Atorvastatin treatment reduces exercise capacities in rats and exacerbates metabolic perturbations and oxidative stress in skeletal muscle. - GreenMedInfo Summary
Atorvastatin treatment reduces exercise capacities in rats: Involvement of mitochondrial impairments and oxidative stress.
J Appl Physiol. 2011 Aug 18. Epub 2011 Aug 18. PMID: 21852406
1Hopitaux Universitaires.
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/day for two weeks). 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 to CONT rats and was highly increased in ATO+EXE (+226 %) compared to that in CONT+EXE rats. The maximal mitochondrial respiration (V(max)) was decreased in ATO rats compared to that in CONT rats (P<0.01). In CONT+EXE rats, V(max) significantly increased compared to those in CONT rats (P<0.05). V(max) was significantly lower in ATO+EXE rats (-39 %) compared to 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 to that in CONT rats (P<0.05). GLUT-4 mRNA expression was higher after exhaustive exercise in CONT+EXE rats compared to 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.