Skeletal muscle ischemia-reperfusion injury and cyclosporine A in the aging rat.
Fiche publication
Date publication
juin 2016
Journal
Fundamental & clinical pharmacology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHAMARAUX-TRAN Thiên-Nga, Pr GENY Bernard
Tous les auteurs :
Pottecher J, Kindo M, Chamaraux-Tran TN, Charles AL, Lejay A, Kemmel V, Vogel T, Chakfe N, Zoll J, Diemunsch P, Geny B
Lien Pubmed
Résumé
Old patients exhibit muscle impairments and increased perioperative risk during vascular surgery procedures. Although aging generally impairs protective mechanisms, data are lacking concerning skeletal muscle in elderly. We tested whether cyclosporine A (CsA), which protects skeletal muscle from ischemia-reperfusion (IR) in young rats, might reduce skeletal muscle mitochondrial dysfunction and oxidative stress in aging rats submitted to hindlimb IR. Wistar rats aged 71-73 weeks were randomized to IR (3 h unilateral tourniquet application and 2 h reperfusion) or IR + CsA (10 mg/kg cyclosporine IV before reperfusion). Maximal oxidative capacity (VM ax ), acceptor control ratio (ACR), and relative contribution of the mitochondrial respiratory chain complexes II, III, IV (VS ucc ), and IV (VTMPD /Asc ), together with calcium retention capacity (CRC) a marker of apoptosis, and tissue reactive oxygen species (ROS) production were determined in gastrocnemius muscles from both hindlimbs. Compared to the nonischemic hindlimb, IR significantly reduced mitochondrial coupling, VMax (from 7.34 ± 1.50 to 2.87 ± 1.22 μMO2 /min/g; P < 0.05; -70%), and VS ucc (from 6.14 ± 1.07 to 3.82 ± 0.83 μMO2 /min/g; P < 0.05; -42%) but not VTMPD /Asc . IR also decreased the CRC from 15.58 ± 3.85 to 6.19 ± 0.86 μMCa(2+) /min/g; P < 0.05; -42%). These alterations were not corrected by CsA (-77%, -49%, and -32% after IR for VM ax, VS ucc , and CRC, respectively). Further, CsA significantly increased ROS production in both hindlimbs (P < 0.05; +73%). In old rats, hindlimb IR impairs skeletal muscle mitochondrial function and increases oxidative stress. Cyclosporine A did not show protective effects.
Mots clés
Aging, drug effects, Animals, Cyclosporine, adverse effects, Enzyme Inhibitors, adverse effects, Male, Muscle, Skeletal, drug effects, Random Allocation, Rats, Rats, Wistar, Reactive Oxygen Species, metabolism, Reperfusion Injury, chemically induced
Référence
Fundam Clin Pharmacol. 2016 Jun;30(3):216-25