Professor Saeed Alghamdi | Umm Al-Qura University, Makkah, Saudi Arabia (original) (raw)

Papers by Professor Saeed Alghamdi

Anxiety and depression are highly comorbid disorders possibly sharing a common neurobiological m... more Anxiety and depression are highly comorbid disorders possibly sharing a common neurobiological mechanism.
The dysfunction of serotoninergic, noradrenergic and dopaminergic neurotransmission, abnormal
regulation in the hypothalamic–pituitary–adrenal axis (HPA), disturbance of cellular plasticity including
reduced neurogenesis, or chronic inflammation connected with high oxidative damage play a crucial role
in the development of anxiety and depression. The present study was aimed to investigate the effects of
atenolol alone and in combination with alprazolam/escitalopram on anxiety, depression and oxidative
stress. Wistar albino rats were subjected to 21 day treatment of drugs then exposed to elevated-plus
maze (EPM) and modified forced swim test (MFST), and oxidative stress markers were estimated in isolated
brain tissue of all groups. The results indicated that atenolol in combination with alprazolam/escitalopram
exhibited antidepressant effects by significantly decreasing the immobility and increasing the swimming
behavior in the MFST and anti-anxiety effects by increasing the percentage preference and number of
open arm entries as well as time spent in open arm in EPM. Pretreatment with atenolol alone and combination
with alprazolam/escitalopram also ameliorated tissue glutathione (GSH) and decreased malondialdehyde
(MDA) level significantly which explore antioxidant properties of drugs, and combination augments the
therapeutic response of monotherapy in depression. In conclusion behavioral and biological findings indicate
that the combination of atenolol with alprazolam/escitalopram has the potential of being highly efficacious in
treating anxiety and depressive disorders as well as oxidative stress

Evidence shows that inflammatory and immune processes within the brain might account for the path... more Evidence shows that inflammatory and immune processes within the brain might account for the pathophysiology
of epilepsy. Therefore, developing new antiepileptic drugs that can modulate seizures
through mechanisms other than traditional drugs is required for the treatment of refractory epilepsy.
This study aims to determine the relationship between brain inflammation and epilepsy, to examine the
contribution of some biochemical parameters involved in brain inflammation, and to address the effect of
pharmacological interventions using some anti-inflammatory and immunomodulatory drugs in an experimental
epilepsy model. Adult male rats were divided into seven groups of 20. G1 was the normal,
non-treated control. G2 was the epileptic, non-treated group. G3–G7 were treated with celecoxib,
methotrexate, azathioprine, dexamethasone, and valproate, respectively, for a period of three weeks.
Induction of status epilepticus (SE) by Li-pilocarpine was performed on groups G2–G7. EEG tracing was
conducted, and inflammatory mediators (brain and serum IL-1ß, IL 6, PGE2, HSP70, TGF-β2, and IFNγ)
were measured. The induction of SE increased the amplitude and frequency of EEG tracing and in-
flammatory mediators more than in the normal control group. Treatments of epileptic rats reduced the
frequency and amplitude of EEG tracing and significantly decreased the levels of inflammatory mediators
in some treated rats compared to G2. These findings demonstrate that some anti-inflammatory and
immunomodulatory drugs can lower the frequency and amplitude of seizures and reduce some in-
flammatory mediators in epilepsy treatments, strengthening the possibility that targeting these immunological
and inflammatory pathways may represent another effective therapeutic approach to preventing
epileptic seizures.

Objective: To determine the drug utilization patterns and outcomes of treatment in terms of metab... more Objective: To determine the drug utilization patterns and outcomes of treatment in terms of metabolic control in the type 2 diabetic patients on oral hypoglycemic agents in the outpatient department in the teaching hospital of Hamdard University, New Delhi, India.
Methods: Patients with established type 2 diabetes (n=184) visiting the outpatient department were interviewed using a structured questionnaire over a period of five months.
Results: Majority of the type 2 diabetic patients in this setting were treated with a multiple oral hypoglycemic agents. The most commonly prescribed oral hypoglycemic agent was biguanides (metformin) followed by sulfonylureas (glimepiride), thiazolidinediones pioglitazone), alphaglucosidase inhibitors (miglitol) and dipeptidyl peptidase-4 inhibitors (vildagliptin). As monotherapy metformin was the most common choice followed by glimepiride and voglibose, the most prevalent multiple therapy was a three-drug combination of glimepiride + metformin + pioglitazone. The study showed poor compliance to the prescribed therapy.
Conclusions: This study prospected the need of patient education and counselled to enhance the patient compliance for prescribed oral hypoglycemic agents and concomitant drugs. There is need for diet control as well as blood glucose and HbA1c monitoring. Metabolic control was found to be poor in the study population. HbA1c monitoring was underutilized. Clinical monitoring of patient’s adherence to the prescribed treatment to achieve good glycemic control is recommended. Measures should be taken to improve patient's adherence to the prescribed treatment.

