Afaf A Ain-Shoka - Academia.edu (original) (raw)
Papers by Afaf A Ain-Shoka
Journal of Clinical Investigation, 1981
measuring antigen-induced release of slow reacting substance of anaphylaxis and histamine from mi... more measuring antigen-induced release of slow reacting substance of anaphylaxis and histamine from minced lung, virus infection did not alter the sensitivity or the maximum effects of ovalbumin. Also, the ability of sulfonterol to inhibit the release of slow reacting substance of anaphylaxis and histamine was not affected by virus infection. These results demonstrate that infection of guinea pigs with respiratory virus results in a selective blockade of the beta adrenergic-mediated inhibition of antigen-induced contraction of airway smooth muscle. The guinea pig may serve as a useful model in physiological studies of virus-induced asthma.
QJM: An International Journal of Medicine, 2020
Background gastroesophageal reflux disease (GERD) is increasingly prevalent and costly, and it ma... more Background gastroesophageal reflux disease (GERD) is increasingly prevalent and costly, and it may affect as much as 20% of the western population. The pathophysiology of GERD is not due to acid overproduction but rather mechanical dysfunction centered around the lower esophageal sphincter (LES). Furthermore, the mainstay of GERD treatment, proton pump inhibitors (PPIs), have come under scrutiny because of worrisome side effects. Aim of the Work to prospectively compare between laparoscopic Nissen fundoplication and its Rossetti’s modification as anti-reflux procedures along with their operative and post-operative outcomes. Patients and Methods this is a prospective randomized study that was conducted on twenty (20) patients presenting to Ain-Shams University Hospitals in whom fundoplication was indicated for management of chronic GERD and was operated upon starting October 2016 to October 2018 with minimal follow up duration of one year. Results both procedures were nearly efficien...
Letters in Applied NanoBioScience, 2021
Increased fructose intake has been linked to the epidemiology of insulin resistance, type 2 diabe... more Increased fructose intake has been linked to the epidemiology of insulin resistance, type 2 diabetes mellitus, renal damage, and metabolic syndrome (MS). As oxidative stress plays a pivotal role in the pathology of insulin resistance, the present study was conducted to investigate the effects of Nigella Sativa (NS) and ginger as potent antioxidants on fructose-induced MS in rats. Male rats were fed with a high‐fructose high-fat-fed diet for 8 weeks. By the end of the 8th week, rats were divided into four groups; one was left untreated (normal control) and MS control group was treated with saline. MS groups were given Nigella sativa (4 ml/kg) and ginger (500 mg/kg) daily for 4 weeks. Markers chosen for assessment included the effect on body weight gain, glucose, insulin, adiponectin levels, and lipid profile. Also, protein expressions were estimated by glucose transporter 4 (GLUT4) content and peroxisome proliferator‐activated receptor‐gamma (PPARγ). Nigella sativa and ginger amelior...
Journal of Biochemical and Molecular Toxicology, 2021
The present study was conducted to investigate the potential adverse effect of Pb on pregnant Spr... more The present study was conducted to investigate the potential adverse effect of Pb on pregnant Sprague–Dawley rats and their fetuses after maternal exposure, on gestational days (GD) 7–16. The possible protective role of taurine (TA), administered throughout the gestation period (GD 1–20) against Pb toxicity, was also evaluated. Pregnant rats were divided into four groups: Group 1 (control) was given distilled water; Group 2 was exposed to Pb (250 ppm) in drinking water (GD 7–16), whereas Group 3 received TA (50 mg/kg/day) by oral gavage (GD 1–20); Group 4 was exposed to Pb (GD 7–16), whereas pretreated with TA from GD 1 till the end of the gestation period. After termination on GD 20, maternal and embryo‐fetal outcomes were evaluated. Blood samples were collected for hematological and biochemical parameters assessment. The results showed that, Pb induced a significant reduction in the maternal body weight, weight gain, uterine and placental weight, in addition to a high incidence of abortion and fetal resorption. Meanwhile, fetuses demonstrated decreased body weight and length, with a high rate of mortality as well as external and skeletal abnormalities. Additionally, Pb induced severe hematological and biochemical alterations in both dams and fetuses. The toxicity of Pb was further emphasized by placental histopathological examination and hepatic DNA fragmentation. Pretreatment with TA greatly attenuated the impact of Pb on both maternal and fetal parameters. Moreover, TA alleviated the incidence of placental damage and hepatic DNA fragmentation. The results highlight the potential prophylaxis role of TA against maternal and developmental Pb toxicity.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2020
