Some Agents Modulating Experimental Streptozotocin-Induced Diabetes Mellitus In Rats

Abstract

Autoimmune destruction of pancreatic B-cells during the development of type I diabetes rs a complex process involving both cellular and humoral elements of cytotoxicity. Activated T-cells and macrophages secrete many inflammatory cytokines that produce their ­ cells toxic effect through generation of oxygen free radicals. Increased oxygen free radical production is associated with impaired insulin secretion as P-cells are more susceptible to the effect of free radicals than other tissues. Lipid peroxidation is a chain reaction that is capable to produce widespread tissue damage. It would result in damage to the membrane structures and would function in vivo and in vitro. An association between increased I ipid peroxidation and the diabetogenic process in type I diabetes has been proposed in many studies.

In our study, performed on streptozotocin-induced diabetes in rats as a model of type I diabetes, preventive dose of vitamin E 200mg/kg/day orally for 3 weeks significantly prevented the rise in blood glucose level without complete protection against development of type I diabetes. Also, vitamin E prevented the rise in the level of pancreatic tissue malondialdehyde denoting complete protection against lipid peroxidation. Streptozotocin produced mild destructive changes in the pancreatic beta­ cells following vitamin E administration.

As regard L-arginine (NO donor), 300mg/kg/day orally for 3 weeks, preventive dose was not protective against type I diabetes as evident by non significant changes in the levels of blood glucose and pancreatic tissue malondialdehyde inspite of moderate pancreatic beta­ cell destruction.