants and Algae

Diabetes mellitus is a major global health problem. Various plant extracts have proven antidiabet... more Diabetes mellitus is a major global health problem. Various plant extracts have proven antidiabetic activity and are considered as promising substitution for antidiabetic drugs. The antihyperglycemic effect of 16 plants and 4 algae, commonly used in Egypt for the treatment of diabetes mellitus, was investigated. A diabetes model was induced by intra-peritoneal injection of nicotinamide (120 mg/kg body weight [b.wt.]), then streptozotocin (200 mg/kg b.wt.) after 15 min. Hydroethanolic extracts (80%) of the plants and algae under investigation were prepared. The extracts were orally administered to nicotinamide-streptozotocin–induced diabetic mice by a gastric tube at doses 10 or 50 mg/kg b.wt. for 1 week. The antidiabetic activity was assessed by detection of serum glucose concentrations at the fasting state and after 2 h of oral glucose loading (4.2 mg/kg b.wt.). Extracts prepared from Cassia acutifolia, Fraxinus ornus, Salix aegyptiaca, Cichorium intybus, and Eucalyptus globulus showed the highest antihyperglycemic activity among the tested plants. Extracts prepared from Sonchus oleraceus, Bougainvillea spectabilis (leaves), Plantago psyllium (seeds), Morus nigra (leaves), and Serena repens (fruits) were found to have antihyperglycemic potentials. Extracts prepared from Caulerpa lentillifera and Spirulina versicolor showed the most potent antihyperglycemic activity among the tested algae. However, some of the tested plants have in-sulinotropic effects, all assessed algae have not. Identification of lead compounds from these plants and algae for novel antidiabetic drug development is recommended. KEY WORDS: antihyperglycemic alga antihyperglycemic plant diabetes mellitus streptozotocin type 2

Research paper thumbnail of Stem Cell Therapies in Regenerative Medicine and Diabetes Mellitus: Advances, Constraints and Future Prospects

Stem cell therapy is one of the most promising treatments for the near future. This kind of thera... more Stem cell therapy is one of the most promising treatments for the near future. This kind of therapy can ameliorate or even reverse some diseases and have potential applications in regenerative and replacement medicines and diabetes mellitus. The different types of stem cells such as embryonic stem cells, induced pluripotent stem cells and adult stem cells have been proved to be operational in treating diabetes mellitus with clear limitations. The prevalence of diabetes mellitus type 1 and type 2 continues to rise and its complications are serious and may lead to death. The current treatment methods, other than stem cell therapy, do not treat the main causes of the disease and have many limitations. Although insulin injection is the standard therapy for type 1 diabetes mellitus, its exogenous injection cannot mimic insulin secretion from normal β-cells when blood glucose changes all the time. Thus, how to generate new β-cells is an important approach for the treatment of type 1 diabetes mellitus. Isolated islets are fragile and susceptible to pro-apoptotic factors and poorly proliferative. In contrast, mesenchymal stem cells (MSCs) are highly proliferative, anti-apoptotic and pluripotent to differentiate toward various cell types. The electrofusion between islets’ cells and MSCs produced fusion islets’ cells that are more resistant to apoptosis and are able to maintain insulin secretion for long periods. The stem cell therapy is also used for treatment of type 2 diabetes mellitus as well because the disease later progresses to β-cell dysfunction. Stem cell therapies were clinically applied for improvement of insulin sensitivity and metabolic control in long standing type 2 diabetes mellitus. In addition to the applications of stem cells in the cell therapy of diabetes mellitus, recent trends of studies tend to use the direct reprogrammed adult somatic cells especially endoderm-derived adult cells transdifferentiated into insulin secretory pancreatic β-cells. However, the use of stem cells especially human embryonic stem cells in research and therapy is subjected to limitations and constraints in many countries due to ethical and religious concerns. In this article, the types of stem cells and their resources and to what extent stem cell research can lead to progresses in regenerative medicine and diabetes mellitus therapies are reviewed. It also sheds light on ethical concerns and future hopes of stem cell use in research and therapy.

Research paper thumbnail of Effects of Purslane Shoot and Seed Ethanolic Extracts on Doxorubicin-Induced Testicular Toxicity in Albino Rats

The clinical usefulness of anthracycline antineoplastic antibiotic, doxorubicin (DOX) is restrict... more The clinical usefulness of anthracycline antineoplastic antibiotic, doxorubicin (DOX) is restricted since it has several acute and chronic side effects. The effect of doxorubicin (4 mg/kg b.w/week) without or with oral administration of purslane (Portulaca oleracea) shoot ethanolic extract (50mg/kg b.w./day) and purslane seed ethanolic extract (50mg/kg b.w./day) co-treatments for 6 weeks was evaluated in adult male rats. Serum testosterone luteinizing hormone (LH), follicle stimulating hormone (FSH) level were assayed. Testis lipid peroxidation (indexed by MDA) and antioxidants like glutathione (GSH), glutathione-S-transferase (GST), peroxidase (POX), superoxide dismutase (SOD), catalase (CAT) levels in testis were assessed. The data revealed a significant decrease in serum levels concentration of testosterone, LH and FSH levels in doxorubicin-injected rats. In addition, testis glutathione, glutathione transferase, peroxidase, SOD and CAT levels were decreased while lipid peroxidation concentration in the testis was increased as a result of doxorubicin injection. Co-administration of ethanolic purslane and seed extracts potentially improved the adverse changes in serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) levels with an increase in testis antioxidants levels and reduction in lipid peroxidation. In conclusion, it can be suggested that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX testicular toxicity without harmful side effects. [Walaa G. Hozayen; Osama M. Ahmed and Haidy Tamer Abo Sree Effects of Ethanolic Purslane Shoot and Seed Extracts on Doxorubicin-Induced Testicular Toxicity in Albino Rats. Life Sci J 2013; 10(3): 2550-2558]. (ISSN: 1097-8135). http://www.lifesciencesite.com. 369

Research paper thumbnail of Effects of Purslane Shoot and Seed Ethanolic Extracts on Doxorubicin-Induced Hepatotoxicity in Albino Rats

Doxorubicin (DOX), an anthracycline antibiotic, is a broad-spectrum antineoplastic agent, which i... more Doxorubicin (DOX), an anthracycline antibiotic, is a broad-spectrum antineoplastic agent, which is commonly used in the treatment of uterine, ovarian, breast and lung cancers, Hodgkin's disease and soft tissue sarcomas as well as in several other cancer types. The effect of doxorubicin (4 mg/kg b.w./week) without or with oral administration of ethanolic purslane (Portulaca oleracea) shoot (leaves and stems) extract (50 mg/kg b.w./day) or ethanolic purslane seeds extract (50 mg/kg b.w./day) co-treatments for 6 weeks was evaluated in adult male rats. Serum ALT, AST, ALP, GGT, total bilirubin, total protein and albumin levels were assayed. Lipid peroxidation (indexed by MDA) and antioxidants like hepatic glutathine, glutathione transferase, peroxidase, superoxide dismutase and catalase were assessed. There was an increase in serum levels of ALT, AST, ALP, GGT and total bilirubin. In addition, hepatic glutathine, glutathione transferase, peroxidase, superoxide dismutase and catalase activities were decreased while lipid peroxidation in the liver was increased. Co-administration of ethanolic purslane shoot and seed extracts successfully improved the adverse changes in the liver functions with an increase in antioxidants activities and reduction of lipid peroxidation. In coclusion, it can be supposed that dietary purslane shoot and seed extracts' supplementation may provide a cushion for a prolonged therapeutic option against DOX hepatopathy without harmful side effects. However, further clinical studies are required to assess the safety and efficacy of these extract in human beings. [Osama M. Ahmed; Walaa G. Hozayen and Haidy Tamer Abo Sree. Effects of Ethanolic Purslane Shoot and Seed Extracts on Doxorubicin-Induced Hepatotoxicity in Albino Rats. Life Sci J 2013; 10(4): 67-74]. (ISSN: 1097-8135). http://www.lifesciencesite.com. 10

