Resveratrol for protection against statin toxicity in C2C12 and H9c2 cells

Abstract

Statins are among the most commonly prescribed drugs for the treatment of high blood cholesterol. Myotoxicity of statins in certain individuals is often a severe side effect leading to withdrawal. Using C2C12 and H9c2 cells, both exhibiting characteristics of skeletal muscle cells, we addressed whether resveratrol (RSV) can prevent statin toxicity. Statins decreased cell viability in a dose and time‐dependent manner. Among the five statins tested, atorvastatin, simvastatin, lovastatin, pravastatin, and fluvastatin, simvastatin is the most toxic one. Simvastatin at 10 µM caused about 65% loss of metabolic activity as measured by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays in C2C12 cells or H9c2 cells. Inhibition of metabolic activity correlates with an increase in caspase activity. RSV was found to protect H9c2 cells from simvastatin‐induced activation of caspase‐3/7. However, such protection was not found in C2C12 cells. This cell type‐dependent effect of RSV adds to the complexity in muscle cell toxicity of statins.

Simvastatin Inhibits NLRP3 Inflammasome Activation and Ameliorates Lung Injury in Hyperoxia-Induced Bronchopulmonary Dysplasia via the KLF2-Mediated Mechanism

“…For most people, statins are safe and well tolerated. However, 30% of statins have been associated with intolerance, including the most prevalent muscle and liver toxicities [ 57 ]. The strengthening of childhood hypercholesterolemia screening has increased the use of statins in children [ 58 ].…”

Pleiotropic use of Statins as non-lipid-lowering drugs

“…Statins can cause many side effects while treating various diseases. The side effects of statins include liver toxicity [65], muscle toxicity [66] and neurotoxicity [67], as well as the following: effects on coenzyme Q10 and the mitochondrial membrane [68,69]; effects on isopentenyl and glycosylase, and effects on ion channel signaling [70]. The dysfunction of cellular metabolism further leads to various adverse effects.…”