Atorvastatin treatment reduces exercise capacities in rats: involvement of mitochondrial impairments and oxidative stress

Bouitbir J, Charles AL, Rasseneur L, Dufour S, Piquard F, Geny B, Zoll J. Atorvastatin treatment reduces exercise capacities in rats: involvement of mitochondrial impairments and oxidative stress. J Appl Physiol 111: 1477-1483, 2011. First published August 18, 2011; doi: 10.1152/japplphysiol.00107.2011.-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.