Deregulated activity of protein kinase B/mammalian target of rapamycin complex-1 (Akt/mTORC1) inc... more Deregulated activity of protein kinase B/mammalian target of rapamycin complex-1 (Akt/mTORC1) incites crucial pathological characteristics of diabetic nephropathy. The acyclic monoterpene geraniol has been recently reported to possess antidiabetic effects; however, its potential renoprotective effect in diabetes has not yet been elucidated. This study aimed to assess the possible modulatory effect of geraniol on the Akt/mTORC1 pathway in diabetes-induced nephropathy in rats compared to the standard antidiabetic drug gliclazide. Geraniol and gliclazide was administered daily to diabetic rats for 6 weeks starting on the 3rd-day post diabetes induction by streptozotocin (STZ). Geraniol amended the deteriorated renal function (serum creatinine; blood urea nitrogen). It exerted a remarkable antihyperglycemic effect that is comparable to that of gliclazide and suppressed the fibrotic marker, transforming growth factor-β. Geraniol restored redox balance and inhibited lipid peroxidation by reducing nicotine amide adenine dinucleotide phosphate oxidase and enhancing the antioxidant enzyme, superoxide dismutase. These beneficial effects were associated with a robust downregulation of miRNA-21 and consequently, reversion of tumor suppressor protein phosphatase and tension homolog (PTEN)/Akt/mTORC1 cue and its downstream proteins required for mesangial cell proliferation and matrix protein synthesis. The current study indicates that geraniol interfered with miRNA-21/ PTEN/AKT/mTORC1 pathway signaling that contributes largely to the progression of mesangial expansion and extracellular matrix deposition in diabetic nephropathy.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2018
Selenium and its derivatives including sodium selenite (sod sel) belong to the group of essential... more Selenium and its derivatives including sodium selenite (sod sel) belong to the group of essential trace elements needed for proper health and nutrition. They are fairly safe and possess antioxidant and anti-inflammatory properties. The aim of present investigation was to elucidate the effect of sod sel on experimental colitis model in rats. Colitis was induced by intrarectal instillation of 4% (v/v) acetic acid. Two hours later, sod sel was given to rats on a daily basis for 15 consecutive days. Clinical symptoms, colon mass index, spleen weight inflammatory markers, hematological, biochemical, macroscopic, and histological changes were determined. Sod sel markedly ameliorated colitis as evidenced by a significant decrease in macroscopic and microscopic score, disease activity index, colon mass index, and spleen weight. Treatment with sod sel attenuated oxidative stress in the colon by normalizing the colonic content of nitric oxide, malondialdehyde, and reduced glutathione, as well as the activities of catalase, superoxide dismutase, and junctional adhesion molecule (JAM-a). In addition, it significantly reduced colonic myeloperoxidase content, the intercellular adhesion molecule (ICAM-1), and the proinflammatory cytokines; TNF-α, IL-1β. Moreover, sod sel normalized hematological parameters, serum transaminases, and kidney and liver function enzymes. The current study indicates that sod sel was effective in ameliorating the intestinal and extra-intestinal manifestation in acetic acid-induced colitis through its antioxidant, anti-inflammatory, and immunomodulatory effects.
Inflammation, Jan 4, 2017
Sepsis is a systemic inflammatory disorder which often occurs during extremely stressful conditio... more Sepsis is a systemic inflammatory disorder which often occurs during extremely stressful conditions such as trauma, burn, shock, and infection. This study investigated the curative effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) against hepatic, renal, and pulmonary responses caused by a single administration of lipopolysaccharide (LPS) (10 mg/kg, i.p) in rats. Treatment with BM-MSCs (5 × 10in 0.1 ml PBS, i.p.) 3 h after LPS antagonized the LPS-induced increment of the liver enzymes (ALT, AST) and kidney functions (BUN, sCr). BM-MSCs decreased tissue levels of P38-MAPK, NF-κB, STAT-3, TNF-α, IL-1β, iNOS, Bax together with elevation of the anti-inflammatory cytokine IL-10 and the anti-apoptotic biomarker Bcl-2. Meanwhile, rats exhibited marked reduction of the broncho-alveolar lavage fluid levels of TNF-α, IL-1β, and IFN-γ. Interestingly, BM-MSCs normalized both broncho-alveolar lavage fluid (BALF) neutrophils count and lung wet/dry ratios. Briefly, these findings may...
Chemotherapy, 2009
Access to full text and tables of contents, including tentative ones for forthcoming issues: www.... more Access to full text and tables of contents, including tentative ones for forthcoming issues: www.karger.com/che_issues 270 Assessment of the in vitro Efficacy of the Novel Antimicrobial Peptide CECT7121 against Human Gram-Positive Bacteria from Serious Infections Refractory to Treatment Sparo, M.D. (Tandil); Jones, D.G. (Penicuik); Sánchez Bruni, S.F.