Research paper thumbnail of PREVENTIVE EFFECT OF SPIRULINA VERSICOLOR AND ENTEROMORPHA FLEXUOSA ETHANOLIC EXTRACTS AGAINST DIETHYLNITROSAMINE/BENZO(A)PYRENE-INDUCED HAPATOCARCINOGENCITY IN RATS

This study is conducted to assess the preventive effects of Spirulina versicolor and Enteromorpha... more This study is conducted to assess the preventive effects of Spirulina versicolor and Enteromorpha flexuosa ethanolic extracts on hepatocarcingenesis induced by diethylnitrosamine (DEN)/benzo(a)pyrene (BP) in albino rats. In vitro anti-proliferative effect of both extracts on hepatocarcinoma cell lines (HepG2) was also evaluated and was found to be moderate. After two weeks of single dose of DEN (200 mg/kg b. wt; intraperitoneal), BP, a promotor of carcinogenesis, was intraperitoneally injected (50 mg/kg b. wt) twice/week for 6 weeks. Spirulina versicolor and Enteromorpha flexuosa ethanolic extracts orally administered, at dose of 25 mg/kg b. wt/day, for 2 and 8 weeks starting from the day of DEN injection successfully counteract the carcinogenic effects of DEN and BP as evidenced by absence of precancerous oval hepatocytes and vesicular nuclei as well as decrease of tumor marker, alpha fetoprotein and proinflammatory cytokine, TNF-α levels in serum. In addition, the treatments improved DEN/BP-induced elevation of AST, ALT, LDH and γ-GGT activities, serum total bilirubin level and liver lipid peroxidation. They increased the lowered serum albumin level and antioxidant enzymes as well. In conclusion, Spirulina versicolor and Enteromorpha flexuosa ethanolic extracts successfully prevented the hepatocarcinogenic and hepatoxic effects of DEN and BP via enhancement of anti-oxidant defense system and suppression of oxidative stress and inflammation.

Research paper thumbnail of Antiurolithic and Antioxidant Influence of Pleurotus ostreatus and Agaricus bisporus Aqueous Extracts and Carvedilol in Male Rats

Urolithiasis, a urinary tract stone formation, is the major clinical result of hyperoxaluria. Hyp... more Urolithiasis, a urinary tract stone formation, is the major clinical result of hyperoxaluria. Hyperoxaluria was induced in Wistar rats by receiving 0.75% ethylene glycol (EG) (v/v) in drinking tap water for 9 weeks. Hyperoxaluric rats were treated with Pleurotus ostreatus (P. ostreatus) and Agaricus bisporus (A. bisporus) infusions (100 mg/kg b. w.) and carvedilol (30 mg/kg b. w.) daily during the last 7 weeks. The study revealed that P. ostreatus and A. bisporus aqueous extracts and carvedilol could successfully inhibit EG-induced reduction of body weight gain (BWG) and urine magnesium, increase of relative kidney weight (RKW) and elevation of serum, urine and kidney oxalate, urine calcium, urine sodium and urine phosphorus. In addition, serum concentrations of potassium and sodium were not significantly altered. The tested agents markedly reduced the decrease in levels of kidney alkaline phosphatase (ALP), kidney alanine aminotransferase (ALT), kidney aspartate aminotransferase (AST), kidney glutathione (GSH) and activities of kidney glutathione-S-transferase (GST), kidney superoxide dismutase (SOD), kidney glutathione peroxidase (GPX) and kidney catalase. It also caused decreases in the elevated kidney and serum nitric oxide (NO) and kidney lipid peroxidation (LPO). According to these results, it can be concluded that aqueous extracts of P. ostreatus and A. bisporus as well as carvedilol might have a preventive effect against urolithiasis induced by EG, and that effect might be performed through stimulation of the antioxidant defense system.

Research paper thumbnail of Curcumin Ameliorative Efficacy on Type 1 Diabetes Mellitus Coexisted with Rheumatoid Arthritis in Wistar Rats

This study was designed to evaluate the effect of curcumin on type 1 diabetes mellitus and/or rhe... more This study was designed to evaluate the effect of curcumin on type 1 diabetes mellitus and/or rheumatoid arthritis in male Wistar rats. Type 1 diabetes mellitus was induced by multiple-low dose intraperitoneal injection of streptozotocin at dose of 20 mg/kg b.wt/day for 5 consecutive days. Rheumatoid arthritis was induced in normal and diabetic rats by a single subcutaneous injection of 0.1 ml Freund's complete adjuvant into a footpad of the right hind leg of male rats. Diabetic, arthritic and diabetic/arthritic rats were orally treated with curcumin at dose level of 50 mg /kg b.wt /day for 21 days. The treatment of diabetic and diabetic/arthritic rats with curcumin significantly improved the impaired glucose tolerance, the lowered insulin level, the β-cell function and the deteriorated serum lipid profile. The disrupted pancreatic islets architecture and integrity were amended by curcumin administration. The increased ankle joint circumference, deleteriously affected ankle joint histological architecture, articular inflammatory cell infiltration, pannus formation, cartilage erosion and synovial hyperplasia in arthritic and diabetic/arthritic rats were counteracted by curcumin treatment. The elevated pro-inflammatory cytokines (TNF-α and IL-1β) levels and the lowered anti-inflammatory cytokine (IL-10) level in diabetic, arthritic and diabetic/arthritic rats, reflecting the dominance of T helper 1 over T helper 2, were significantly improved as a result of curcumin administration. In conclusion, curcumin could have both antidiabetic and antiarthritic potentials which may be mediated via its anti-inflammatoy and immunomodulatory potentials.

Research paper thumbnail of The chemopreventive effects of onion and garlic oils against valproic acid

Valproic acid the treatment of various seizure disorders, in the management of bipolar disorder a... more Valproic acid the treatment of various seizure disorders, in the management of bipolar disorder and migraine. In this study we wish to use natural oils, depending on their antioxidant effect, to reduce We stud The animals were divided into five groups: the 1 2 nd treated with onion, garlic or their mixture respectively. significant increase in liver and kidney oxidation shift in VPA treated rats and all were ameliorated after treatments especially

Research paper thumbnail of Impacts of the coexistence of diabetes and hypothyroidism on body weight gain, leptin and various metabolic aspects in albino rats

