Assessment of the Preventive Effect of L-carnitine on Post-statin Muscle Damage in a Zebrafish Model

Cells. 2022 Apr 11;11(8):1297. doi: 10.3390/cells11081297.

Abstract

Statins, such as lovastatin, are lipid-lowering drugs (LLDs) that have been used to treat hypercholesterolaemia, defined as abnormally elevated cholesterol levels in the patient's blood. Although statins are considered relatively safe and well tolerated, recipients may suffer from adverse effects, including post-statin myopathies. Many studies have shown that supplementation with various compounds may be beneficial for the prevention or treatment of side effects in patients undergoing statin therapy. In our study, we investigated whether L-carnitine administered to zebrafish larvae treated with lovastatin alleviates post-statin muscle damage. We found that exposure of zebrafish larvae to lovastatin caused skeletal muscle disruption observed as a reduction of birefringence, changes in muscle ultrastructure, and an increase in atrogin-1. Lovastatin also affected heart performance and swimming behaviour of larvae. Our data indicated that the muscle-protective effect of L-carnitine is partial. Some observed myotoxic effects, such as disruption of skeletal muscle and increase in atrogin-1 expression, heart contraction could be rescued by the addition of L-carnitine. Others, such as slowed heart rate and reduced locomotion, could not be mitigated by L-carnitine supplementation.

Keywords: Danio rerio; L-carnitine; cardiac muscle; lovastatin; myotoxicity; skeletal muscle; statins; zebrafish.

MeSH terms

  • Animals
  • Carnitine / metabolism
  • Carnitine / pharmacology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / pharmacology
  • Larva
  • Lovastatin / pharmacology
  • Muscle, Skeletal
  • Zebrafish / metabolism

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lovastatin
  • Carnitine