Long-Term Aerobic Exercise Protects against Cisplatin-Induced Nephrotoxicity by Modulating the Expression of IL-6 and HO-1

PLOS ONE, October 2014

25272046

Mariana Yasue Saito Miyagi, Marilia Seelaender, Angela Castoldi, Danilo Candido de Almeida, Aline Villa Nova Bacurau, Vinicius Andrade-Oliveira, Lucas Maceratesi Enjiu, Marcus Pisciottano, Caroline Yuri Hayashida, Meire Ioshie Hiyane, Patricia Chakur Brum, Niels Olsen Saraiva Camara, Mariane Tami Amano

Nephrotoxicity is substantial side effect for 30% of patients undergoing cancer therapy with cisplatin and may force them to change or even abandon the treatment. Studies regarding aerobic exercise have shown its efficacy for the treatment of many types of diseases and its capacity to reduce tumors. However, little is known about the impact of physical exercise on cisplatin-induced acute kidney injury (AKI). In the present study, our aim was to investigate the role of physical exercise in AKI induced by cisplatin. We submitted C57Bl6 male mice to seven weeks of chronic exercise on a training treadmill and treated them with single i.p. injection of cisplatin (20 mg/kg) in the last week. Exercise efficacy was confirmed by an increased capillary-to-fiber ratio in the gastrocnemius muscle of exercised groups (EX and CIS-EX). The group submitted to exercise before cisplatin administration (CIS-EX) exhibited less weight loss and decreased serum urea levels compared to the cisplatin group (CIS). Exercise also showed a protective role against cisplatin-induced cell death in the kidney. The CIS-EX group showed a lower inflammatory response, with less TNF and IL-10 expression in the kidney and serum. In the same group, we observed an increase of IL-6 and HO-1 expression in the kidney. Taken together, our results indicate that chronic aerobic exercise is able to attenuate AKI by inducing IL-6 and HO-1 production, which results in lower inflammatory and apoptotic profiles in the kidney.