Clinical Therapeutics, 2015
e49 lead to nephrotoxicity and ototoxicity. However, in SDD, tobramycin suspension is given orall... more e49 lead to nephrotoxicity and ototoxicity. However, in SDD, tobramycin suspension is given orally and aminoglycosides are not absorbed via the gut. Therefore, SDD will, generally, not lead to systemic exposure. However, we describe a patient with Graft Versus Host Disease (GVHD) who developed toxic tobramycin levels. Methods: In this case report, we describe a 34 year old male patient with Acute Myeloid Leukemia. After allogenic stem cell transplantation he developed GVHD of the intestines, amongst all leading to severe diarrhea. Previously, several ICU patients with SDD and GVHD developed systemic tobramycin exposure. Therefore, tobramycin levels were measured by means of EMIT Immunoassay (Architect, Abbott). Results: After use of 8 times a day 80 mg tobramycin orally for 30 days, his tobramycin trough level was 3.5 mg/L (reference < 0.5 mg/L). His creatinine was 102 μ mol/L and urea was 23.1 mmol/L (increase > 20% last 4 days). Tobramycin was stopped and levels dropped to 0.87 mg/L after 2 days and 0.22 mg/L after 4 days. Tobramycin was started again in a regimen of 4 times a day 80 mg tobramycin orally, under daily monitoring of tobramycin levels. Creatinine and urea recovered. High tobramycin levels were contributed to systemic leakage of tobramycin via the intestines. Conclusion: In SDD, tobramycin is normally not absorbed. However, in severe intestine GVHD, systemic absorption of tobramycin can occur. In this patient toxic tobramycin levels were combined with impaired renal function. In patients with GVHD of the intestines and frequent administration of tobramycin-containing SDD frequent monitoring of tobramycin levels is recommended.
Journal of Hepatology, 2015
Pharmacological Reports, 2015
Background: Recent growing consensus introduced thiazolidinediones, agonists of the nuclear recep... more Background: Recent growing consensus introduced thiazolidinediones, agonists of the nuclear receptor peroxisome proliferator-activated receptor gamma as promising candidates in the management of ischemia in various organs. Thereby, interest was raised to investigate the neuroprotective effects of pioglitazone against transient ischemia/reperfusion (I/R) injury in diabetic rats targeting mainly the oxidative-inflammatory-apoptotic cascades which are involved in this insult. Methods: Forebrain ischemia was induced in streptozotocin-diabetic rats by occlusion of the bilateral common carotid arteries for 15 min followed by 1 h reperfusion. Pioglitazone (10 mg/kg; po) was administered daily for 2 weeks prior to I/R. Results: The drug alleviated hippocampal injury inflicted by diabetes and/or I/R injury where it suppressed nuclear factor kappa (NFkB), and consequently the downstream inflammatory cytokines tumor necrosis factor-a and interleukin-6. In parallel, the anti-inflammatory cytokine interleukin-10 was elevated. Antioxidant potential of pioglitazone was depicted, where it reduced neutrophil infiltration, lipid peroxides, nitric oxide associated with replenished reduced glutathione. Decline of excitatory amino acid glutamate content is a main finding which is probably mediated by the NFkB signaling pathway as well as improved oxidant status. Pioglitazone exerted an anti-apoptotic effect as reflected by the reduction of the cytosolic cytochrome c and the key downstream executioner caspase-3. Conclusions: Pioglitazone is endowed with neuroprotective properties which are probably mediated by its antioxidant, anti-inflammatory, and anti-apoptotic mechanisms hence may provide a successful agent for the management of ischemic stroke.
Annals of Nutrition and Metabolism, 2009
Environmental science and pollution research international, Jan 15, 2018
The present study was conducted to evaluate the possible protective role of the algae spirulina (... more The present study was conducted to evaluate the possible protective role of the algae spirulina (Sp) against nephrotoxicity and oxidative stress which are the main secondary effects induced by the immunosuppressant drug CSA and/or ionizing radiation. In this study, male rats were given Sp (1 g/kg) either for 15 days before irradiation (6.5 Gy) or 5 days before and 10 days concomitant with CSA (25 mg/kg). Markers used to assess renal injury included serum creatinine, urea, glucose, albumin, protein, and lipid profile as well as kidney content of reduced glutathione (GSH); lipid peroxidation (thiobarbituric acid reactive substances (TBARS)); nitrite and superoxide dismutase (SOD) activity. In addition, some trace elements (Zn and Mg) were estimated in kidney. Apoptosis was assessed by immunohistochemical estimation of caspase-3 expression in addition to histopathological examination. Results revealed that gamma radiation and/or CSA induced elevation in urea, creatinine, lipids, and gl...
Inflammation, 2017
Sepsis caused by lipopolysaccharide (LPS) is a life-threatening disease accompanied by multiple o... more Sepsis caused by lipopolysaccharide (LPS) is a life-threatening disease accompanied by multiple organ failure. This study investigated the curative effects of imatinib (IMA) against hepatic, renal, and pulmonary responses caused by a single administration of LPS (10 mg/kg, i.p.) in rats. Treatment with IMA (15 mg/kg, i.p.) 30 min after LPS antagonized the LPS-induced boost of liver enzymes (ALT, AST), kidney functions (BUN, sCr) as well as the elevated pulmonary vascular permeability and edema. IMA declined tissue contents of NF-κB, STAT-3, P38-MAPK, TNF-α, IL-1β, and iNOS. It also amplified the antiinflammatory cytokine IL-10 as well as the Bcl-2/Bax ratio, a cardinal indicator of the antiapoptotic effect. Meanwhile, the rats exhibited marked reduction of the broncho-alveolar lavage fluid (BALF) contents of TNF-α, IL-1β, IFN-γ, and neutrophil count; however, they revealed prominent augmentation of the BALF content IL-10. In conclusion, these findings suggest that IMA is endowed with anti-inflammatory, anti-oxidant, and anti-apoptotic properties and hence may provide a novel agent for the management of sepsis.