The present study was conducted to assess the interrelationship and the influence of the coexiste... more The present study was conducted to assess the interrelationship and the influence of the coexistence of diabetes and hypothyroidism on thyroid hormone levels, insulin levels and biochemical variables related to carbohydrate, lipid and protein metabolism in addition to thyroid gland and Islets of Langerhans histological changes and antioxidant defense system. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin to fasting albino rats at dose level of 45 mg/kg b. w. Hypothyroidism in diabetic and normal rats was induced by adding methimazole in drinking water (0.02% w/v) for 4 weeks. The obtained results revealed that hypothyroidism interacts with diabetes in a way that prevents the progress of the hyperglycemic state. This may be due to the increase in the insulin secretory response in diabetic hypothyroid than diabetic rats. Serum T3 level decreased in order in diabetic (− 26.63%), hypothyroid (− 61.89%) and diabetic hypothyroid (− 65.69%) rats while T4 level was increased in diabetic rats and decreased in hypothyroid ones. The decrease in T3 level in diabetic animals in spite of T4 increase may be attributed to the decrease in conversion of T4 to T3 as a result of hepatic 5′-DI decreased activity. Liver glycogen content was threefold decreased in diabetic rats and was not significantly altered in both hypothyroid and diabetic hypothyroid rats. The serum leptin level and body weight gain were decreased in diabetic and diabetic hypothyroid rats; the leptin level was more deteriorated in diabetic hypothyroid rats while body weight gain was more affected in diabetic rats. Serum triglycerides level was more increased in diabetic rats than in diabetic hypothyroid ones on one hand, while total lipids, total cholesterol, LDL-cholesterol levels as well as cardiovascular indices were more deteriorated in diabetic hypothyroid rats than diabetic ones on the other hand. Serum total protein and globulin levels were decreased in diabetic rats and were increased in hypothyroid and diabetic hypothyroid rats. Hepatic total thiols and glutathione contents and catalase and peroxidase activity were profoundly decreased in diabetic rats while they (except glutathione) were increased in hypothyroid and diabetic hypothyroid rats. In conclusion, the hypothyroidism may have a counteracting effect on the hyperglycemic state and the elevated serum T4 level as well as the deteriorated antioxidant defense system found in diabetes mellitus, but both experimentally-induced diseases may synergize in inducing more elevation of serum total lipids, total cholesterol and LDL-cholesterol and more decrease in leptin levels.

Research paper thumbnail of Stem Cell Therapies in Regenerative Medicine and Diabetes Mellitus: Advances, Constraints and Future Prospects

Citation: Ahmed OM, Sayed HM. Stem Cell Therapies in Regenerative Medicine and Diabetes Mellitus:... more Citation: Ahmed OM, Sayed HM. Stem Cell Therapies in Regenerative Medicine and Diabetes Mellitus: Advances, Constraints and Future Prospects. J Transplant Stem Cel Biol. 2016;3(1): 22.

Research paper thumbnail of Stem Cell Therapies in Regenerative Medicine and Diabetes Mellitus: Advances, Constraints and Future Prospects

Stem cell therapy is one of the most promising treatments for the near future. This kind of thera... more Stem cell therapy is one of the most promising treatments for the near future. This kind of therapy can ameliorate or even reverse some diseases and have potential applications in regenerative and replacement medicines and diabetes mellitus. The different types of stem cells such as embryonic stem cells, induced pluripotent stem cells and adult stem cells have been proved to be operational in treating diabetes mellitus with clear limitations. The prevalence of diabetes mellitus type 1 and type 2 continues to rise and its complications are serious and may lead to death. The current treatment methods, other than stem cell therapy, do not treat the main causes of the disease and have many limitations. Although insulin injection is the standard therapy for type 1 diabetes mellitus, its exogenous injection cannot mimic insulin secretion from normal β-cells when blood glucose changes all the time. Thus, how to generate new β-cells is an important approach for the treatment of type 1 diabetes mellitus. Isolated islets are fragile and susceptible to pro-apoptotic factors and poorly proliferative. In contrast, mesenchymal stem cells (MSCs) are highly proliferative, anti-apoptotic and pluripotent to differentiate toward various cell types. The electrofusion between islets’ cells and MSCs produced fusion islets’ cells that are more resistant to apoptosis and are able to maintain insulin secretion for long periods. The stem cell therapy is also used for treatment of type 2 diabetes mellitus as well because the disease later progresses to β-cell dysfunction. Stem cell therapies were clinically applied for improvement of insulin sensitivity and metabolic control in long standing type 2 diabetes mellitus. In addition to the applications of stem cells in the cell therapy of diabetes mellitus, recent trends of studies tend to use the direct reprogrammed adult somatic cells especially endoderm-derived adult cells transdifferentiated into insulin secretory pancreatic β-cells. However, the use of stem cells especially human embryonic stem cells in research and therapy is subjected to limitations and constraints in many countries due to ethical and religious concerns. In this article, the types of stem cells and their resources and to what extent stem cell research can lead to progresses in regenerative medicine and diabetes mellitus therapies are reviewed. It also sheds light on ethical concerns and future hopes of stem cell use in research and therapy.

Research paper thumbnail of DADS Published article w volume and pages HepatomaRes1267-6673586_183215.pdf

Aim: This study was conducted to assess the in vivo and in vitro anti-tumor effects of diallyl di... more Aim: This study was conducted to assess the in vivo and in vitro anti-tumor effects of diallyl disulfi de (DADS) against Ehrlich ascites carcinoma (EAC) and to suggest its probable mechanism of action. Methods: EAC was induced in female mice by intraperitoneal injection of EAC-cells from stock mice. EAC-bearing mice were orally treated with 100 mg/kg body weight for 2 weeks beginning from the 1st day of EAC intraperitoneal transplantation. Cytotoxicity effects of DADS against EAC-cells in vitro were investigated at different concentrations (0, 6.25, 12.5, 25, 50, and 100 μg/mL) of DADS using trypan blue exclusion assay. Results: Data from this study exhibited a signifi cant decrease in EAC-aliquot volume as well as total and alive EAC-cell number and a marked increase in dead EAC-cell number and percent in EAC-bearing mice treated with DADS as compared with EAC-bearing control. These changes were consistent with increased number of cells which exhibited phenotypic apoptotic signs marked by a decrease in the expression of anti-apoptotic protein Bcl-2, an increase of pro-apoptotic and cell cycle arrest mediator p53 and an elevation of DNA fragmenting indicator terminal deoxynucleotidyl transferase in EAC-bearing mice treated with DADS. In addition, the tumor marker sialic acid level was markedly decreased in plasma and Ehrlich ascites in EAC-bearing mice treated with DADS. In vitro, DADS also produced anti-proliferative and anti-tumor cytotoxic potentials against EAC. Conclusion: DADS may have anti-cancer effects which may be mediated via modulation of apoptosis and cell cycle arrest.

Research paper thumbnail of BIOINFORMATICS ANALYSIS OF SOME FUNCTIONAL GENES AND PROTEINS INVOLVED IN OBESITY-INDUCED TYPE 2 DIABETES

The incidence of type-2 diabetes is rising rapidly worldwide, mainly because of the increase in t... more The incidence of type-2 diabetes is rising rapidly worldwide, mainly because of the increase in the incidence of obesity, which is an important risk factor for this condition. Both obesity and type-2 diabetes are complex genetic traits but they also share some nongenetic risk factors. Differences among individuals in their susceptibility to both these conditions probably reflect their genetic constitutions. The dramatic improvements in genomic and bioinformatic resources are accelerating the pace of gene discovery. It is tempting to speculate the key susceptible genes/proteins that bridges diabetes mellitus and obesity. In this regard, we evaluated the role of several genes/proteins that are believed to be involved in the evolution of obesity associated diabetes through thorough literature search. Also we analyzed the data pertaining to genes of these proteins extracted from the databases that are available online for free access. The functional cDNA sequences of these genes/proteins are extracted from National Center for Biotechnology Information (NCBI) and Ensembl Genome Browser. Our bioinformatic analysis reports 21 genes as ominous link with obesity associated diabetes. Also this study indicated that, adipose tissue is now known to express and secrete a variety of metabolites, hormones and cytokines that have been implicated in the development of insulin resistance.This bioinformatic study will be useful for future studies towards therapeutic inventions of obesity associated type-2 diabetes.

