Basic Informations

C.V

Mustafa Ahmed Abdel-Reheim

Master Title

Pharmacological Study of The Possible Interactions Between Antidiabetic Drugs and Some Angiotensin Inhibitors in Streptozotocin-Induced Diabetic Rats

Master Abstract

SUMMARY AND CONCLUSIONS In the present study, both in vivo and in vitro experiments were carried out in order to study the possible interactions between certain antidiabetics and selected angiotensin inhibitors in experimental animals. The purpose of the in vitro experiments was to study the possible effects of gliclazide (20, 40 µmol/l), chromium picolinate (20, 40 µmol/l) , captopril (50, 100 µmol/l) and losartan (50, 100 µmol/l), alone and in combination on basal (glucose 3 mmol/l) and glucose 16.7 mmol/l-stimulated insulin secretion using isolated rat pancreatic islets technique. The purpose of the in vivo experiments was to study the possible effects of gliclazide (10 mg/kg), chromium picolinate (1mg/kg), captopril (10 mg/kg) and losartan (5 mg/kg) alone and in combination in streptozotocin (50 mg/kg) - induced diabetic rats. The effects of these treatments on serum glucose, insulin levels, insulin resistance levels & ß-cell function were investigated after two weeks of daily dose administration. The effects of the aforementioned treatments on liver glycogen content and blood GSH, MDA, SOD and nitric oxide were also studied. The main findings of the present study can be summarized as follows: In vitro study: 1. Glucose (16.7 mmol/l) significantly increased insulin secretion from isolated pancreatic islets. 2. Gliclazide (20, 40 µmol/l), captopril (50, 100 µmol/l) and losartan (50, 100 µmol/l) increased both basal and stimulated-insulin secretion from isolated pancreatic islets. 3. Chromium picolinate (20, 40 µmol/l) did not significantly affect both basal and stimulated–insulin secretion from isolated pancreatic islets. 4. Combination of gliclazide (20, 40 µmol/l) and captopril (50, 100 µmol/l) significantly raised basal and stimulated-insulin secretion and this effect was significant from gliclazide alone. 5. Combination of gliclazide (20, 40 µmol/l) and losartan (50, 100 µmol/l) significantly raised basal and stimulated-insulin secretion and this effect was significant from gliclazide alone. 6. Combination of chromium picolinate (20, 40 µmol/l) and captopril (50, 100 µmol/l) significantly raised both basal and stimulated– insulin secretion from isolated pancreatic islets and this effect was not significant from captopril alone. 7. Combination of chromium picolinate (20, 40 µmol/l) and losartan (50, 100 µmol/l) significantly raised both basal and stimulated– insulin secretion from isolated pancreatic islets and this effect was not significant from losartan alone. In vivo study: The following results were obtained: * Effect of streptozotocin on the measured parameters: • STZ increased serum glucose level, decreased serum insulin level, increased insulin resistance level and decreased ß-cell function. • STZ decreased liver glycogen content, increased serum MDA level and decreased blood GSH level, blood SOD level and serum nitric oxide level. * Effect of gliclazide on the measured parameters: • Gliclazide decreased serum glucose level and increased serum insulin level in STZ–induced diabetic rats. In addition it decreased insulin resistance level and increased ß-cell function. • Administration of gliclazide normalized the decrease in liver glycogen content caused by STZ-diabetic rats. Gliclazide also corrected the decrease in blood GSH level, the increase in serum MDA level, the decrease in blood SOD level and the decrease in serum nitric oxide level * Effect of chromium picolinate on the measured parameters: • Chromium picolinate decreased serum glucose level and not affected serum insulin level in STZ–induced diabetic rats. In addition it decreased insulin resistance level and not affected ß-cell function. • Administration of chromium picolinate nearly normalized the decrease in liver glycogen content caused by STZ-diabetic rats. Chromium picolinate. Also corrected the decrease in blood GSH level, the increase in serum MDA level, the decrease in blood SOD level and the decrease in serum nitric oxide level. * Effect of captopril on the measured parameters: • Captopril decreased serum glucose level and not affected serum insulin level in STZ–induced diabetic rats. In addition it decreased insulin resistance level and not affected ß-cell function. • Administration of captopril nearly normalized the decrease in liver glycogen content caused by STZ-diabetic rats. Captopril also corrected the decrease in blood GSH level, the increase in serum MDA level, the decrease in blood SOD level and the decrease in serum nitric oxide level. * Effect of losartan on the measured parameters: • Losartan decreased serum glucose level and not affected serum insulin level in STZ–induced diabetic rats. In addition it decreased insulin resistance level and not affected ß-cell function. • Administration of losartan did not significantly affect the liver glycogen content in STZ- diabetic rats. Losartan also corrected the decrease in blood GSH level, the increase in serum MDA level and the decrease in serum nitric oxide level.

PHD Title

Pharmacological Study of the Possible Protective Effects of Some Antioxidants against Experimentally-Induced Hepatotoxicity in Rats

PHD Abstract

In the present study, the effects of four antioxidants namely saponin, ellagic acid, aesculetin and diosmin on several parameters related to iron-induced hepatotoxicity in rats were studied in comparison with N-acetylcysteine. The antioxidant drugs were given for normal as well as ferrous sulphate-treated rats. Treatments were given to rats as oral daily dose for 10 consecutive days. Hepatic injury was induced by I.P. injection of two doses of ferrous sulphate (30 mg/kg) at 9th and 10th day. The effects of the tested drugs were estimated on serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), serum bilirubin, albumin, total cholesterol (TC) and triglycerides (TG). In liver homogenate, the following parameters were measured; reduced glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) content were measured. Also, histopathological and immunohistochemical studies were carried out for the assessment of tissue eNOS and iNOS.