Male factor infertility, being a complex and heterogeneous disorder, precludes any reliance on a ... more Male factor infertility, being a complex and heterogeneous disorder, precludes any reliance on a single laboratory test and requires broad spectrum assessment. Sociobiological factors also influence the parameters. In this context we examined serum concentrations of nine hormones in infertile and fertile male Makkans. Infertility was implicated in 21% of the population with correlated abnormalities of gonadotrophins, thyroid, thyroid stimulating hormone (TSH), and testosterone. Hypothyroidism was established in 35% and hyperthyroidism in 14% of the infertile population, where 28% of thyroid abnormality constituted an independent infertile group. Hyperprolactinaemia associated with low levels of luteinizing hormone (LH) and testosterone signifies a cluster of 28%, while 14% of testosterone deficiency alone was causal for infertility. However, infertility in 9% of the patients examined might have been psychogenic in nature. We present a responder panel based on cluster analysis.

BACKGROUND: There is now good evidence to suggest that cytochrome P450 (CYP450) may act as an iro... more BACKGROUND:
There is now good evidence to suggest that cytochrome P450 (CYP450) may act as an iron-donating catalyst for the production of hydroxyl ion (OH*), which contributes to proximal tubular cell injury. However, it remains unclear which isoform of CYP450 is involved in this process. Cytochrome P4502E1 (CYP2E1) is a highly labile isoform which is not only involved in free radical generation, but has also been shown to be a source of iron in cisplatin-induced renal injury. This study investigates the role of CYP2E1 in the proximal tubular cell injury induced by hydrogen peroxide (H2O2).
METHODS:
Porcine proximal tubular cells (LLC-PK1) were incubated with H2O2 (1 mM) for 4 h in the presence or absence of 0.1 mM of two CYP2E1 inhibitors; diallyl sulfide (DAS), or disulfiram (DSF), desferrioxamine (DFO) (0.1-0.4 mM), or catalase (CT) (78, 150, 300 U/mL). Cell death was determined by measuring LDH release. CYP2E1 activity was determined by p-nitrophenol hydroxylation after 2 h incubation with H2O2.
RESULTS:
Exposure of LLC-PKI to H2O2 significantly increased cell death. CT, DFO, DAS and DSF significantly reduced H2O2-mediated cell death. Incubation with H2O2 increased CYP2EI activation in time- and dose-dependent manner, which was significantly reduced by CT, DFO, DAS and DSF.
CONCLUSION:
We propose that CYP2E1 activation occurs possibly due to OH* and contributes to H2O2-mediated LLC-PK1 cell necrosis by acting as a source of iron and perpetuating the generation of OH* via the Fenton reaction. Inhibition of CYP2E1 may be a novel approach for the prevention of tubular injury caused by oxidative stress.

Evidence shows that inflammatory and immune processes within the brain might account for the pa-t... more Evidence shows that inflammatory and immune processes within the brain might account for the pa-thophysiology of epilepsy. Therefore, developing new antiepileptic drugs that can modulate seizures through mechanisms other than traditional drugs is required for the treatment of refractory epilepsy. This study aims to determine the relationship between brain inflammation and epilepsy, to examine the contribution of some biochemical parameters involved in brain inflammation, and to address the effect of pharmacological interventions using some anti-inflammatory and immunomodulatory drugs in an experimental epilepsy model. Adult male rats were divided into seven groups of 20. G1 was the normal, non-treated control. G2 was the epileptic, non-treated group. G3–G7 were treated with celecoxib, methotrexate, azathioprine, dexamethasone, and valproate, respectively, for a period of three weeks. Induction of status epilepticus (SE) by Li-pilocarpine was performed on groups G2–G7. EEG tracing was conducted, and inflammatory mediators (brain and serum IL-1ß, IL 6, PGE 2 , HSP70, TGF-β2, and IFNγ) were measured. The induction of SE increased the amplitude and frequency of EEG tracing and in-flammatory mediators more than in the normal control group. Treatments of epileptic rats reduced the frequency and amplitude of EEG tracing and significantly decreased the levels of inflammatory mediators in some treated rats compared to G2. These findings demonstrate that some anti-inflammatory and immunomodulatory drugs can lower the frequency and amplitude of seizures and reduce some in-flammatory mediators in epilepsy treatments, strengthening the possibility that targeting these im-munological and inflammatory pathways may represent another effective therapeutic approach to preventing epileptic seizures.