Research paper thumbnail of Ulva lactuca polysaccharides prevent wistar rat breast carci 022717

Background: Recently, several research studies have been focused on the isolation and function of... more Background: Recently, several research studies have been focused on the isolation and function of the polysaccharides derived from different algal species, which revealed multiple biological activities such as antioxidant and antitumor activities. This study assesses the possible breast cancer chemopreventive properties of common seaweeds, sea lettuce, Ulva lactuca (ulvan) polysaccharides using in vitro bioassays on human breast cancer cell line (MCF-7) and an in vivo animal model of breast carcinogenesis. Methods: Cytotoxic effect of ulvan polysaccharides on MCF-7 was tested in vitro. For an in vivo investigation, a single dose of 25 mg/kg body weight 7,12-dimethylbenz[a]anthracene (DMBA) and ulvan polysaccharides (50 mg/kg body weight every other day) for 10 weeks were administered orally to the Wistar rats. Results: Deleterious histopathological alterations in breast tissues including papillary cyst adenoma and hyperplasia of ductal epithelial lining with intraluminal necrotic materials and calcifications were observed in the DMBA-administered group. These lesions were prevented in the DMBA-administered group treated with ulvan polysaccharides. The immunohistochemical sections depicted that the treatment of DMBA-administered rats with ulvan polysaccharides markedly increased the lowered pro-apoptotic protein, p53, and decreased the elevated anti-apoptotic marker, bcl2, expression in the breast tissue. The elevated lipid peroxidation and the suppressed antioxidant enzyme activities in DMBA-administered control were significantly prevented by the treatment with ulvan polysaccharides. The elevated levels of inflammatory cytokines tumor necrosis factor-α and nitric oxide were significantly ameliorated in DMBA-administered rats treated with ulvan polysaccharides as compared to DMBA-administered control. Conclusion: In conclusion, ulvan polysaccharides at the level of initiation and promotion might have potential chemopreventive effects against breast carcinogenesis. These preventive effects may be mediated through the augmentation of apoptosis, suppression of oxidative stress and inflammation, and enhancement of antioxidant defense system.

Research paper thumbnail of Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity

Adipokines are bioactive molecules that regulate several physiological functions such as energy b... more Adipokines are bioactive molecules that regulate several physiological functions such as energy balance, insulin sensitization, appetite regulation, inflammatory response, and vascular homeostasis. They include proinflammatory cytokines such as adipocyte fatty acid binding protein (A-FABP) and anti-inflammatory cytokines such as adiponectin, as well as vasodilator and vasoconstrictor molecules. In obesity and type II diabetes mellitus (DM), insulin resistance causes impairment of the endocrine function of the perivascular adipose tissue, an imbalance in the secretion of vasoconstrictor and vasodilator molecules, and an increased production of reactive oxygen species. Recent studies have shown that targeting plasma levels of adipokines or the expression of their receptors can increase insulin sensitivity, improve vascular function, and reduce the risk of cardiovascular morbidity and mortality. Several reviews have discussed the potential of adipokines as therapeutic targets for type II DM and obesity; however, this review is the first to focus on their therapeutic potential for vascular dysfunction in type II DM and obesity.

Research paper thumbnail of Relationships between Oxidative Stress, Cancer Development and Therapeutic Interventions Cancer Development and Therapeutic Interventions

Research paper thumbnail of Navel orange peel hydroethanolic extract, naringin and naringenin have anti-diabetic potentials in type 2 diabetic rats

The therapy of Type 2 Diabetes Mellitus (T2DM) stays a challenging issue. During the last decade,... more The therapy of Type 2 Diabetes Mellitus (T2DM) stays a challenging issue. During the last decade, there has been an interest in the expansion of anti-diabetic drugs especially those of natural sources. Thus, the aim of this study was to assess the anti-hyperglycemic and the anti-hyperlipidemic effects as well as the anti-oxidant activities of navel orange hydroethanolic extract and its constituting flavonoids naringin and naringenin on nicotineamide (NA)/streptozotocin (STZ)-induced type 2 diabetic rats. To induce T2DM, 16 h-fasted rats were intraperitoneally injected with STZ at dose of 50 mg/kg body weight (b. w.), 15 min after the intraperitoneal administration of NA (120 mg/kg b. w.). The NA/STZ-induced type 2 diabetic rats were orally treated with navel orange peel hydroethanolic extract, naringin and narengenin at dose level of 100 mg/kg b. w./day for 4 weeks. The treatments with navel orange peel hydroethanolic extract, naringin and narengenin potentially alleviated the lowered serum insulin and C-peptide levels, the depleted liver glycogen content, the elevated liver glucose-6-phosphatase and glycogen phosphorylase activities, the deteriorated serum lipid profile, and the suppressed liver antioxidant defense system of NA/STZ-induced type 2 diabetic rats. The treatments also enhanced the mRNA expression of insulin receptor b-subunit, GLUT4 and adiponectin in adipose tissue of STZ/NA-induced type 2 diabetic rats. In conclusion, the navel orange peel hydroethanolic extract, naringin and naringenin have potent anti-diabetic effects in NA/STZ-induced type 2 diabetic rats via their insulinotropic effects and insulin improving action which in turn may be mediated through enhancing insulin receptor, GLUT4 and adiponectin expression in adipose tissue.

Research paper thumbnail of Quercetin and low level laser therapy promote wound healing process in diabetic rats via structural reorganization and modulatory effects on inflammation and oxidative stress

A B S T R A C T This study aimed to evaluate the effect of quercetin and the photo-stimulatory ef... more A B S T R A C T This study aimed to evaluate the effect of quercetin and the photo-stimulatory effect of low energy 632.8 nm laser irradiation on excisional wound healing in non-diabetic and diabetic rats. Streptozotocin (45 mg/kg body weight) was intraperitoneally applied for diabetes induction. A full-thickness skin wound (2 × 2 cm 2) was aseptically created with a scalpel in non-diabetic and diabetic rats on the shaved back of the animals. The wounded non-diabetic and diabetic rats were treated every other day with quercetin by oral gavage at dose 25 mg/kg body weight and/or with low level laser therapy (LLLT) for 14 days. The wound closure percent calculated during the course of the experiment at days 1, 7 and 14 was remarkably increased as a result of treatment of non-diabetic and diabetic wounded rats with quercetin and LLLT; the treatment with both was the most potent. The elevated blood glucose and the lowered serum insulin levels were significantly improved in diabetic wounded rats treated with quercetin and LLLT as compared to the diabetic wounded control. The histological findings indicated that the wounded skin showed a marked increase in collagen fibers which become well oriented in sub-epidermal tissue, intact epidermis and presence of hyperplasia covering well-developed granulation tissue in the wounded rats treated with quercetin and LLLT as compared to the corresponding wounded control. The elevated levels of serum pro-inflammatory cytokines, IL-1β and TNF-α, as well as PGE-2 and LTB-4 were decreased in non-diabetic and diabetic wounded rats with quercetin and LLLT while the lowered level of serum anti-inflammatory cytokine, IL-10, was increased. The augmented oxidative stress represented by increased serum lipid peroxides level was decreased and the serum level of non-enzymatic anti-oxidant glu-tathione was increased as a result of treatment with quercetin and LLLT. Thus, it can be suggested that the improvements in glycemic state, cytokines involved in inflammation and antioxidant defense system as well as structural reorganization after treatment with quercetin and LLLT may play pivotal roles in promoting the wound healing process. The study also concluded that the treatment with quercetin in association with LLLT was better in improving wound healing in non-diabetic and diabetic rats than the use of either of each.