Journal of Biochemical and Molecular Toxicology, 2018
Peptic ulcer is a common disorder of the stomach and duodenum. Herbs and medicinal plants are con... more Peptic ulcer is a common disorder of the stomach and duodenum. Herbs and medicinal plants are considered to be a potential source to combat various diseases including gastric ulcer. The present study was conducted to evaluate the gastro protective effects of Echinacea extract, Green tea extract and Boswellia extract on a pyloric ligation-induced gastric ulcer. Six groups of rats were intraperitoneally pre-treated with saline as normal group, saline as ulcer group, 20 mg/kg of ranitidine as positive group, Echinacea extract (25 mg/kg, I.P), Green tea extract (25 mg/kg, I.P) and Boswellia extract (200 mg/kg, I.P) for 15 consecutive days before pyloric ligation. Gastric acidity, ulcer index and histology were assessed. Gastric homogenates were determined for Malondialdehyde (MDA) content, Glutathione (GSH) content in addition to blood Superoxide Dismutase (SOD) activity. Pyloric ligation elevated gastric acidity, ulcer index and malondialdehyde content, while glutathione content and su...
Life Sciences, 2015
Aims: Ischemic stroke is a major macrovascular complication of diabetes mellitus. Sitagliptin, a ... more Aims: Ischemic stroke is a major macrovascular complication of diabetes mellitus. Sitagliptin, a dipeptidyl peptidase-IV inhibitor, was recently shown to improve cognitive functions in diabetic rats; hence the present study was conducted to evaluate its protective effect against transient ischemia-reperfusion (I/R) in diabetic animals. Main methods: Diabetes was induced by streptozotocin (40 mg/kg). Six weeks later, cerebral I/R was induced by bicommon carotid occlusion for 15 min followed by 1 h reperfusion. Sitagliptin (250 mg/kg; p.o.) was administered daily during the last 2 weeks before I/R. Key findings: The drug alleviated hippocampal injury inflicted by diabetes and/or I/R injury where it suppressed nuclear factor kappa Q4 (NF-κ)B, and consequently the downstream inflammatory cytokines tumor necrosis factorα and interleukin-6. In parallel, the anti-inflammatory cytokine interleukin-10 was elevated. Antioxidant potential of sitagliptin was depicted, where it reduced neutrophil infiltration, lipid peroxides and nitric oxide associated with replenished reduced glutathione. Decline of excitatory amino acid glutamate content is a main finding which is probably mediated by the NF-kB signaling pathway as well as improved oxidant status. Sitagliptin exerted an anti-apoptotic effect as reflected by the reduction of the mitochondrial matrix component Q5 cytochrome c and the key downstream executioner caspase-3. Histopathological examination corroborated the biochemical data. Significance: These findings suggest that sitagliptin is endowed with neuroprotective properties which are probably mediated by its antioxidant, anti-inflammatory, and anti-apoptotic mechanisms and hence may provide a novel agent for the management of ischemic stroke in diabetics. 37
Bulletin of Faculty of Pharmacy, Cairo University, 2016
BMC cancer, 2016
The link between inflammation and cancer has been confirmed by the use of anti-inflammatory thera... more The link between inflammation and cancer has been confirmed by the use of anti-inflammatory therapies in cancer prevention and treatment. 5-aminosalicylic acid (5-ASA) was shown to decrease the growth and survival of colorectal cancer (CRC) cells. Studies also revealed that metformin induced apoptosis in several cancer cell lines. We investigated the combinatory effect of 5-ASA and metformin on HCT-116 and Caco-2 CRC cell lines. Apoptotic markers were determined using western blotting. Expression of pro-inflammatory cytokines was determined by RT-PCR. Inflammatory transcription factors and metastatic markers were measured by ELISA. Metformin enhanced CRC cell death induced by 5-ASA through significant increase in oxidative stress and activation of apoptotic machinery. Moreover, metformin enhanced the anti-inflammatory effect of 5-ASA by decreasing the gene expression of IL-1β, IL-6, COX-2 and TNF-α and its receptors; TNF-R1 and TNF-R2. Significant inhibition of activation of NF-κB a...
Research in pharmaceutical sciences
The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased, especially in... more The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased, especially in patients exhibit one or more features of the metabolic syndrome. This study investigates the effect of rosuvastatin (RSV) and/or β-carotene (βC) in NAFLD-induced rats. Rats were classified into nine groups; normal (I), NAFLD-induced with high-fat diet (HFD; II), NAFLD switched to regular diet (RD; III), NAFLD-HFD or NAFLD-RD treated with RSV (IV, V), βC (VI, VII) or both RSV+βC (VIII, IX), respectively. After four weeks, rats were sacrificed to obtain serum samples and liver tissues. Liver histology, lipid profile, liver oxidative stress markers, and adipocytokines were measured. Liver sections of rats with NAFLD-HFD revealed steatosis, lose of hepatic architecture, inflammation and hepatocyte vacuolation with high percentage of cell fibrosis. Serum levels of ALT, AST, ALP, gamma glutamyl transferase (GGT) and lipid profile (triglycerides, cholesterol, LDL and VLDL) were significantly i...
