title: Liver mitochondrial respiratory function and coenzyme Q content in rats on a hypercholesterolemic diet treated with atorvastatin.
abstract: Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are effective drugs in the treatment of hypercholesterolemia, however, their undesirable actions are not fully known. We investigated the effects of atorvastatin on the oxidative phosphorylation and membrane fluidity in liver mitochondria, and also on the coenzyme Q (CoQ) content in the mitochondria, liver tissue, and plasma of rats on a standard (C) and hypercholesterolemic (HCh) diet. Atorvastatin was administered at either low (10 mg kg(-1)) or high dose (80 mg kg(-1)) for four weeks. The high dose of the drug decreased the concentrations of total cholesterol and triacylglycerols in the plasma and liver of rats on a HCh diet. Administration of atorvastatin was associated with decreased oxygen uptake (state 3), and oxidative phosphorylation rate in the mitochondria of both C and HCh rats. Further, the drug influenced mitochondrial membrane fluidity and dose-dependently reduced concentrations of oxidized and reduced forms of CoQ in the mitochondria. Our findings point to an association between in vivo administration of atorvastatin and impaired bioenergetics  in the liver mitochondria of rats, regardless of diet, in conjunction with simultaneous depletion of oxidized and reduced CoQ forms from the mitochondria. This fact may play a significant role in the development of statin-induced hepatopathy.
authors.affiliation: Pharmacobiochemical Laboratory of Third Department of Internal Medicine, Comenius University, Bratislava, Slovak Republic. olga.ulicna@fmed.uniba.sk
authors.forename: O
authors.initials: O
authors.lastname: Uličná
authors.forename: O
authors.initials: O
authors.lastname: Vančová
authors.forename: I
authors.initials: I
authors.lastname: Waczulíková
authors.forename: P
authors.initials: P
authors.lastname: Božek
authors.forename: L
authors.initials: L
authors.lastname: Šikurová
authors.forename: V
authors.initials: V
authors.lastname: Bada
authors.forename: J
authors.initials: J
authors.lastname: Kucharská
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D002784:Cholesterol / Q000494:pharmacology*; D004032:Diet; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D018977:Micronutrients / Q000378:metabolism* / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000378:metabolism*; D011758:Pyrroles / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D014451:Ubiquinone / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018977:Micronutrients; D011758:Pyrroles; D014451:Ubiquinone; D002784:Cholesterol; D000069059:Atorvastatin