Research paper thumbnail of SUBLETHAL EFFECTS OF FOOD FLAVOUR FURFURAL ON HAEMATOLOGICAL INDICES AND VARIOUS SERUM BIOMARKERS IN MALE ALBINO RATS

This study aims to assess the effect of furfural, an aldehyde commonly used as food flavor in man... more This study aims to assess the effect of furfural, an aldehyde commonly used as food flavor in many foods, on the hematological and biochemical aspects in male albino rat. The experimental animals used in this study were divided into four groups. The control group was given a daily volume of the vehicle dimethyl sulfoxide (DMSO) whereas the other three groups were orally administered furfural for 8 weeks in sublethal doses of 3.18, 6.36 and 12.72 mg/kg b.w. respectively. The Obtained results revealed a decrease in red blood cells (RBCs) count, packed cell volume (PCV) and hemoglobin content and an increase in mean cell volume (MCV) and mean cell haemoglobin content (MCH) in rats received furfural in a dose dependent manner. The white blood cells (WBC) count was decreased especially eosinophil percentage which was depleted in the low and medium doses groups. Furfural elevated serum liver enzymes activities and total bilirubin concentration. The serum total protein and albumin levels were increased in medium and high doses groups, while globulin level, was elevated only in low dose group. Furfural elevated serum urea level but did not affect serum AFP and CA 19.9 levels in all groups. In conclusion, furfural administration to rats is highly able to induce a sort of macrocytic anemia, leucopenia, esinopenia as well as marked disturbances in liver and renal functions, but there is no evidence of carcinogenic effect detected by tumor markers.

Research paper thumbnail of EXPERIMENTAL STUDY Bee Venom and Hesperidin Effectively Mitigate Complete Freund's Adjuvant-Induced Arthritis Via Immunomodulation and Enhancement of Antioxidant Defense System

Objectives: This study aims to assess the antirheumatic activity of bee venom (BV) and/or hesperi... more Objectives: This study aims to assess the antirheumatic activity of bee venom (BV) and/or hesperidin as natural products in complete Freund's adjuvant (CFA)-induced arthritis in male Wistar rats. Material and methods: Rheumatoid arthritis was induced in 30 male Wistar rats (weight 130 g to 150 g; age 10 to 12 weeks) by subcutaneous injection of CFA into the right hind paw of the rats. The rats were divided into five groups of six rats in each and administered the following regimens for 21 days: Normal group (given the equivalent volume of saline and carboxymethylcellulose), arthritic group (given the equivalent volume of saline and carboxymethylcellulose), arthritic group treated with BV (treated with BV along with carboxymethylcellulose), arthritic group treated with hesperidin (treated with hesperidin along with saline), and arthritic group treated with BV and hesperidin (treated with BV and hesperidin concurrently). Results: Bee venom and/or hesperidin successfully reversed the CFA-arthritis-induced increases in right hind leg paw swelling, leukocytes' count, liver lipid peroxidation, serum inflammatory cytokine interleukin (IL-2 and IL-12) levels and spleen tumor necrosis factor-alpha messenger ribonucleic acid expression. Moreover, the CFA-induced down-regulation in serum IL-10 level and spleen IL-4 messenger ribonucleic acid expression as well as the deterioration in the antioxidant defense system were significantly improved as a result of BV and hesperidin administration. Both treatments also markedly counteracted the severe inflammatory changes and leukocytic infiltration in the periarticular tissue of the ankle joints. In addition, BV and hesperidin obviously amended the lymphoid hyperplasia in white pulps of spleen as well as the widening of the medulla and mononuclear cell infiltration found in thymus. Conclusion: Bee venom and hesperidin administration produced their ameliorative effects on rheumatoid arthritis via their antioxidant, antiinflammatory and immunomodulatory potentials. BV plus hesperidin particularly seemed to be the most potent in improving rheumatoid arthritis in Wistar rats.

Research paper thumbnail of Antihyperglycemic Effect of Crude Extracts of Some Egyptian Plants and Algae

Diabetes mellitus is a major global health problem. Various plant extracts have proven antidiabet... more Diabetes mellitus is a major global health problem. Various plant extracts have proven antidiabetic activity and are considered as promising substitution for antidiabetic drugs. The antihyperglycemic effect of 16 plants and 4 algae, commonly used in Egypt for the treatment of diabetes mellitus, was investigated. A diabetes model was induced by intra-peritoneal injection of nicotinamide (120 mg/kg body weight [b.wt.]), then streptozotocin (200 mg/kg b.wt.) after 15 min. Hydroethanolic extracts (80%) of the plants and algae under investigation were prepared. The extracts were orally administered to nicotinamide-streptozotocin–induced diabetic mice by a gastric tube at doses 10 or 50 mg/kg b.wt. for 1 week. The antidiabetic activity was assessed by detection of serum glucose concentrations at the fasting state and after 2 h of oral glucose loading (4.2 mg/kg b.wt.). Extracts prepared from Cassia acutifolia, Fraxinus ornus, Salix aegyptiaca, Cichorium intybus, and Eucalyptus globulus showed the highest antihyperglycemic activity among the tested plants. Extracts prepared from Sonchus oleraceus, Bougainvillea spectabilis (leaves), Plantago psyllium (seeds), Morus nigra (leaves), and Serena repens (fruits) were found to have antihyperglycemic potentials. Extracts prepared from Caulerpa lentillifera and Spirulina versicolor showed the most potent antihyperglycemic activity among the tested algae. However, some of the tested plants have in-sulinotropic effects, all assessed algae have not. Identification of lead compounds from these plants and algae for novel antidiabetic drug development is recommended. KEY WORDS: antihyperglycemic alga antihyperglycemic plant diabetes mellitus streptozotocin type 2

Research paper thumbnail of Stem Cell Therapies in Regenerative Medicine and Diabetes Mellitus: Advances, Constraints and Future Prospects

Stem cell therapy is one of the most promising treatments for the near future. This kind of thera... more Stem cell therapy is one of the most promising treatments for the near future. This kind of therapy can ameliorate or even reverse some diseases and have potential applications in regenerative and replacement medicines and diabetes mellitus. The different types of stem cells such as embryonic stem cells, induced pluripotent stem cells and adult stem cells have been proved to be operational in treating diabetes mellitus with clear limitations. The prevalence of diabetes mellitus type 1 and type 2 continues to rise and its complications are serious and may lead to death. The current treatment methods, other than stem cell therapy, do not treat the main causes of the disease and have many limitations. Although insulin injection is the standard therapy for type 1 diabetes mellitus, its exogenous injection cannot mimic insulin secretion from normal β-cells when blood glucose changes all the time. Thus, how to generate new β-cells is an important approach for the treatment of type 1 diabetes mellitus. Isolated islets are fragile and susceptible to pro-apoptotic factors and poorly proliferative. In contrast, mesenchymal stem cells (MSCs) are highly proliferative, anti-apoptotic and pluripotent to differentiate toward various cell types. The electrofusion between islets’ cells and MSCs produced fusion islets’ cells that are more resistant to apoptosis and are able to maintain insulin secretion for long periods. The stem cell therapy is also used for treatment of type 2 diabetes mellitus as well because the disease later progresses to β-cell dysfunction. Stem cell therapies were clinically applied for improvement of insulin sensitivity and metabolic control in long standing type 2 diabetes mellitus. In addition to the applications of stem cells in the cell therapy of diabetes mellitus, recent trends of studies tend to use the direct reprogrammed adult somatic cells especially endoderm-derived adult cells transdifferentiated into insulin secretory pancreatic β-cells. However, the use of stem cells especially human embryonic stem cells in research and therapy is subjected to limitations and constraints in many countries due to ethical and religious concerns. In this article, the types of stem cells and their resources and to what extent stem cell research can lead to progresses in regenerative medicine and diabetes mellitus therapies are reviewed. It also sheds light on ethical concerns and future hopes of stem cell use in research and therapy.

