Abstract
Statins are widely used besides their myopathic side effects, ranging from mild myalgia to fatal rhabdomyolysis. Resveratrol is one of the most popular over the counter products used for similar purposes with statins. The aim of this study was to elucidate the myopathic effects of atorvastatin and coadministered resveratrol in male rat skeletal muscle via morphological analyses and immunohistochemistry studies. Control group received 1.5 ml of drinking water by oral gavage and 1 ml 15% ethanol (vehicle of resveratrol) i.p. for 14 days daily; atorvastatin group was treated with 40 mg/kg atorvastatin by oral gavage and 1 ml 15% ethanol i.p. for 14 days daily. Resveratrol + atorvastatin group was treated with 40 mg/kg atorvastatin by oral gavage and 20 mg/kg i.p resveratrol for 14 days daily. Atorvastatin treatment resulted with a moderate inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) immunoreactivity in nucleus and strong immunoreactivity in fibers. Control group and resveratrol + atorvastatin group showed weak iNOS and eNOS immunoreactivity in nucleus and moderate immunoreactivity muscular fibers. Treatment with atorvastatin resulted in a significantly shortened fibrils, and resveratrol co-treatment reversed this effect. Resveratrol and atorvastatin co-treatment could be an alternative treatment to prevent the myositis adverse effects of atorvastatin on skeletal muscle. Key words: Atorvastatin, myositis, resveratrol.
Highlights
5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase reaction is the rate limiting step of cholesterol biosynthesis and the primary mechanism of action of HMG-CoA reductase inhibitors is to lower cholesterol levels (Evans and Rees, 2002)
Our results showed that the treatment of rats with atorvastatin have resulted with a significantly shortened muscle fibrils in trapezius, gastrocnemius, semitendinosus and biceps femoris muscles (20.48 ± 0.91, 18.07 ± 1.6, 19.53 ± 1.1, 20.52±1.0 μm, respectively) when compared with control group (34.22 ± 1.07, 32.01 ± 1.52, 33.0 ± 2.10, 31.65 ± 1.0 μm, respectively) (p < 0.05 for trapezius, gastrocnemius, semitendinosus and p < 0.01 for biceps femoris)
Co-treatment with resveratrol prevented the shortening of muscle fibrils caused by statin treatment alone
Summary
5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase reaction is the rate limiting step of cholesterol biosynthesis and the primary mechanism of action of HMG-CoA reductase inhibitors (statins) is to lower cholesterol levels (Evans and Rees, 2002). Statins are widely used in the prevention of cardiovascular events They are generally well tolerated, different grades of myopathy, ranging from mild myalgia to fatal rhabdomyolysis has been reported (Abourjaily et al, 2003; Omar et al, 2002; Graham et al, 2004). The risk of rhabdomyolysis with currently marketed statins is very low, symptomatic muscle weakness and pain are much more frequent Several possible mechanisms such as depletion of secondary metabolic intermediates, induction of apoptosis and alterations of chloride channel conductance within myositis have been proposed for statin-associated myopathy (Pierno et al, 2009). Resveratrol reduces the synthesis of lipids and eicosanoids, which promote inflammation and atherosclerosis (Soner et al, 2010) Such multiple protective effects of resveratrol increase its demand as an OTC product even for statin users. The present study was designed to elucidate the effects of combined treatment of resveratrol on atorvastatin-induced myopathy in male rat skeletal muscle via morphological analyses and immunohistochemistry studies
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