Increased Oxidative Stress in Rat Liver and Pancreas during Progression of Streptozotocin-Induced Diabetes

Abstract

1. Oxygen free radicals have been suggested to be a contributory factor in complications of diabetes mellitus. There are many reports indicating the changes in parameters of oxidative stress in diabetes mellitus. In this study we aimed to identify whether oxidative stress occurs in the liver and pancreas in the initial stages of development of diabetes. 2. We therefore investigated the lipid peroxide level (thiobarbituric acid-reactive substances, TBARS) and activities of antioxidant enzymes [superoxide dismutase (SOD), catalase and glutathione peroxidase] in liver and pancreas of control and streptozotocin-induced diabetic rats at various stages of development of diabetes. 3. Male Sprague-Dawley rats were divided into two groups: group I, control (n = 42) and group II, diabetic (n = 42). Each group was further subdivided into seven groups consisting of six rats each. Rats in these subgroups were studied at weekly intervals (0 to 6 weeks). Plasma glucose levels, TBARS levels and activities of antioxidant enzymes were measured in liver and pancreas at various time intervals. 4. There was a significant (P < 0.05) and progressive increase in TBARS levels of liver and pancreas in the diabetic group. Total SOD and Cu-Zn-SOD activity increased (P < 0.05) with progression of diabetes while Mn-SOD activity showed no significant change in either tissue. Catalase and glutathione peroxidase activities increased significantly (P < 0.05) in liver and pancreas. 5. Immunohistochemical study of pancreatic islet revealed a decrease in the expression of insulin with progression of diabetes. However, glucagon and somatostatin showed an increase in immunoreactivity and a difference in their distribution pattern. 6. The findings of the present study suggest that oxidative stress starts at early onset of diabetes mellitus and increases progressively. In conclusion, the structural damage to these tissues or complications of diabetes mellitus may be due to oxidative stress.

Regulation of Glutathione S-Transferase Mu with type 1 diabetes and its regulation with antioxidants

“…Lipid peroxidation also cause protein damage and inactivation of membrane bound enzymes either through direct attack by free radicals or through chemical modification by its end products which are MDA and 4-hydroxynonenal (4-HNE) [26]. According to our results, lipid peroxidation levels in the liver tissues of diabetic rats were significantly higher compared to controls and these findings are in agreement with the results of other related studies [23,27,28]. This marked increase in the lipid peroxidation rates in diabetic tissues suggests an accumulation of oxygen free radicals which can be due to either increased production and/or decreased elimination.…”

Anthocephalus cadamba (Roxb.) Miq., Rubiaceae, extract shows hypoglycemic effect and eases oxidative stress in alloxan-induced diabetic rats

“…This could be due to the fact that the brain contains relatively high concentration of easily peroxidizable fatty acids (Carney et al, 1991). In agreement with previous studies (Kakkar et al, 1998), the induction of diabetes in rats with alloxan resulted in an increase in lipid peroxidation (TBARS), an indirect evidence of intensified free radical production. Most of the tissue damage is thought to be free-radicals mediated by attacking membranes through peroxidation of unsaturated fatty acids.…”

Investigation of hypoglycemic, hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark in diabetic rats

“…It is well established that free radicals derived from oxygen have been implicated in the pathophysiology of diabetes mellitus and other diseases [29] . A number of studies revealed that oxidative stress plays a major role in the development, progression of diabetes and its related complications [30][31][32][33][34][35][36][37][38][39] .…”