Ischemic preconditioning and N-acetylcysteine in a rat model of skeletal muscle ischemia-reperfusion: does antioxidant therapy have an impact on ischemic preconditioning?

Abstract

Background: This study aims to investigate the effects of ischemic preconditioning (IPC) and N-acetylcysteine (NAC) on ischemia-reperfusion (I/R) injury and the impact of simultaneous NAC administration, a reactive oxygen species (ROS) scavenger, with IPC. Methods: Twenty-eight male Sprague-Dawley t ype r ats (230-255 g) were randomly assigned to either of four groups each containing seven rats, including a control group. Rats in the control group underwent ischemia of the lower limbs through occlusion of infrarenal abdominal aorta for 120 min, followed by reperfusion for 50 minute. In the IPC group, three cycles of 10 min ischemia, followed by 10 min reperfusion was formed preceding I/R. NAC group rats received an intravenous bolus of NAC (20 mg/kg) at the termination of ischemia and a maintenance dose of 20 mg/kg/hr throughout the reperfusion period. In IPC+NAC group, an equal amount of NAC was given over an identical infusion time during IPC. Tissue samples were obtained at the end of reperfusion then rats were sacrificed. Results: Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were measured to be lower in all study groups, compared to the control group. Reduced glutathione (GSH) level was higher in NAC group than the remaining groups. No significant difference in parameters studied between IPC and IPC+NAC group. However, MDA and MPO levels were found to be lower and GSH level was higher in IPC group. Conclusion: In the experimental model of I/R injury, both IPC and NAC attenuated tissue injury in rat skeletal muscle. Simultaneous administration of ROS scavenger NAC with IPC did not completely block the protective effect of IPC, however resulted in a partial reduction. This finding suggested that several mechanisms other than ROS might be involved in the process of skeletal muscle IPC.