Occupational exposure to organic solvents was found to be associated with development and progres... more Occupational exposure to organic solvents was found to be associated with development and progression of tubulo-interstitial fibrosis and chronic renal failure. However, the cellular mechanism by which this occurs remains elusive. This study was conducted to evaluate the mode of cell death in proximal tubular cells exposed to organic solvents. LLC-PK1 cell line cytotoxicity due to exposure to 1 mM of either p-xylene or toluene was compared to untreated control by cell viability, LDH release, and DNA fragmentation. Cells were exposed to solvents for 96 hrs. Toluene and p-xylene reduced cell viability and increased DNA fragmentation. LDH release was unchanged. These data indicates that long-term exposure to organic solvents is associated with proximal tubule cell apoptosis, which may be the mechanism of progressive renal fibrosis and renal failure in patients with high solvent exposure.

Monolluma quadrangula (Forssk.) Plowes is used in Saudi traditional medicines to treat gastric ul... more Monolluma quadrangula (Forssk.) Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE) was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg) to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg) orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid–Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the experimental rats pretreated with MHAE compared to the ulcer control group. Immunohistochemistry staining revealed an upregulation of the Hsp70 protein and a downregulation of the Bax protein in rats pretreated with MHAE compared with the control rats. Gastric homogenate showed significantly increased catalase and superoxide dismutase, and the level of malondialdehyde (MDA) was reduced in the rats pretreated with MHAE compared to the control group. In conclusion, MHAE exhibited a gastroprotective effect against ethanol-induced gastric mucosal injury in rats. The mechanism of this gastroprotection included an increase in pH and gastric wall mucus, an increase in endogenous enzymes, and a decrease in the level of MDA. Furthermore, protection was given through the upregulation of Hsp70 and the downregulation of Bax proteins.

Objectives: To study the role of cytochrme P4502E1 (CYP2E1) isoform in hydrogen peroxide H2O2)-in... more Objectives: To study the role of cytochrme P4502E1 (CYP2E1) isoform in hydrogen
peroxide
H2O2)-induced cytotoxicity of LLC-PK1 cells, a proximal tubular cell line.
Methods: LLC-PK1 cells were treated with H2O2 , iron chelator, and CYP2E1
inhibitors. The cytotoxicity was assessed by measuring LDH level. CYP2E1 activity
using the substrate p-nitrophenol.
Results: H2O2 at 1 mM induced LLC-PK1 cytotoxicity (P < 0.001). Addition, of free
iron plus H2O2-caused more toxicity (P < 0.01) as assessed by lactate dehydrogenase
(LDH) release measurement. Moreover free iron induced the CYP2E1 activity was in
a dose-dependent manner. Desferrioxamine as iron chelator inhibited CYP2E1
activation produced by H2O2 (P < 0.01). The cytotoxicity of H2O2 was attenuated by
CYP2E1 inhibitor, DFO, and diallyl sulfide (DAS) (P < 0.001). Taken together, these
data indicate that iron plays a critical role in oxidant induced cytotoxicity to LLCPK1.
Conclusions: Highly liable CYP2E1 may act as an iron donating catalyst for Fenton
reaction production of highly ROS which mediate reperfusion injury. In this regards
cytoprotection against H2O2-induced cellular injury by CYP2E1 inhibition is very
important. This observation may identify new therapeutic targets in the prevention of
ischemia/reperfusion injury in general and in the kidney in particular.