Research paper thumbnail of Effects of Purslane Shoot and Seed Ethanolic Extracts on Doxorubicin-Induced Testicular Toxicity in Albino Rats

The clinical usefulness of anthracycline antineoplastic antibiotic, doxorubicin (DOX) is restrict... more The clinical usefulness of anthracycline antineoplastic antibiotic, doxorubicin (DOX) is restricted since it has several acute and chronic side effects. The effect of doxorubicin (4 mg/kg b.w/week) without or with oral administration of purslane (Portulaca oleracea) shoot ethanolic extract (50mg/kg b.w./day) and purslane seed ethanolic extract (50mg/kg b.w./day) co-treatments for 6 weeks was evaluated in adult male rats. Serum testosterone luteinizing hormone (LH), follicle stimulating hormone (FSH) level were assayed. Testis lipid peroxidation (indexed by MDA) and antioxidants like glutathione (GSH), glutathione-S-transferase (GST), peroxidase (POX), superoxide dismutase (SOD), catalase (CAT) levels in testis were assessed. The data revealed a significant decrease in serum levels concentration of testosterone, LH and FSH levels in doxorubicin-injected rats. In addition, testis glutathione, glutathione transferase, peroxidase, SOD and CAT levels were decreased while lipid peroxidation concentration in the testis was increased as a result of doxorubicin injection. Co-administration of ethanolic purslane and seed extracts potentially improved the adverse changes in serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) levels with an increase in testis antioxidants levels and reduction in lipid peroxidation. In conclusion, it can be suggested that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX testicular toxicity without harmful side effects. [Walaa G. Hozayen; Osama M. Ahmed and Haidy Tamer Abo Sree Effects of Ethanolic Purslane Shoot and Seed Extracts on Doxorubicin-Induced Testicular Toxicity in Albino Rats. Life Sci J 2013; 10(3): 2550-2558]. (ISSN: 1097-8135). http://www.lifesciencesite.com. 369

Research paper thumbnail of Effects of Purslane Shoot and Seed Ethanolic Extracts on Doxorubicin-Induced Hepatotoxicity in Albino Rats

Doxorubicin (DOX), an anthracycline antibiotic, is a broad-spectrum antineoplastic agent, which i... more Doxorubicin (DOX), an anthracycline antibiotic, is a broad-spectrum antineoplastic agent, which is commonly used in the treatment of uterine, ovarian, breast and lung cancers, Hodgkin's disease and soft tissue sarcomas as well as in several other cancer types. The effect of doxorubicin (4 mg/kg b.w./week) without or with oral administration of ethanolic purslane (Portulaca oleracea) shoot (leaves and stems) extract (50 mg/kg b.w./day) or ethanolic purslane seeds extract (50 mg/kg b.w./day) co-treatments for 6 weeks was evaluated in adult male rats. Serum ALT, AST, ALP, GGT, total bilirubin, total protein and albumin levels were assayed. Lipid peroxidation (indexed by MDA) and antioxidants like hepatic glutathine, glutathione transferase, peroxidase, superoxide dismutase and catalase were assessed. There was an increase in serum levels of ALT, AST, ALP, GGT and total bilirubin. In addition, hepatic glutathine, glutathione transferase, peroxidase, superoxide dismutase and catalase activities were decreased while lipid peroxidation in the liver was increased. Co-administration of ethanolic purslane shoot and seed extracts successfully improved the adverse changes in the liver functions with an increase in antioxidants activities and reduction of lipid peroxidation. In coclusion, it can be supposed that dietary purslane shoot and seed extracts' supplementation may provide a cushion for a prolonged therapeutic option against DOX hepatopathy without harmful side effects. However, further clinical studies are required to assess the safety and efficacy of these extract in human beings. [Osama M. Ahmed; Walaa G. Hozayen and Haidy Tamer Abo Sree. Effects of Ethanolic Purslane Shoot and Seed Extracts on Doxorubicin-Induced Hepatotoxicity in Albino Rats. Life Sci J 2013; 10(4): 67-74]. (ISSN: 1097-8135). http://www.lifesciencesite.com. 10

Research paper thumbnail of PREVENTIVE EFFECT OF SPIRULINA VERSICOLOR AND ENTEROMORPHA FLEXUOSA ETHANOLIC EXTRACTS AGAINST DIETHYLNITROSAMINE/BENZO(A)PYRENE-INDUCED HAPATOCARCINOGENCITY IN RATS

This study is conducted to assess the preventive effects of Spirulina versicolor and Enteromorpha... more This study is conducted to assess the preventive effects of Spirulina versicolor and Enteromorpha flexuosa ethanolic extracts on hepatocarcingenesis induced by diethylnitrosamine (DEN)/benzo(a)pyrene (BP) in albino rats. In vitro anti-proliferative effect of both extracts on hepatocarcinoma cell lines (HepG2) was also evaluated and was found to be moderate. After two weeks of single dose of DEN (200 mg/kg b. wt; intraperitoneal), BP, a promotor of carcinogenesis, was intraperitoneally injected (50 mg/kg b. wt) twice/week for 6 weeks. Spirulina versicolor and Enteromorpha flexuosa ethanolic extracts orally administered, at dose of 25 mg/kg b. wt/day, for 2 and 8 weeks starting from the day of DEN injection successfully counteract the carcinogenic effects of DEN and BP as evidenced by absence of precancerous oval hepatocytes and vesicular nuclei as well as decrease of tumor marker, alpha fetoprotein and proinflammatory cytokine, TNF-α levels in serum. In addition, the treatments improved DEN/BP-induced elevation of AST, ALT, LDH and γ-GGT activities, serum total bilirubin level and liver lipid peroxidation. They increased the lowered serum albumin level and antioxidant enzymes as well. In conclusion, Spirulina versicolor and Enteromorpha flexuosa ethanolic extracts successfully prevented the hepatocarcinogenic and hepatoxic effects of DEN and BP via enhancement of anti-oxidant defense system and suppression of oxidative stress and inflammation.

Research paper thumbnail of Antiurolithic and Antioxidant Influence of Pleurotus ostreatus and Agaricus bisporus Aqueous Extracts and Carvedilol in Male Rats

Urolithiasis, a urinary tract stone formation, is the major clinical result of hyperoxaluria. Hyp... more Urolithiasis, a urinary tract stone formation, is the major clinical result of hyperoxaluria. Hyperoxaluria was induced in Wistar rats by receiving 0.75% ethylene glycol (EG) (v/v) in drinking tap water for 9 weeks. Hyperoxaluric rats were treated with Pleurotus ostreatus (P. ostreatus) and Agaricus bisporus (A. bisporus) infusions (100 mg/kg b. w.) and carvedilol (30 mg/kg b. w.) daily during the last 7 weeks. The study revealed that P. ostreatus and A. bisporus aqueous extracts and carvedilol could successfully inhibit EG-induced reduction of body weight gain (BWG) and urine magnesium, increase of relative kidney weight (RKW) and elevation of serum, urine and kidney oxalate, urine calcium, urine sodium and urine phosphorus. In addition, serum concentrations of potassium and sodium were not significantly altered. The tested agents markedly reduced the decrease in levels of kidney alkaline phosphatase (ALP), kidney alanine aminotransferase (ALT), kidney aspartate aminotransferase (AST), kidney glutathione (GSH) and activities of kidney glutathione-S-transferase (GST), kidney superoxide dismutase (SOD), kidney glutathione peroxidase (GPX) and kidney catalase. It also caused decreases in the elevated kidney and serum nitric oxide (NO) and kidney lipid peroxidation (LPO). According to these results, it can be concluded that aqueous extracts of P. ostreatus and A. bisporus as well as carvedilol might have a preventive effect against urolithiasis induced by EG, and that effect might be performed through stimulation of the antioxidant defense system.

