Abstract
Simvastatin is a lipid-lowering agent used to treat hypercholesterolemia and to reduce the risk of heart disease. This study scrutinized the beneficial effects of simvastatin on experimental diabetic cardiomyopathy (DCM), pointing to the role of hyperglycemia-induced oxidative stress and inflammation. Diabetes was induced by intraperitoneal injection of streptozotocin and both control and diabetic rats received simvastatin for 90 days. Diabetic rats showed significant cardiac hypertrophy, body weight loss, hyperglycemia, and hyperlipidemia. Serum creatine kinase MB (CK-MB) and troponin I showed a significant increase in diabetic rats. Simvastatin significantly improved body weight, attenuated hyperglycemia and hyperlipidemia, and ameliorated CK-MB and troponin I. Simvastatin prevented histological alterations and deposition of collagen in the heart of diabetic animals. Lipid peroxidation and nitric oxide were increased in the heart of diabetic rats whereas antioxidant defenses were decreased. These alterations were significantly reversed by simvastatin. In addition, simvastatin decreased serum inflammatory mediators and expression of NF-κB in the diabetic heart. Cardiac caspase-3 was increased in the diabetic heart and decreased following treatment with simvastatin. In conclusion, our results suggest that simvastatin alleviates DCM by attenuating hyperglycemia/hyperlipidemia-induced oxidative stress, inflammation, and apoptosis.
Highlights
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the world
Heart weight/body weight ratio (HW/BW) was significantly (P < 0 01) increased in diabetic rats when compared with the control group; an effect that was significantly (P < 0 05) repressed by simvastatin (Figure 1(b))
Cardiomyopathy is an independent complication of Diabetes mellitus (DM) which occurs in the absence of other heart diseases [29]
Summary
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the world. Diabetes mellitus (DM) is a major contributing factor to CVD and heart failure [1]. A causative relationship between myocardial abnormalities and diabetes has been well demonstrated [2]. Diabetic cardiomyopathy (DCM) is the clinical condition associated with cardiac abnormalities provoked by diabetes [2]. It has been estimated that DCM affects approximately 12% of the diabetic patients and may lead to heart failure and death [3]. Oxidative stress, inflammation, apoptosis, and myocardial interstitial fibrosis are the major features of DCM [4]
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