Journal of Clinical Investigation, 1981
measuring antigen-induced release of slow reacting substance of anaphylaxis and histamine from mi... more measuring antigen-induced release of slow reacting substance of anaphylaxis and histamine from minced lung, virus infection did not alter the sensitivity or the maximum effects of ovalbumin. Also, the ability of sulfonterol to inhibit the release of slow reacting substance of anaphylaxis and histamine was not affected by virus infection. These results demonstrate that infection of guinea pigs with respiratory virus results in a selective blockade of the beta adrenergic-mediated inhibition of antigen-induced contraction of airway smooth muscle. The guinea pig may serve as a useful model in physiological studies of virus-induced asthma.
QJM: An International Journal of Medicine, 2020
Background gastroesophageal reflux disease (GERD) is increasingly prevalent and costly, and it ma... more Background gastroesophageal reflux disease (GERD) is increasingly prevalent and costly, and it may affect as much as 20% of the western population. The pathophysiology of GERD is not due to acid overproduction but rather mechanical dysfunction centered around the lower esophageal sphincter (LES). Furthermore, the mainstay of GERD treatment, proton pump inhibitors (PPIs), have come under scrutiny because of worrisome side effects. Aim of the Work to prospectively compare between laparoscopic Nissen fundoplication and its Rossetti’s modification as anti-reflux procedures along with their operative and post-operative outcomes. Patients and Methods this is a prospective randomized study that was conducted on twenty (20) patients presenting to Ain-Shams University Hospitals in whom fundoplication was indicated for management of chronic GERD and was operated upon starting October 2016 to October 2018 with minimal follow up duration of one year. Results both procedures were nearly efficien...
Letters in Applied NanoBioScience, 2021
Increased fructose intake has been linked to the epidemiology of insulin resistance, type 2 diabe... more Increased fructose intake has been linked to the epidemiology of insulin resistance, type 2 diabetes mellitus, renal damage, and metabolic syndrome (MS). As oxidative stress plays a pivotal role in the pathology of insulin resistance, the present study was conducted to investigate the effects of Nigella Sativa (NS) and ginger as potent antioxidants on fructose-induced MS in rats. Male rats were fed with a high‐fructose high-fat-fed diet for 8 weeks. By the end of the 8th week, rats were divided into four groups; one was left untreated (normal control) and MS control group was treated with saline. MS groups were given Nigella sativa (4 ml/kg) and ginger (500 mg/kg) daily for 4 weeks. Markers chosen for assessment included the effect on body weight gain, glucose, insulin, adiponectin levels, and lipid profile. Also, protein expressions were estimated by glucose transporter 4 (GLUT4) content and peroxisome proliferator‐activated receptor‐gamma (PPARγ). Nigella sativa and ginger amelior...
Journal of Biochemical and Molecular Toxicology, 2021
The present study was conducted to investigate the potential adverse effect of Pb on pregnant Spr... more The present study was conducted to investigate the potential adverse effect of Pb on pregnant Sprague–Dawley rats and their fetuses after maternal exposure, on gestational days (GD) 7–16. The possible protective role of taurine (TA), administered throughout the gestation period (GD 1–20) against Pb toxicity, was also evaluated. Pregnant rats were divided into four groups: Group 1 (control) was given distilled water; Group 2 was exposed to Pb (250 ppm) in drinking water (GD 7–16), whereas Group 3 received TA (50 mg/kg/day) by oral gavage (GD 1–20); Group 4 was exposed to Pb (GD 7–16), whereas pretreated with TA from GD 1 till the end of the gestation period. After termination on GD 20, maternal and embryo‐fetal outcomes were evaluated. Blood samples were collected for hematological and biochemical parameters assessment. The results showed that, Pb induced a significant reduction in the maternal body weight, weight gain, uterine and placental weight, in addition to a high incidence of abortion and fetal resorption. Meanwhile, fetuses demonstrated decreased body weight and length, with a high rate of mortality as well as external and skeletal abnormalities. Additionally, Pb induced severe hematological and biochemical alterations in both dams and fetuses. The toxicity of Pb was further emphasized by placental histopathological examination and hepatic DNA fragmentation. Pretreatment with TA greatly attenuated the impact of Pb on both maternal and fetal parameters. Moreover, TA alleviated the incidence of placental damage and hepatic DNA fragmentation. The results highlight the potential prophylaxis role of TA against maternal and developmental Pb toxicity.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2020
Deregulated activity of protein kinase B/mammalian target of rapamycin complex-1 (Akt/mTORC1) inc... more Deregulated activity of protein kinase B/mammalian target of rapamycin complex-1 (Akt/mTORC1) incites crucial pathological characteristics of diabetic nephropathy. The acyclic monoterpene geraniol has been recently reported to possess antidiabetic effects; however, its potential renoprotective effect in diabetes has not yet been elucidated. This study aimed to assess the possible modulatory effect of geraniol on the Akt/mTORC1 pathway in diabetes-induced nephropathy in rats compared to the standard antidiabetic drug gliclazide. Geraniol and gliclazide was administered daily to diabetic rats for 6 weeks starting on the 3rd-day post diabetes induction by streptozotocin (STZ). Geraniol amended the deteriorated renal function (serum creatinine; blood urea nitrogen). It exerted a remarkable antihyperglycemic effect that is comparable to that of gliclazide and suppressed the fibrotic marker, transforming growth factor-β. Geraniol restored redox balance and inhibited lipid peroxidation by reducing nicotine amide adenine dinucleotide phosphate oxidase and enhancing the antioxidant enzyme, superoxide dismutase. These beneficial effects were associated with a robust downregulation of miRNA-21 and consequently, reversion of tumor suppressor protein phosphatase and tension homolog (PTEN)/Akt/mTORC1 cue and its downstream proteins required for mesangial cell proliferation and matrix protein synthesis. The current study indicates that geraniol interfered with miRNA-21/ PTEN/AKT/mTORC1 pathway signaling that contributes largely to the progression of mesangial expansion and extracellular matrix deposition in diabetic nephropathy.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2018
