Penehyclidine hydrochloride ameliorates renal ischemia-reperfusion injury in rats

Background: Renal ischemiaereperfusion (I/R) injury is a major cause of acute kidney failure by mechanisms that involve oxidative stress, inflammation, and apoptosis. Penehyclidine hydrochloride (PHC), a selective anticholinergic agent, possesses anti-inflammatory, anti-oxidative stress, and antiapoptotic effects. Therefore, we investigated the ability of PHC to ameliorate renal I/R injury in Sprague-Dawley rats. Materials and methods: Rats were randomly assigned to three groups (35 rats per group): sham operated, saline-treated I/R, and PHC-treated I/R. After removing the right kidney, renal I/R injury was induced by clamping the left renal artery for 45 min followed by reperfusion. The rats were administered PHC (0.45 mg/kg, intravenously) or saline 30 min before renal ischemia. The blood and kidneys were harvested at 1, 3, 6, 12, or 24 h after reperfusion. Renal function and histologic changes were assessed. Markers of oxidative stress, inflammation, and apoptosis in the kidneys were also measured. Results: PHC treatment significantly attenuated renal dysfunction and histologic damage caused by I/R injury. The treatment also decreased malondialdehyde level and attenuated the reduction in superoxide dismutase activity in the kidney. Moreover, the levels of activated p38 mitogen-activated protein kinase, nuclear factor kappa B, and caspase 3 were lower in the PHC-treated animals. Conclusions: PHC protected rat kidneys from I/R injury by attenuating oxidative stress, inflammatory response, and apoptosis. Thus, PHC may represent a novel practical strategy for the treatment of renal I/R injury. (C) 2014 Elsevier Inc. All rights reserved.