Captopril and / or melatonin attenuates diabetes induced metabolic disorders and oxidative stress in rats

There is a clear link between diabetes, metabolic disorders and oxidative stress. Hyperglycemia leads to hyperlipidemia, renal dysfunction, free radical generation and alteration of endogenous antioxidants. The present study is an attempt to evaluate the possible protective effect of captopril [CAP] and/or melatonin [MLT] against Streptozotocin [STZ]-induced metabolic disorders, renal dysfunction and oxidative stress in rats. STZ challenge induced diabetic model that was characterized biochemically and histologically. Serum glucose, lipid profile, creatinine, urea, pancreatic tissue contents of glutathione [GSH] and malondialdehyde [MDA] as well as pancreatic catalase [CAT] and superoxide dismutase [SOD] activities were determined. CAP and/or MLT were given in a dose of [10 mg/ kg/day p.o.] for 10 consecutive days prior to STZ [60 mg/ kg as a single dose] treatment followed by 30 consecutive days in previous dose regimen. Results revealed that STZ induced a marked increase in serum glucose, serum triglycerides [TG], total cholesterol [TC] and LDL-cholesterol as well as serum creatinine and urea. On the contrary HDL-cholesterol was markedly decreased in STZ-treated group. Moreover, STZ induced significant decrease in the pancreatic content of GSH and SOD with concomitant increase in MDA content. Administration of CAP or [CAP plus MLT] prior to STZ treatment revealed a marked decrease in serum glucose, TC, TG and LDL as compared to STZ-treated group. Furthermore, treatment with CAP and MLT decreased the elevated serum levels of creatinine and urea. On opposite direction, CAP, MLT and their combinations were significantly increased pancreatic GSH content and SOD activity while decreases pancreatic MDA content when compared to STZ- alone. The biochemical observations were further confirmed histologically. STZ induced degenerative, necrotic changes in the islets of langerhans of pancreas and leukocytic infiltration. Pancreatic degenerative changes were improved by treatment with CAP and MLT. These results confirm that administration of CAP and/or MLT decrease STZ-induced metabolic disorders probably via regulation of oxidant / anti-oxidant balance and by modulation of hyperlipidemia associated with STZ-induced diabetes in rats. CAP, MLT and their combinations presumably due to their antioxidant, free radicals scavenging activity and hypolipidemic effects is highly protective against the biochemical and histopathological changes associated with STZ-induced diabetes

Neuroprotective effect of melatonin against ethanol-induced damage in rat brain stem

Chronic ethanol administration has been found to have neuronal damaging effect through free radical generation. The aim of this study is to determine the possible neuroprotective effect of melatonin [MLT] against ethanol induced neuronal damage in the brain stem of male albino rats. Rats were randomly divided into 3 groups: control group, 35% ethanol-treated group and melatonin [l0mg/kg I. P. for 7 consecutive days] pre-treated ethanol group. Administration of ethanol [35%] orally in drinking water for 30 consecutive days decreased glutathione [GSH], dopamine [DA], norepinephrine [NE] and serotonin [5-HT] contents and superoxide dismutase [SOD] activity. The maximal percentage of decrease was 44%, 34%, 41%, 29% and 40%, respectively. On the other hand; there was a progressive increase in malondialdehyde [MDA] level and DNA fragmentation by 128% and 53%, respectively. Melatonin administration prior to ethanol significantly increased. GSH, DA, 5-HT, and NE contents in brain stem by 53%, 30%, 33%, 33% respectively and SOD activity by 35%. MDA level and DNA fragmentation were markedly reduced by 36% and 30%, respectively. Our data suggest that melatonin is capable of at least partially preventing ethanol -induced neurodegeneration in the brain stem of rats. This effect might be attributed to direct free radical scavenging properties and regulation of antioxidative enzyme activity of melatonin