RESUMO
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