Objectives: The effects of the antihypertensive drug methyldopa on biochemical laboratory finding... more Objectives: The effects of the antihypertensive drug methyldopa on biochemical laboratory findings were monitored both in vitro and in vivo particularly those of metabolites and enzymes which are routinely requested by physicians.
Methods: In vitro and in vivo studies were performed. For the in vitro study, solutions of methyldopa concentrations were prepared according to its maximum serum concentration as reported in the literature and were added to blank, normal serum. The samples then were analysed in parallel with a standard test using the same laboratory techniques. For the in vivo study, blood was collected before starting and two weeks after starting methlydopa therapy from 40 subjects that were newly diagnosed with essential hypertension. The control sera were collected from 30 healthy volunteers of comparable ages. The samples were analysed for glucose, total protein (TP) , urea , creatinine , total cholesterol (TC) , triglyceride (TG) , aspartate transaminase (AST), alanine transaminase (ALT) , lactate dehydrogenase (LDH) and Creatine kinase (CK).
Results: In the in vitro study, methyldopa induced a decrease in the readings of serum glucose, TP, urea, TC, AST, ALT, and CK, whereas the LDH levels recorded an increase. In the in vivo study, methyldopa lead to increases in the levels of serum glucose, TP, urea, TC, TG, AST, ALT and LDH.
Conclusions: Methyldopa induced significant alterations in the in vitro as well as in the in vivo measurements. These alterations are required to be taken seriously by physicians to avoid misinterpretations of data generated during routine practice. All the in vitro changes in biochemical parameters are a result of chemical or physical reactions, whereas the in vivo changes resulted mostly from physiological or metabolic factors.

Background: Diabetes mellitus (DM) is a disorder in which blood sugar levels are abnormally high ... more Background: Diabetes mellitus (DM) is a disorder in which blood sugar levels are abnormally high because either absolute or relative insulin deficiency. Treatment of diabetes involves diet, exercise, education and for most people, drugs. Oral antidiabetic drugs and/or insulin doses may be affected by co-administration of many drugs including aspirin. Dose adjustments may be necessary. The pain killer effect of aspirin is best known for its effects on the two cyclooxygenase enzymes (COX1 & COX2), but, recently, aspirin could specifically inhibit the protein I-kappa-β-kinase beta (IKK-beta). This kinase is used for its role in the cascade of signals that activate the nuclear factor kappa-b (NF-kappa-B) family of cellular genes which regulate inflammatory and immune responses. Now, it turns out that IKK-beta also works in another pathway to contribute to insulin resistance by interfering with insulin signaling. Objective: In view of the recent rodent data demonstrating a potentially important role of IKKβ in mediating insulin resistance and the ability of salicylates to inhibit IKKβ activity, we decided to examine the role of different doses of aspirin (low, moderate and high) in experimentally induced diabetic rats. Materials and Methods: DM in rats were induced by administration of nicoti-namide (NAD), 15 min prior to the single dose of streptozotocin STZ i.p. Ninety male albino rats were used in this study. They were divided into 6 main groups. The first was served as control which receives no medications. The second group was diabetic induced rats as mentioned above. The third group was controlled by insulin after induction of D.M. Groups from the fourth to the six consist of 20 diabetic induced rats and further subdivided into rats taking either aspirin alone in different doses (low, moderate or high) or aspirin and insulin. At the end of the protocol, fasting blood sugar level (FBS), glycosylated hemoglobin (HBA1c%), total serum proteins, C-peptide, lipid profile and C-reactive proteins were measured. Results: Different doses of aspirin showed that moderate and to a greater extent high dose aspirin administration to diabetic rats have greater impact on fasting blood glucose levels whether treated with insulin or not. Again, HBA1c% in diabetic rats treated with insulin and receiving HDA was lower than diabetic rats treated with insulin only or even taking LDA in addition. On the contrary, different doses of aspirin (LDA, MDA&HDA) administration to diabetic rats have no any influence on HBA1c% as compared to normal non-diabetic rats. TGs in diabetic rats receiving MDA alone was elevated as compared to normal non-diabetic rats. Again, moderate and HDA in diabetic rats not taking insulin had high TGs level as compared to diabetic rats treated with insulin only. Conclusion: The study concluded that the inflammatory pathways hold a substantial part in insulin resistance in type 2 DM. The influence of salicylate compounds on insulin sensitivity is multifactorial especially in high doses, and involves both beneficial and deleterious effects depending on the species and experimental model studied.

