GW24-e1806 Atorvastatin attenuates oxygen-glucose deprivation/recovery-induced mitochondrial dysfunction in neonatal rat cardiac myocytes

Objectives Atorvastatin (Ator) has been shown to exert protective properties on cardiovascular systems in vivo. However, its mechanism of action remains elusive. Our study aims to assess the potential of Ator to protect the cardiomyocytes exposed to ischaemia-like conditions of oxygen-glucose deprivation/recovery (OGD/R) in vitro and to determine mitochondrial function upon Ator exposure. Methods Primary cardiomyocytes were isolated from neonatal Sprague-Dawley rats. To establish an in vitro model of OGD/R, which resembles ischaemia/reperfusion in vivo, primary cardiomyocytes were exposed to OGD for 10 h followed by a 3 h recovery. Myocardial cell viability was evaluated using the MTT and lactate dehydrogenase (LDH) release assays. The opening of the mitochondrial permeability transition pore (mPTP), Ca2+concentration and mitochondrial membrane potential (ΔΨm) in cardiomyocytes were measured using confocal laser scanning microscopy (CLSM). Reactive oxygen species (ROS) generation was examined using flow cytometry. Results Ator (1 μM) markedly attenuated OGD/R-induced cell injury and maintained the functional integrity of mitochondria by alleviating calcium overload and ROS burst, inhibiting the opening of mPTP and preventing ΔΨm depolarisation (P < 0.05 vs. OGD/R group). However, these effects of Ator were blocked by administration of the mPTP opener lonidamine (LND, 30 μM) and the mitochondrial ATP-sensitive potassium channel (mitoKATP channel) blocker 5-hydroxydecanoic acid (5-HD, 100 μM). Conclusions Ator has tremendous pharmacological potential in protecting against OGD/R-induced cell injury by preserving the functional integrity of mitochondria.