Alteration of antioxidants during the progression of heart disease in streptozotocin-induced diabetic rats

Involvement of oxidative stress is implicated in the progression of complic ation of diabetes mellitus. With respect to heart diseases, we have studied role of oxidative stress/antioxidants using rats treated with streptozotoc in to induce diabetes (DM). Hemodynamic and echocardiographic measurements showed thickening of the wall and an increase in the internal dimension of the left ventricle (LV) in DM rats at 8th week. Decrease in diastolic poste rior wall velocity and rate of LV pressure change, and increase in LV end d iastolic pressures also proved cardiac dysfunction. These changes were furt her developed in DM rats after 12 weeks. Utilizing rat hearts at 8th and 12 th weeks, the following estimations were performed. There was a decrease in the activity of Mn-superoxide dismutase (SOD), suggesting abnormal mitocho ndrial metabolism of reactive oxygen species. The level of glutathione (GSH ) decreased concomitant with a decrease in the expression of gamma -glutamy lcysteine synthetase (gamma -GCS). The expression of transforming growth fa ctor-beta1 (TGF-beta1), known as a growth factor and a suppressor of GSH sy nthesis, elevated in DM rat hearts. Immunohistochemical estimation showed a n increase in type IV collagen in DM hearts. Collectively, it was suggested a linkage between mitochondrial damage to generate reactive oxygen species and inactivation of R ln-SOD and elevation of the expression of TGF-beta1 to lead suppression of GSH synthesis and induction of fibrous change for th e consequent cardiac dysfunction in DM.