Quercetin and Vitamin E ameliorate cardio-apoptotic risks in diabetic rats

Abstract Background: Apoptosis is upregulated in all forms of diabetes, with the mitochondria acting as a target in diabetes pathophysiology. Quercetin and vitamin E have shown usefulness in the delay of progression of diabetes-induced complications. However, their effect on the apoptotic process in diabetes mellitus is unknown. We hypothesize that quercetin treatment in diabetes may decrease the propensity for cardio-myocytic death via regulation of the mitochondria permeability transition (mPT) pore opening. Methods: Hearts from normal and streptozotocin-induced diabetic rats were used for the study. Low-ionic strength heart mitochondria were used for swelling assay, and mitochondrial lipid peroxidation (mLPO) activity was spectrophotometrically assessed. Levels of cytochrome c, caspase 3 and 9 were determined by immunohistochemistry, while lesions assessed by histology.Discussion: Diabetic heart mPT pore showed larger amplitude swelling than control, while mLPO levels was increased in diabetic rats relative to control, this resulted in cytochrome c release. This initiated increased caspase 3 and 9 activity in diabetic rats (p<0.05). Histology showed haemorrphagic lesions in diabetic rat hearts. Quercetin and vitamin E treatment reversed these effects, suggestive of their anti-apoptotic effect. Conclusions: Quercetin and vitamin E protection in diabetes is mediated by mPT pore inhibition and modulation of mitochondrial-mediated apoptosis.