Coenzyme Q10 or Creatine Counteract Pravastatin-Induced Liver Redox Changes in Hypercholesterolemic Mice

Frontiers in Pharmacology
Ana C MarquesAnibal E Vercesi

Abstract

Statins are the preferred therapy to treat hypercholesterolemia. Their main action consists of inhibiting the cholesterol biosynthesis pathway. Previous studies report mitochondrial oxidative stress and membrane permeability transition (MPT) of several experimental models submitted to diverse statins treatments. The aim of the present study was to investigate whether chronic treatment with the hydrophilic pravastatin induces hepatotoxicity in LDL receptor knockout mice (LDLr-/-), a model for human familial hypercholesterolemia. We evaluated respiration and reactive oxygen production rates, cyclosporine-A sensitive mitochondrial calcium release, antioxidant enzyme activities in liver mitochondria or homogenates obtained from LDLr-/- mice treated with pravastatin for 3 months. We observed that pravastatin induced higher H2O2 production rate (40%), decreased activity of aconitase (28%), a superoxide-sensitive Krebs cycle enzyme, and increased susceptibility to Ca2+-induced MPT (32%) in liver mitochondria. Among several antioxidant enzymes, only glucose-6-phosphate dehydrogenase (G6PD) activity was increased (44%) in the liver of treated mice. Reduced glutathione content and reduced to oxidized glutathione ratio were increased in l...Continue Reading

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Citations

Jan 18, 2019·Circulation Research·Natalie C WardRobert H Eckel
Oct 18, 2019·Cell Stress & Chaperones·Daniela Sayuri MizobutiElaine Minatel
Jul 17, 2020·Expert Opinion on Drug Safety·Rubina MulchandaniAshish Kumar Kakkar
Aug 29, 2019·Journal of Translational Medicine·Estela Lorza-GilHelena C F Oliveira
Dec 12, 2018·Journal of Cellular Physiology·Estela Lorza-GilHelena C F Oliveira
Jul 20, 2019·Antioxidants·Chiara SironiCristina Porta

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Methods Mentioned

BETA
biopsies
Assay

Software Mentioned

MetaboAnalyst

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