• Adam Khader, Weng-Lang Yang, Michael Kuncewitch, Jose M Prince, Philippe Marambaud, Jeffrey Nicastro, Gene F Coppa, and Ping Wang.
• Elmezzi Graduate School of Molecular Medicine, Manhasset, New York; Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York; Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, New York.
• J. Surg. Res. 2015 Feb 1;193(2):807-15.

BackgroundRenal ischemia-reperfusion (I/R) is a severe clinical complication with no specific treatment. Resveratrol has been shown as a promising experimental agent in renal I/R due to its effect on cellular energy metabolism, oxidative stress, and inflammation. Recently, we identified two biologically active resveratrol analogues (RSVAs), RSVA405 and RSVA314. We hypothesized that both RSAVs would attenuate I/R-induced renal injury.MethodsAdult male rats were subjected to renal I/R through bilateral renal pedicle clamping for 60 min, followed by reperfusion. RSVA405 (3 mg/kg Body Weight), RSVA314 (3 mg/kg Body Weight), or vehicle (10% dimethyl sulfoxide and 33% Solutol in phosphate buffered saline) were administered by intraperitoneal injection 1 h before ischemia. Blood and renal tissues were collected 24 h after I/R for evaluation.ResultsAdministration of RSVA405 and RSVA314 significantly reduced the serum levels of renal dysfunction and injury markers, including creatinine, blood urea nitrogen, aspartate aminotransferase, and lactate dehydrogenase, compared with vehicle. The protective effect of RSVA405 and RSVA314 was also reflected on histologic evaluation. Both RSVAs reduced the number of apoptotic cells by more than 60% as determined by transferase dUTP nick end labeling assay, compared with vehicle. The renal adenosine triphosphate levels of the vehicle group was decreased to 52.4% of control, whereas those of the RSVA405 and RSVA314 groups were restored to 72.3% and 79.6% of control, respectively. Both RSVAs significantly reduced the protein expression of inducible nitric oxide synthase and nitrotyrosine and the messenger RNA levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β.ConclusionsRSVA405 and RSVA314 attenuate I/R-induced renal injury through the modulation of energy metabolism, oxidative stress, and inflammation.Copyright © 2015 Elsevier Inc. All rights reserved.

35 keywords...

hide…