Hepatorenal protection during renal ischemia by quercetin and remote ischemic perconditioning Firouzeh Gholampour, PhD,* and Zahra Sadidi, MSc Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran article info Article history: Received 17 February 2018 Received in revised form 15 April 2018 Accepted 23 May 2018 Available online xxx Keywords: Oxidative stress Quercetin Reperfusion injury Remote ischemic perconditioning abstract Background: Pathogenesis of renal ischemia/reperfusion injury (IRI) involves oxidative stress response in the kidney and remote organs. Both quercetin and remote ischemic perconditioning (RIPerC) can protect partially against IRI. This study determined whether combined quercetin and RIPerC could provide an augmented hepatorenal protection against renal IRI. Materials and methods: I/R was induced by clamping renal arteries for 45 min followed by 24- h reperfusion. RIPerC consisted of four cycles of 2 min of left femoral artery ischemia followed by 3 min of reperfusion administered at the beginning of renal ischemia. Rats were divided into five groups: sham, I/R, RIPerC, quercetin (Q þ I/R), and combined quer- cetin and RIPerC (Q þ RIPerC). At the end of reperfusion period, blood, urine, and tissue samples were collected. Results: I/R caused kidney dysfunction, as proved by significant decrease in creatinine clearance, and a significant increase in liver functional indicators as evidenced by increased plasma alanine aminotransferase and aspartate aminotransferase activity. This was accompanied by a decrease of glutathione peroxidase and catalase activities with an increase of malondialdehyde levels and histological damages in renal and hepatic tissues. Treatment with RIPerC and quercetin reduced all these changes. However, the measure of improvements was enhanced by combined quercetin and RIPerC treatment. Conclusions: This study demonstrated protective effects of quercetin and RIPerC strategy on the both kidney and liver after renal I/R. The results suggest that combined quercetin and RIPerC provides an enhanced protection against renal IRI by reduction of lipid peroxidation and augmentation of antioxidant systems. ª 2018 Elsevier Inc. All rights reserved. Introduction It is well known that renal ischemia results in tissue injury and kidney dysfunction. Ischemic kidney injury is generally attributed to tissue hypoxia and consequently to the depletion of cellular ATP. 1 Reperfusion, although serves to minimize the magnitude of the hypoxic insult, results in a unique type of injury response that is commonly called “reperfusion injury”. Reperfusion injury reduces the gain of renal reperfusion and paradoxically leads to renal dysfunction. 2 Besides, liver injury has been seen after reperfusion of ischemic kidney, which proposes that different interorgan pathways from ischemic kidney mediate remote organ injuries. Thus many basic and clinical researches have been focused to limit the ischemia/ reperfusion injury (IRI). It has been shown that ischemic pre- conditioning can protect robustly against renal IRI, 3 but it has * Corresponding author. Department of Biology, School of Sciences, Shiraz University, Shiraz, Iran. Tel.: þ98 7136137362; fax: þ98 7132280916. E-mail address: gholampour@shirazu.ac.ir (F. Gholampour). Available online at www.sciencedirect.com ScienceDirect journal homepage: www.JournalofSurgicalResearch.com journal of surgical research  november 2018 (231) 224 e233 0022-4804/$ e see front matter ª 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jss.2018.05.036