Research paper thumbnail of Curcumin Ameliorative Efficacy on Type 1 Diabetes Mellitus Coexisted with Rheumatoid Arthritis in Wistar Rats

This study was designed to evaluate the effect of curcumin on type 1 diabetes mellitus and/or rhe... more This study was designed to evaluate the effect of curcumin on type 1 diabetes mellitus and/or rheumatoid arthritis in male Wistar rats. Type 1 diabetes mellitus was induced by multiple-low dose intraperitoneal injection of streptozotocin at dose of 20 mg/kg b.wt/day for 5 consecutive days. Rheumatoid arthritis was induced in normal and diabetic rats by a single subcutaneous injection of 0.1 ml Freund's complete adjuvant into a footpad of the right hind leg of male rats. Diabetic, arthritic and diabetic/arthritic rats were orally treated with curcumin at dose level of 50 mg /kg b.wt /day for 21 days. The treatment of diabetic and diabetic/arthritic rats with curcumin significantly improved the impaired glucose tolerance, the lowered insulin level, the β-cell function and the deteriorated serum lipid profile. The disrupted pancreatic islets architecture and integrity were amended by curcumin administration. The increased ankle joint circumference, deleteriously affected ankle joint histological architecture, articular inflammatory cell infiltration, pannus formation, cartilage erosion and synovial hyperplasia in arthritic and diabetic/arthritic rats were counteracted by curcumin treatment. The elevated pro-inflammatory cytokines (TNF-α and IL-1β) levels and the lowered anti-inflammatory cytokine (IL-10) level in diabetic, arthritic and diabetic/arthritic rats, reflecting the dominance of T helper 1 over T helper 2, were significantly improved as a result of curcumin administration. In conclusion, curcumin could have both antidiabetic and antiarthritic potentials which may be mediated via its anti-inflammatoy and immunomodulatory potentials.

Research paper thumbnail of The chemopreventive effects of onion and garlic oils against valproic acid

Valproic acid the treatment of various seizure disorders, in the management of bipolar disorder a... more Valproic acid the treatment of various seizure disorders, in the management of bipolar disorder and migraine. In this study we wish to use natural oils, depending on their antioxidant effect, to reduce We stud The animals were divided into five groups: the 1 2 nd treated with onion, garlic or their mixture respectively. significant increase in liver and kidney oxidation shift in VPA treated rats and all were ameliorated after treatments especially

Research paper thumbnail of Impacts of the coexistence of diabetes and hypothyroidism on body weight gain, leptin and various metabolic aspects in albino rats

The present study was conducted to assess the interrelationship and the influence of the coexiste... more The present study was conducted to assess the interrelationship and the influence of the coexistence of diabetes and hypothyroidism on thyroid hormone levels, insulin levels and biochemical variables related to carbohydrate, lipid and protein metabolism in addition to thyroid gland and Islets of Langerhans histological changes and antioxidant defense system. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin to fasting albino rats at dose level of 45 mg/kg b. w. Hypothyroidism in diabetic and normal rats was induced by adding methimazole in drinking water (0.02% w/v) for 4 weeks. The obtained results revealed that hypothyroidism interacts with diabetes in a way that prevents the progress of the hyperglycemic state. This may be due to the increase in the insulin secretory response in diabetic hypothyroid than diabetic rats. Serum T3 level decreased in order in diabetic (− 26.63%), hypothyroid (− 61.89%) and diabetic hypothyroid (− 65.69%) rats while T4 level was increased in diabetic rats and decreased in hypothyroid ones. The decrease in T3 level in diabetic animals in spite of T4 increase may be attributed to the decrease in conversion of T4 to T3 as a result of hepatic 5′-DI decreased activity. Liver glycogen content was threefold decreased in diabetic rats and was not significantly altered in both hypothyroid and diabetic hypothyroid rats. The serum leptin level and body weight gain were decreased in diabetic and diabetic hypothyroid rats; the leptin level was more deteriorated in diabetic hypothyroid rats while body weight gain was more affected in diabetic rats. Serum triglycerides level was more increased in diabetic rats than in diabetic hypothyroid ones on one hand, while total lipids, total cholesterol, LDL-cholesterol levels as well as cardiovascular indices were more deteriorated in diabetic hypothyroid rats than diabetic ones on the other hand. Serum total protein and globulin levels were decreased in diabetic rats and were increased in hypothyroid and diabetic hypothyroid rats. Hepatic total thiols and glutathione contents and catalase and peroxidase activity were profoundly decreased in diabetic rats while they (except glutathione) were increased in hypothyroid and diabetic hypothyroid rats. In conclusion, the hypothyroidism may have a counteracting effect on the hyperglycemic state and the elevated serum T4 level as well as the deteriorated antioxidant defense system found in diabetes mellitus, but both experimentally-induced diseases may synergize in inducing more elevation of serum total lipids, total cholesterol and LDL-cholesterol and more decrease in leptin levels.

Research paper thumbnail of Stem Cell Therapies in Regenerative Medicine and Diabetes Mellitus: Advances, Constraints and Future Prospects

Citation: Ahmed OM, Sayed HM. Stem Cell Therapies in Regenerative Medicine and Diabetes Mellitus:... more Citation: Ahmed OM, Sayed HM. Stem Cell Therapies in Regenerative Medicine and Diabetes Mellitus: Advances, Constraints and Future Prospects. J Transplant Stem Cel Biol. 2016;3(1): 22.

Research paper thumbnail of Stem Cell Therapies in Regenerative Medicine and Diabetes Mellitus: Advances, Constraints and Future Prospects

Stem cell therapy is one of the most promising treatments for the near future. This kind of thera... more Stem cell therapy is one of the most promising treatments for the near future. This kind of therapy can ameliorate or even reverse some diseases and have potential applications in regenerative and replacement medicines and diabetes mellitus. The different types of stem cells such as embryonic stem cells, induced pluripotent stem cells and adult stem cells have been proved to be operational in treating diabetes mellitus with clear limitations. The prevalence of diabetes mellitus type 1 and type 2 continues to rise and its complications are serious and may lead to death. The current treatment methods, other than stem cell therapy, do not treat the main causes of the disease and have many limitations. Although insulin injection is the standard therapy for type 1 diabetes mellitus, its exogenous injection cannot mimic insulin secretion from normal β-cells when blood glucose changes all the time. Thus, how to generate new β-cells is an important approach for the treatment of type 1 diabetes mellitus. Isolated islets are fragile and susceptible to pro-apoptotic factors and poorly proliferative. In contrast, mesenchymal stem cells (MSCs) are highly proliferative, anti-apoptotic and pluripotent to differentiate toward various cell types. The electrofusion between islets’ cells and MSCs produced fusion islets’ cells that are more resistant to apoptosis and are able to maintain insulin secretion for long periods. The stem cell therapy is also used for treatment of type 2 diabetes mellitus as well because the disease later progresses to β-cell dysfunction. Stem cell therapies were clinically applied for improvement of insulin sensitivity and metabolic control in long standing type 2 diabetes mellitus. In addition to the applications of stem cells in the cell therapy of diabetes mellitus, recent trends of studies tend to use the direct reprogrammed adult somatic cells especially endoderm-derived adult cells transdifferentiated into insulin secretory pancreatic β-cells. However, the use of stem cells especially human embryonic stem cells in research and therapy is subjected to limitations and constraints in many countries due to ethical and religious concerns. In this article, the types of stem cells and their resources and to what extent stem cell research can lead to progresses in regenerative medicine and diabetes mellitus therapies are reviewed. It also sheds light on ethical concerns and future hopes of stem cell use in research and therapy.