It has been suggested that exposure to organic solvents may have a role in the impairment of kidn... more It has been suggested that exposure to organic solvents may have a role in the impairment of kidney function that may progress to kidney failure. However, this has never been evaluated with an appropriate analytical study of the kidney functions of those people who are chronically exposed to these chemicals. This study was designed to measure the kidney function of car painters in the city of Makkah, Saudi Arabia. Fifty workers were selected at random for this study and compared to thirty male medical students who were taken as a control group. Blood samples were collected for the analysis of kidney function. The levels of blood urea nitrogen (BUN), creatinine, and uric acid were scientifically higher in the tested group compared to the control group. In addition to this, the levels of these parameters were significantly higher in the serum of car painters who worked in this industry for more than ten years compared to painters who worked for less than ten years. Moreover, the number of car painters who were not using protective gloves and masks during working hours were 43 and the number of car painters who visited specialized clinics because of kidney problems were 45 of the 50 tested volunteers. These findings support the hypothesized association of solvent exposure with the development of chronic renal failure. They should prompt clinicians to give greater attention to patients' occupational exposures. Routine monitoring of kidney functions and the use of protective materials are of greater importance to minimize the occupational diseases caused by organic solvents.

Food poisoning during Hajj season is one of the main hazardous issues where most of the health se... more Food poisoning during Hajj season is one of the main hazardous issues where most of the health services in Saudi Arabia are targeting to minimize every year during Hajj seasons. Ordinarily, food handlers are subjected to medical examination before assignment to work. However, they are mostly lacking proper training in food handling operations, mass feeding, and sanitary practices. This situation may encourage causing food poisoning especially with staphylococcus enterotoxins. 1516 clinical specimens from food handlers of different nationalities in Makkah were microbiologically investigated for bacterial pathogens during the hajj seasons of 2001-2002 in Makkah, Saudi Arabia. 129 Staphylococcus aureus isolates were isolated. Of which, 35% produced enterotoxins A, B, C and D singly or in pairs, when such enterotoxins were evaluated by Reversed Passive Latex Agglutination test (RPLA). Enterotoxins C and A, elaborated by 15.5% and 12.4%, isolates respectively, which showed the highest percentage. They were mostly isolated from nasal swabs than throat swabs. All isolates were resistant to Penicillin G. On the other hand, they were sensitive to Clindamy-cin, Oxacillin and Gentamicin when tested by Kirby-Bauer method. The (RPLA) method yielded satisfactory results.

Zamzam water is well known of its high conductivity. For this fact urologist and nephrologists re... more Zamzam water is well known of its high conductivity. For this fact urologist and nephrologists recommend their patients who are suffering from kidney stones not to drink this water because it could worse their health status. This study was conducted to investigate the effect of Zamzam water on calcium oxalate nephrotoxicity in experimentally induced kidney stones in male Wistar albino rats. Calcium oxalate crystals were induced by orally administration of 200 mg of glycolic acid dissolved in the drinking water. The rats were divided into three groups; six rats each. These include positive control group (given glycolic acid), test group (given glycolic acid plus Zamzam water) and negative group (given drinking water only). After two weeks of treatment, blood analysis of blood urea nitrogen (BUN) and creatinine showed significant differences in positive control group compared to the negative control group, whereas no significant differences were noticed in the level of BUN and creatinine between both the negative control and the test group. Moreover , urine analysis showed a high density of calcium oxalate crystals in the positive control group, whereas no crystals were detected in the negative control and the test groups. Histopa-thological investigations showed damaging in kidneys of the positive control group with no tissue abnormalities in the negative control and the test group. I concluded from this study that Zamzam water prevents the formation calcium oxalate stone, which probably mean that it has no negative effect on patients suffering from kidney disorders due to crystals formation.

The effects of khat on the hormonal levels have been established; however, the effects on human b... more The effects of khat on the hormonal levels have been established; however, the effects on human beings are controversial. The aim of our study was to investigate the possible effects of khat on the levels of serum thyroid hormones, tes-tosterone, estradiol (E2), prolactin and cortisol in men. A total of 50 blood samples were collected from healthy males who referred to chew khat for more than 10 years and analyzed for the above hormones. The results were compared to the hormonal levels of 35 non khat chewers. Chewing khat causes significant increases in the testosterone (P < 0.03), prolactin (P < 0.05), E2 (P < 0.00005), FT3 (P < 0.04), and TSH (P < 0.05) levels. No significant differences were found in the serum level of FT4 between the two groups. The level of cortisol were significantly lower (P < 0.001) in the khat chewers group compared to the control group. This study suggests that khat chewing can cause reduction in the cortisol level, which may cause increases of testosterone, prolactin and E2. In addition, chewing khat increases the level of TSH and FT3 serum levels. Therefore, khat may contribute to the relevant disorders caused by abnormal levels of the studied hormones in the people who are chewing khat

