title: Atorvastatin treatment reduces exercise capacities in rats: involvement of mitochondrial impairments and oxidative stress.
abstract: Physical exercise exacerbates the cytotoxic effects of statins in skeletal muscle. Mitochondrial impairments may play an important role in the development of muscular symptoms following statin treatment. Our objective was to characterize mitochondrial function and reactive oxygen species (ROS) production in skeletal muscle after exhaustive exercise in atorvastatin-treated rats. The animals were divided into four groups: resting control (CONT; n = 8) and exercise rats (CONT+EXE; n = 8) as well as resting (ATO; n = 10) and exercise (ATO+EXE; n = 8) rats that were treated with atorvastatin (10 mg·kg(-1)·day(-1) for 2 wk). Exhaustive exercise showed that the distance that was covered by treated animals was reduced (P < 0.05). Using dihydroethidium staining, we showed that the ROS level was increased by 60% in the plantaris muscle of ATO compared with CONT rats and was highly increased in ATO+EXE (226%) compared with that in CONT+EXE rats. The maximal mitochondrial respiration (V(max)) was decreased in ATO rats compared with that in CONT rats (P < 0.01). In CONT+EXE rats, V(max) significantly increased compared with those in CONT rats (P < 0.05). V(max) was significantly lower in ATO+EXE rats (-39%) compared with that in CONT+EXE rats (P < 0.001). The distance that was covered by rats significantly correlated with V(max) (r = 0.62, P < 0.01). The glycogen content was decreased in ATO, CONT+EXE, and ATO+EXE rats compared with that in CONT rats (P < 0.05). GLUT-4 mRNA expression was higher after exhaustive exercise in CONT+EXE rats compared with the other groups (P < 0.05). Our results show that exhaustive exercise exacerbated metabolic perturbations and ROS production in skeletal muscle, which may reduce the exercise capacity and promote the muscular symptoms in sedentary atorvastatin-treated animals.
authors.affiliation: Université de Strasbourg, EA3072, Faculté de Médecine & Faculté des Sciences du Sport, Strasbourg, France.
authors.forename: Jamal
authors.initials: J
authors.lastname: Bouitbir
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Charles
authors.forename: Laurence
authors.initials: L
authors.lastname: Rasseneur
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dufour
authors.forename: François
authors.initials: F
authors.lastname: Piquard
authors.forename: Bernard
authors.initials: B
authors.lastname: Geny
authors.forename: Joffrey
authors.initials: J
authors.lastname: Zoll
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D019069:Cell Respiration / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D051275:Glucose Transporter Type 4; D006538:Heptanoic Acids; D011758:Pyrroles; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C495694:Slc2a4 protein, rat; D006003:Glycogen; D002784:Cholesterol; D000069059:Atorvastatin; D003402:Creatine Kinase