Research paper thumbnail of DADS Published article w volume and pages HepatomaRes1267-6673586_183215.pdf

Aim: This study was conducted to assess the in vivo and in vitro anti-tumor effects of diallyl di... more Aim: This study was conducted to assess the in vivo and in vitro anti-tumor effects of diallyl disulfi de (DADS) against Ehrlich ascites carcinoma (EAC) and to suggest its probable mechanism of action. Methods: EAC was induced in female mice by intraperitoneal injection of EAC-cells from stock mice. EAC-bearing mice were orally treated with 100 mg/kg body weight for 2 weeks beginning from the 1st day of EAC intraperitoneal transplantation. Cytotoxicity effects of DADS against EAC-cells in vitro were investigated at different concentrations (0, 6.25, 12.5, 25, 50, and 100 μg/mL) of DADS using trypan blue exclusion assay. Results: Data from this study exhibited a signifi cant decrease in EAC-aliquot volume as well as total and alive EAC-cell number and a marked increase in dead EAC-cell number and percent in EAC-bearing mice treated with DADS as compared with EAC-bearing control. These changes were consistent with increased number of cells which exhibited phenotypic apoptotic signs marked by a decrease in the expression of anti-apoptotic protein Bcl-2, an increase of pro-apoptotic and cell cycle arrest mediator p53 and an elevation of DNA fragmenting indicator terminal deoxynucleotidyl transferase in EAC-bearing mice treated with DADS. In addition, the tumor marker sialic acid level was markedly decreased in plasma and Ehrlich ascites in EAC-bearing mice treated with DADS. In vitro, DADS also produced anti-proliferative and anti-tumor cytotoxic potentials against EAC. Conclusion: DADS may have anti-cancer effects which may be mediated via modulation of apoptosis and cell cycle arrest.

Research paper thumbnail of BIOINFORMATICS ANALYSIS OF SOME FUNCTIONAL GENES AND PROTEINS INVOLVED IN OBESITY-INDUCED TYPE 2 DIABETES

The incidence of type-2 diabetes is rising rapidly worldwide, mainly because of the increase in t... more The incidence of type-2 diabetes is rising rapidly worldwide, mainly because of the increase in the incidence of obesity, which is an important risk factor for this condition. Both obesity and type-2 diabetes are complex genetic traits but they also share some nongenetic risk factors. Differences among individuals in their susceptibility to both these conditions probably reflect their genetic constitutions. The dramatic improvements in genomic and bioinformatic resources are accelerating the pace of gene discovery. It is tempting to speculate the key susceptible genes/proteins that bridges diabetes mellitus and obesity. In this regard, we evaluated the role of several genes/proteins that are believed to be involved in the evolution of obesity associated diabetes through thorough literature search. Also we analyzed the data pertaining to genes of these proteins extracted from the databases that are available online for free access. The functional cDNA sequences of these genes/proteins are extracted from National Center for Biotechnology Information (NCBI) and Ensembl Genome Browser. Our bioinformatic analysis reports 21 genes as ominous link with obesity associated diabetes. Also this study indicated that, adipose tissue is now known to express and secrete a variety of metabolites, hormones and cytokines that have been implicated in the development of insulin resistance.This bioinformatic study will be useful for future studies towards therapeutic inventions of obesity associated type-2 diabetes.

Research paper thumbnail of Ulva lactuca polysaccharides prevent wistar rat breast carci 022717

Background: Recently, several research studies have been focused on the isolation and function of... more Background: Recently, several research studies have been focused on the isolation and function of the polysaccharides derived from different algal species, which revealed multiple biological activities such as antioxidant and antitumor activities. This study assesses the possible breast cancer chemopreventive properties of common seaweeds, sea lettuce, Ulva lactuca (ulvan) polysaccharides using in vitro bioassays on human breast cancer cell line (MCF-7) and an in vivo animal model of breast carcinogenesis. Methods: Cytotoxic effect of ulvan polysaccharides on MCF-7 was tested in vitro. For an in vivo investigation, a single dose of 25 mg/kg body weight 7,12-dimethylbenz[a]anthracene (DMBA) and ulvan polysaccharides (50 mg/kg body weight every other day) for 10 weeks were administered orally to the Wistar rats. Results: Deleterious histopathological alterations in breast tissues including papillary cyst adenoma and hyperplasia of ductal epithelial lining with intraluminal necrotic materials and calcifications were observed in the DMBA-administered group. These lesions were prevented in the DMBA-administered group treated with ulvan polysaccharides. The immunohistochemical sections depicted that the treatment of DMBA-administered rats with ulvan polysaccharides markedly increased the lowered pro-apoptotic protein, p53, and decreased the elevated anti-apoptotic marker, bcl2, expression in the breast tissue. The elevated lipid peroxidation and the suppressed antioxidant enzyme activities in DMBA-administered control were significantly prevented by the treatment with ulvan polysaccharides. The elevated levels of inflammatory cytokines tumor necrosis factor-α and nitric oxide were significantly ameliorated in DMBA-administered rats treated with ulvan polysaccharides as compared to DMBA-administered control. Conclusion: In conclusion, ulvan polysaccharides at the level of initiation and promotion might have potential chemopreventive effects against breast carcinogenesis. These preventive effects may be mediated through the augmentation of apoptosis, suppression of oxidative stress and inflammation, and enhancement of antioxidant defense system.

Research paper thumbnail of Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity

Adipokines are bioactive molecules that regulate several physiological functions such as energy b... more Adipokines are bioactive molecules that regulate several physiological functions such as energy balance, insulin sensitization, appetite regulation, inflammatory response, and vascular homeostasis. They include proinflammatory cytokines such as adipocyte fatty acid binding protein (A-FABP) and anti-inflammatory cytokines such as adiponectin, as well as vasodilator and vasoconstrictor molecules. In obesity and type II diabetes mellitus (DM), insulin resistance causes impairment of the endocrine function of the perivascular adipose tissue, an imbalance in the secretion of vasoconstrictor and vasodilator molecules, and an increased production of reactive oxygen species. Recent studies have shown that targeting plasma levels of adipokines or the expression of their receptors can increase insulin sensitivity, improve vascular function, and reduce the risk of cardiovascular morbidity and mortality. Several reviews have discussed the potential of adipokines as therapeutic targets for type II DM and obesity; however, this review is the first to focus on their therapeutic potential for vascular dysfunction in type II DM and obesity.

Research paper thumbnail of Relationships between Oxidative Stress, Cancer Development and Therapeutic Interventions Cancer Development and Therapeutic Interventions