The overuse of clinical laboratory services has been documented for many years. This overuse use ... more The overuse of clinical laboratory services has been documented for many years. This overuse use does not contribute to the quality of medical care, does not shorten hospital stay, nor reduce mortality. The utilization of diagnostic laboratories has increased over the last decade around the world. This increased laboratory use is appropriate if it allows accurate diagnoses to be made, ideal treatment to be identified and monitored, accurate prognoses to be established, and patients' hospital stays to be shortened. Thus, improving the appropriateness of testing behavior and reducing the number of laboratory tests have been recognized as essential parts of quality improvement program. In this study, the effectiveness of a computer-based system in improving the laboratory test-ordering in a general hospital was investigated. The study was conducted through four stages, the preparation stage, the pre-intervention stage, the post-intervention 1) stage and post-intervention 2) stage. Guideline and computer system were developed during preparation stage. Medical records were reviewed against guideline recommendations before any intervention during the pre-intervention stage, after guideline dissemination through educational workshops during the post intervention 1) stage, and after implementation of the computer system with the new requesting form during the post intervention 2) stage. The study revealed that the computer-based system achieved a statistically significant increase in the percentage of appropriate use from 44.6% in the post-intervention 1) stage to 55.6%, and a statistically significant increase in the compliance with guideline by prescriber as well as increased in guideline conformity rate from 16.7% in the post-intervention 1) stage to 32.5% in the post-intervention 2) stage, and decreased in the percentage of prescribers whose level was unsatisfactory from 85.4% the post-intervention 1) stage to 66.7% in the post-intervention 2) stage.

Drug Design, Development and Therapy, 2015

Monolluma quadrangula (Forssk.) Plowes is used in Saudi traditional medicines to treat gastric ul... more Monolluma quadrangula (Forssk.) Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE) was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg) to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg) orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid-Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the experimental rats pretreated with MHAE compared to the ulcer control group. Immunohistochemistry staining revealed an upregulation of the Hsp70 protein and a downregulation of the Bax protein in rats pretreated with MHAE compared with the control rats. Gastric homogenate showed significantly increased catalase and superoxide dismutase, and the level of malondialdehyde (MDA) was reduced in the rats pretreated with MHAE compared to the control group. In conclusion, MHAE exhibited a gastroprotective effect against ethanol-induced gastric mucosal injury in rats. The mechanism of this gastroprotection included an increase in pH and gastric wall mucus, an increase in endogenous enzymes, and a decrease in the level of MDA. Furthermore, protection was given through the upregulation of Hsp70 and the downregulation of Bax proteins.

Toxicology mechanisms and methods, 2008

Successful use of doxorubicin as an antitumor agent is limited by its cardiotoxicity, which takes... more Successful use of doxorubicin as an antitumor agent is limited by its cardiotoxicity, which takes different forms and results from multiple biochemical alterations in the cell. This study addresses the possibility to overcome these adverse effects by studying the effects of N-(2-hydroxypropyl)methacrylamide (HPMA) polymer, which contains doxorubicin attaching to it. Both time-and dose-dependent studies were conducted using DU145 cell lines. The results of this study reveal that doxorubicin attached to HPMA can be used successfully in treating cancer instead of doxorubicin alone, which may open a new gate for clinicians and scientists, leading to overcoming the resistance and side effects of the currently used antitumor agents.

Drug Design, Development and Therapy, 2015

Monolluma quadrangula (Forssk.) Plowes is used in Saudi traditional medicines to treat gastric ul... more Monolluma quadrangula (Forssk.) Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE) was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg) to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg) orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid-Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the experimental rats pretreated with MHAE compared to the ulcer control group. Immunohistochemistry staining revealed an upregulation of the Hsp70 protein and a downregulation of the Bax protein in rats pretreated with MHAE compared with the control rats. Gastric homogenate showed significantly increased catalase and superoxide dismutase, and the level of malondialdehyde (MDA) was reduced in the rats pretreated with MHAE compared to the control group. In conclusion, MHAE exhibited a gastroprotective effect against ethanol-induced gastric mucosal injury in rats. The mechanism of this gastroprotection included an increase in pH and gastric wall mucus, an increase in endogenous enzymes, and a decrease in the level of MDA. Furthermore, protection was given through the upregulation of Hsp70 and the downregulation of Bax proteins.

Toxicology mechanisms and methods, 2008