Selenium and its derivatives including sodium selenite (sod sel) belong to the group of essential... more Selenium and its derivatives including sodium selenite (sod sel) belong to the group of essential trace elements needed for proper health and nutrition. They are fairly safe and possess antioxidant and anti-inflammatory properties. The aim of present investigation was to elucidate the effect of sod sel on experimental colitis model in rats. Colitis was induced by intrarectal instillation of 4% (v/v) acetic acid. Two hours later, sod sel was given to rats on a daily basis for 15 consecutive days. Clinical symptoms, colon mass index, spleen weight inflammatory markers, hematological, biochemical, macroscopic, and histological changes were determined. Sod sel markedly ameliorated colitis as evidenced by a significant decrease in macroscopic and microscopic score, disease activity index, colon mass index, and spleen weight. Treatment with sod sel attenuated oxidative stress in the colon by normalizing the colonic content of nitric oxide, malondialdehyde, and reduced glutathione, as well as the activities of catalase, superoxide dismutase, and junctional adhesion molecule (JAM-a). In addition, it significantly reduced colonic myeloperoxidase content, the intercellular adhesion molecule (ICAM-1), and the proinflammatory cytokines; TNF-α, IL-1β. Moreover, sod sel normalized hematological parameters, serum transaminases, and kidney and liver function enzymes. The current study indicates that sod sel was effective in ameliorating the intestinal and extra-intestinal manifestation in acetic acid-induced colitis through its antioxidant, anti-inflammatory, and immunomodulatory effects.
Inflammation, Jan 4, 2017
Sepsis is a systemic inflammatory disorder which often occurs during extremely stressful conditio... more Sepsis is a systemic inflammatory disorder which often occurs during extremely stressful conditions such as trauma, burn, shock, and infection. This study investigated the curative effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) against hepatic, renal, and pulmonary responses caused by a single administration of lipopolysaccharide (LPS) (10 mg/kg, i.p) in rats. Treatment with BM-MSCs (5 × 10in 0.1 ml PBS, i.p.) 3 h after LPS antagonized the LPS-induced increment of the liver enzymes (ALT, AST) and kidney functions (BUN, sCr). BM-MSCs decreased tissue levels of P38-MAPK, NF-κB, STAT-3, TNF-α, IL-1β, iNOS, Bax together with elevation of the anti-inflammatory cytokine IL-10 and the anti-apoptotic biomarker Bcl-2. Meanwhile, rats exhibited marked reduction of the broncho-alveolar lavage fluid levels of TNF-α, IL-1β, and IFN-γ. Interestingly, BM-MSCs normalized both broncho-alveolar lavage fluid (BALF) neutrophils count and lung wet/dry ratios. Briefly, these findings may...
Chemotherapy, 2009
Access to full text and tables of contents, including tentative ones for forthcoming issues: www.... more Access to full text and tables of contents, including tentative ones for forthcoming issues: www.karger.com/che_issues 270 Assessment of the in vitro Efficacy of the Novel Antimicrobial Peptide CECT7121 against Human Gram-Positive Bacteria from Serious Infections Refractory to Treatment Sparo, M.D. (Tandil); Jones, D.G. (Penicuik); Sánchez Bruni, S.F.
Clinical Therapeutics, 2015
e49 lead to nephrotoxicity and ototoxicity. However, in SDD, tobramycin suspension is given orall... more e49 lead to nephrotoxicity and ototoxicity. However, in SDD, tobramycin suspension is given orally and aminoglycosides are not absorbed via the gut. Therefore, SDD will, generally, not lead to systemic exposure. However, we describe a patient with Graft Versus Host Disease (GVHD) who developed toxic tobramycin levels. Methods: In this case report, we describe a 34 year old male patient with Acute Myeloid Leukemia. After allogenic stem cell transplantation he developed GVHD of the intestines, amongst all leading to severe diarrhea. Previously, several ICU patients with SDD and GVHD developed systemic tobramycin exposure. Therefore, tobramycin levels were measured by means of EMIT Immunoassay (Architect, Abbott). Results: After use of 8 times a day 80 mg tobramycin orally for 30 days, his tobramycin trough level was 3.5 mg/L (reference < 0.5 mg/L). His creatinine was 102 μ mol/L and urea was 23.1 mmol/L (increase > 20% last 4 days). Tobramycin was stopped and levels dropped to 0.87 mg/L after 2 days and 0.22 mg/L after 4 days. Tobramycin was started again in a regimen of 4 times a day 80 mg tobramycin orally, under daily monitoring of tobramycin levels. Creatinine and urea recovered. High tobramycin levels were contributed to systemic leakage of tobramycin via the intestines. Conclusion: In SDD, tobramycin is normally not absorbed. However, in severe intestine GVHD, systemic absorption of tobramycin can occur. In this patient toxic tobramycin levels were combined with impaired renal function. In patients with GVHD of the intestines and frequent administration of tobramycin-containing SDD frequent monitoring of tobramycin levels is recommended.
