Oxidative stress in Cohen diabetic rat model by high-sucrose, low-copper diet: inducing pancreatic damage and diabetes

Increased oxidative stress contributes to the development and progression of both types of diabetes mellitus (DM) and its complications. In the Cohen diabetic (CD) rats, a known genetic model of nutritionally induced type 2 DM, a high-sucrose, low-copper diet (HSD) induces within 4 weeks DM in the sensitive (CDs) rats but not in the resistant (CDr) rats. To assess the possible involvement of oxidative stress in the induction of DM, we studied the effect of HSD on the tissue levels of antioxidants and the extent of oxidative injuries in these animals in comparison with the regular outbred strain of nondiabetic Sabra rats. The specific aims were to investigate, at the onset of HSD-induced DM, (1) the extent of oxidative injury, as reflected by levels of malondialdehyde and protein carbonyl groups; (2) the overall antioxidant capacities to cope with increased oxidative stress; and (3) the modification of oxidative damage biomarkers in various tissues of CDr, CDs, and Sabra rats. Female CDs, CDr, and Sabra rats were fed regular diet or HSD for 4 to 5 weeks; and several parameters of oxidative injuries and antioxidant levels were determined. Changes in the levels of nonenzymatic low-molecular weight antioxidants (LMWAs) were measured by cyclic voltammetry and oxygen radical absorbance capacity. The activities of the antioxidant enzymes superoxide dismutase and catalase were measured. Oxidative damage was evaluated by measuring lipid peroxidation and protein oxidation. (1) In all animals fed HSD, the levels of LMWAs were decreased in most organs, although not plasma. (2) A significant difference was consistently found in antioxidant enzymes' activities in the pancreas of HSD-fed CDs rats, but not in other tissues. (3) The activities of superoxide dismutase and catalase and the levels of malondialdehyde and protein carbonyl group increased, whereas the levels of LMWAs decreased, in the pancreas of HSD-fed CDs rats. In the CD rats that develop DM when fed HSD, the pancreas showed susceptibility to oxidative stress-induced injuries. Thus, enhanced oxidative stress seems to play a role in the pathogenesis of DM in this strain.