Abstract
Apoptosis is upregulated in all forms of diabetes, and the mitochondria act as target in diabetes pathophysiology. Quercetin and vitamin E have both 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 cardiomyocytic death via regulation of the mitochondria permeability transition (mPT) pore opening. 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 and caspase 3 and 9 were determined by immunohistochemistry, while lesions assessed by histology. Diabetic heart mPT pore showed larger amplitude swelling than control, while mLPO levels were 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 hemorrhagic lesions in diabetic rat hearts. Quercetin and vitamin E treatment reversed these effects, suggestive of their anti-apoptotic effect. Quercetin and vitamin E protection in diabetes is mediated by mPT pore inhibition and modulation of mitochondrial-mediated apoptosis.
Highlights
Diabetes mellitus (DM) is an epidemic that has affected approximately 382 million people worldwide and expected to increase to about 592 million of the world population in 2035, generating a major world public health burden [1]. 2017)
Diabetic heart mitochondria permeability transition (mPT) pore showed larger amplitude swelling than control, while mitochondrial lipid peroxidation (mLPO) levels was increased in diabetic rats relative to control, this resulted in cytochrome c release
Quercetin and vitamin E protection in diabetes is mediated by mPT pore inhibition and modulation of mitochondrial-mediated apoptosis
Summary
Diabetes mellitus (DM) is an epidemic that has affected approximately 382 million people worldwide and expected to increase to about 592 million of the world population in 2035, generating a major world public health burden [1]. 2017). The occurrence of diabetes mellitus is affecting a number of organs including the kidney, eyes, and heart [2,3,4]. Diabetes is a major risk factor in the development of various cardiovascular diseases including heart failure. It has been shown that hyperglycemia associated with this pathological condition causes severe oxidative stress to the cardio-myocytes and leads to diabetic cardiomyopathy [5]. Cardiovascular disease occurrence in diabetes is significantly high, with studies showing an increased risk of heart failure due to inadequate hyperglycemia control [7]. Quercetin and vitamin E have shown usefulness in the delay of progression of diabetes-induced complications. 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
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