Resveratrol for protection against statin toxicity in C2C12 and H9c2 cells

J Biochem Mol Toxicol. 2020 Jun;34(6):e22484. doi: 10.1002/jbt.22484. Epub 2020 Mar 20.

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.

Keywords: cytotoxicity; lipid-lowering drug; metabolic inhibition; nutritional supplement.

MeSH terms

  • Animals
  • Atorvastatin / adverse effects
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Line
  • Cell Survival / drug effects*
  • Fluvastatin / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Lovastatin / adverse effects
  • Mice
  • Myoblasts / drug effects*
  • Myoblasts / metabolism
  • Pravastatin / adverse effects
  • Protective Agents / pharmacology*
  • Rats
  • Resveratrol / pharmacology*
  • Signal Transduction / drug effects
  • Simvastatin / adverse effects

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Protective Agents
  • Fluvastatin
  • Lovastatin
  • Atorvastatin
  • Simvastatin
  • Casp3 protein, rat
  • Caspase 3
  • Caspase 7
  • Casp7 protein, rat
  • Pravastatin
  • Resveratrol