Journal of Hepatology, 2015
Pharmacological Reports, 2015
Background: Recent growing consensus introduced thiazolidinediones, agonists of the nuclear recep... more Background: Recent growing consensus introduced thiazolidinediones, agonists of the nuclear receptor peroxisome proliferator-activated receptor gamma as promising candidates in the management of ischemia in various organs. Thereby, interest was raised to investigate the neuroprotective effects of pioglitazone against transient ischemia/reperfusion (I/R) injury in diabetic rats targeting mainly the oxidative-inflammatory-apoptotic cascades which are involved in this insult. Methods: Forebrain ischemia was induced in streptozotocin-diabetic rats by occlusion of the bilateral common carotid arteries for 15 min followed by 1 h reperfusion. Pioglitazone (10 mg/kg; po) was administered daily for 2 weeks prior to I/R. Results: The drug alleviated hippocampal injury inflicted by diabetes and/or I/R injury where it suppressed nuclear factor kappa (NFkB), and consequently the downstream inflammatory cytokines tumor necrosis factor-a and interleukin-6. In parallel, the anti-inflammatory cytokine interleukin-10 was elevated. Antioxidant potential of pioglitazone was depicted, where it reduced neutrophil infiltration, lipid peroxides, nitric oxide associated with replenished reduced glutathione. Decline of excitatory amino acid glutamate content is a main finding which is probably mediated by the NFkB signaling pathway as well as improved oxidant status. Pioglitazone exerted an anti-apoptotic effect as reflected by the reduction of the cytosolic cytochrome c and the key downstream executioner caspase-3. Conclusions: Pioglitazone is endowed with neuroprotective properties which are probably mediated by its antioxidant, anti-inflammatory, and anti-apoptotic mechanisms hence may provide a successful agent for the management of ischemic stroke.
Annals of Nutrition and Metabolism, 2009
Environmental science and pollution research international, Jan 15, 2018
The present study was conducted to evaluate the possible protective role of the algae spirulina (... more The present study was conducted to evaluate the possible protective role of the algae spirulina (Sp) against nephrotoxicity and oxidative stress which are the main secondary effects induced by the immunosuppressant drug CSA and/or ionizing radiation. In this study, male rats were given Sp (1 g/kg) either for 15 days before irradiation (6.5 Gy) or 5 days before and 10 days concomitant with CSA (25 mg/kg). Markers used to assess renal injury included serum creatinine, urea, glucose, albumin, protein, and lipid profile as well as kidney content of reduced glutathione (GSH); lipid peroxidation (thiobarbituric acid reactive substances (TBARS)); nitrite and superoxide dismutase (SOD) activity. In addition, some trace elements (Zn and Mg) were estimated in kidney. Apoptosis was assessed by immunohistochemical estimation of caspase-3 expression in addition to histopathological examination. Results revealed that gamma radiation and/or CSA induced elevation in urea, creatinine, lipids, and gl...
Inflammation, 2017
Sepsis caused by lipopolysaccharide (LPS) is a life-threatening disease accompanied by multiple o... more Sepsis caused by lipopolysaccharide (LPS) is a life-threatening disease accompanied by multiple organ failure. This study investigated the curative effects of imatinib (IMA) against hepatic, renal, and pulmonary responses caused by a single administration of LPS (10 mg/kg, i.p.) in rats. Treatment with IMA (15 mg/kg, i.p.) 30 min after LPS antagonized the LPS-induced boost of liver enzymes (ALT, AST), kidney functions (BUN, sCr) as well as the elevated pulmonary vascular permeability and edema. IMA declined tissue contents of NF-κB, STAT-3, P38-MAPK, TNF-α, IL-1β, and iNOS. It also amplified the antiinflammatory cytokine IL-10 as well as the Bcl-2/Bax ratio, a cardinal indicator of the antiapoptotic effect. Meanwhile, the rats exhibited marked reduction of the broncho-alveolar lavage fluid (BALF) contents of TNF-α, IL-1β, IFN-γ, and neutrophil count; however, they revealed prominent augmentation of the BALF content IL-10. In conclusion, these findings suggest that IMA is endowed with anti-inflammatory, anti-oxidant, and anti-apoptotic properties and hence may provide a novel agent for the management of sepsis.
