Coenzyme Q10 protects against statin-induced myotoxicity in zebrafish larvae ( Danio rerio )

Abstract

3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the rate-limiting enzyme of the mevalonic acid pathway and is required for cholesterol biosynthesis and the synthesis of Coenzyme Q10 (CoQ10). Statins inhibit HMGCR, thus inhibiting the downstream products of this pathway including the biosynthesis of decaprenyl-pyrophosphate that is critical for the synthesis of Coenzyme Q10 (CoQ10). We show that zebrafish (Danio rerio) larvae treated in tank water with Atorvastatin (ATV; Lipitor) exhibited movement alterations and reduced whole body tissue metabolism. The ATV-inhibition of HMGCR function altered transcript abundance of muscle atrophy markers (atrogen-1, murf) and the mitochondrial biogenesis marker (pgc-1α). Furthermore, ATV-induced reduction in larval response to tactile stimuli was reversed with treatment of CoQ10. Together, the implication of our results contributes to the understanding of the mechanisms of action of the statin-induced damage in this model fish species.