New α-Lipoic Acid Derivative, DHL-HisZn, Ameliorates Renal Ischemia-Reperfusion Injury in Rats

Abstract

Ischemia-reperfusion (I/R) occurs frequently in a variety of clinical settings, such as renal transplantation. In addition, I/R is a major cause of acute kidney injury (AKI). A recent study has reported that reactive oxygen species (ROS) are important mediators of AKI, suggesting that reducing ROS generation may prevent renal injury. The present study evaluated the ability of DHL-HisZn, a new α-lipoic acid derivative, to inhibit ROS generation and prevent renal I/R injury in rats. Rats received an intravenous infusion of DHL-HisZn or saline, and then underwent experimentally induced renal I/R injury or sham treatment. Rats were sacrificed after 60 min of ischemia and 24 h of reperfusion. To evaluate the renal protective effects of DHL-HisZn, serum blood urea nitrogen (BUN) and creatinine (Cre) concentrations were determined, kidneys were histologically assessed, and malondialdehyde (MDA), a biomarker of oxidative stress, was evaluated. In addition, antimycin A (AMA)-stimulated RAW264.7 cells were treated with DHL-HisZn to assess its antioxidant effects in vitro. DHL-HisZn treatment attenuated I/R-induced histologic alterations, reduced serum levels of serum BUN and Cre, and decreased MDA levels in the kidneys of rats with renal I/R injury. Furthermore, DHL-HisZn decreased ROS levels in AMA-stimulated RAW264.7 cells. Our in vitro and in vivo findings suggest that DHL-HisZn may have therapeutic potential against various human I/R conditions.