Journal of Biochemical and Molecular Toxicology, 2018
Peptic ulcer is a common disorder of the stomach and duodenum. Herbs and medicinal plants are con... more Peptic ulcer is a common disorder of the stomach and duodenum. Herbs and medicinal plants are considered to be a potential source to combat various diseases including gastric ulcer. The present study was conducted to evaluate the gastro protective effects of Echinacea extract, Green tea extract and Boswellia extract on a pyloric ligation-induced gastric ulcer. Six groups of rats were intraperitoneally pre-treated with saline as normal group, saline as ulcer group, 20 mg/kg of ranitidine as positive group, Echinacea extract (25 mg/kg, I.P), Green tea extract (25 mg/kg, I.P) and Boswellia extract (200 mg/kg, I.P) for 15 consecutive days before pyloric ligation. Gastric acidity, ulcer index and histology were assessed. Gastric homogenates were determined for Malondialdehyde (MDA) content, Glutathione (GSH) content in addition to blood Superoxide Dismutase (SOD) activity. Pyloric ligation elevated gastric acidity, ulcer index and malondialdehyde content, while glutathione content and su...
Life Sciences, 2015
Aims: Ischemic stroke is a major macrovascular complication of diabetes mellitus. Sitagliptin, a ... more Aims: Ischemic stroke is a major macrovascular complication of diabetes mellitus. Sitagliptin, a dipeptidyl peptidase-IV inhibitor, was recently shown to improve cognitive functions in diabetic rats; hence the present study was conducted to evaluate its protective effect against transient ischemia-reperfusion (I/R) in diabetic animals. Main methods: Diabetes was induced by streptozotocin (40 mg/kg). Six weeks later, cerebral I/R was induced by bicommon carotid occlusion for 15 min followed by 1 h reperfusion. Sitagliptin (250 mg/kg; p.o.) was administered daily during the last 2 weeks before I/R. Key findings: The drug alleviated hippocampal injury inflicted by diabetes and/or I/R injury where it suppressed nuclear factor kappa Q4 (NF-κ)B, and consequently the downstream inflammatory cytokines tumor necrosis factorα and interleukin-6. In parallel, the anti-inflammatory cytokine interleukin-10 was elevated. Antioxidant potential of sitagliptin was depicted, where it reduced neutrophil infiltration, lipid peroxides and nitric oxide associated with replenished reduced glutathione. Decline of excitatory amino acid glutamate content is a main finding which is probably mediated by the NF-kB signaling pathway as well as improved oxidant status. Sitagliptin exerted an anti-apoptotic effect as reflected by the reduction of the mitochondrial matrix component Q5 cytochrome c and the key downstream executioner caspase-3. Histopathological examination corroborated the biochemical data. Significance: These findings suggest that sitagliptin is endowed with neuroprotective properties which are probably mediated by its antioxidant, anti-inflammatory, and anti-apoptotic mechanisms and hence may provide a novel agent for the management of ischemic stroke in diabetics. 37
Bulletin of Faculty of Pharmacy, Cairo University, 2016
BMC cancer, 2016
The link between inflammation and cancer has been confirmed by the use of anti-inflammatory thera... more The link between inflammation and cancer has been confirmed by the use of anti-inflammatory therapies in cancer prevention and treatment. 5-aminosalicylic acid (5-ASA) was shown to decrease the growth and survival of colorectal cancer (CRC) cells. Studies also revealed that metformin induced apoptosis in several cancer cell lines. We investigated the combinatory effect of 5-ASA and metformin on HCT-116 and Caco-2 CRC cell lines. Apoptotic markers were determined using western blotting. Expression of pro-inflammatory cytokines was determined by RT-PCR. Inflammatory transcription factors and metastatic markers were measured by ELISA. Metformin enhanced CRC cell death induced by 5-ASA through significant increase in oxidative stress and activation of apoptotic machinery. Moreover, metformin enhanced the anti-inflammatory effect of 5-ASA by decreasing the gene expression of IL-1β, IL-6, COX-2 and TNF-α and its receptors; TNF-R1 and TNF-R2. Significant inhibition of activation of NF-κB a...
Research in pharmaceutical sciences
The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased, especially in... more The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased, especially in patients exhibit one or more features of the metabolic syndrome. This study investigates the effect of rosuvastatin (RSV) and/or β-carotene (βC) in NAFLD-induced rats. Rats were classified into nine groups; normal (I), NAFLD-induced with high-fat diet (HFD; II), NAFLD switched to regular diet (RD; III), NAFLD-HFD or NAFLD-RD treated with RSV (IV, V), βC (VI, VII) or both RSV+βC (VIII, IX), respectively. After four weeks, rats were sacrificed to obtain serum samples and liver tissues. Liver histology, lipid profile, liver oxidative stress markers, and adipocytokines were measured. Liver sections of rats with NAFLD-HFD revealed steatosis, lose of hepatic architecture, inflammation and hepatocyte vacuolation with high percentage of cell fibrosis. Serum levels of ALT, AST, ALP, gamma glutamyl transferase (GGT) and lipid profile (triglycerides, cholesterol, LDL and VLDL) were significantly i...