title: Long-term aerobic exercise protects against cisplatin-induced nephrotoxicity by modulating the expression of IL-6 and HO-1.
abstract: 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.
authors.affiliation: Laboratory of Immunobiology of Transplants, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Mariana Yasue Saito
authors.initials: MY
authors.lastname: Miyagi
authors.affiliation: Cancer Metabolism Research Group, Department of Cell Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Marilia
authors.initials: M
authors.lastname: Seelaender
authors.affiliation: Laboratory of Immunobiology of Transplants, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Angela
authors.initials: A
authors.lastname: Castoldi
authors.affiliation: Laboratory of Immunobiology of Transplants, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Danilo Candido
authors.initials: DC
authors.lastname: de Almeida
authors.affiliation: Laboratory of Molecular and Cellular Exercise Physiology, School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Aline Villa Nova
authors.initials: AV
authors.lastname: Bacurau
authors.affiliation: Laboratory of Immunobiology of Transplants, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Vinicius
authors.initials: V
authors.lastname: Andrade-Oliveira
authors.affiliation: Cancer Metabolism Research Group, Department of Cell Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Lucas Maceratesi
authors.initials: LM
authors.lastname: Enjiu
authors.affiliation: Cancer Metabolism Research Group, Department of Cell Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Marcus
authors.initials: M
authors.lastname: Pisciottano
authors.affiliation: Laboratory of Immunobiology of Transplants, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Caroline Yuri
authors.initials: CY
authors.lastname: Hayashida
authors.affiliation: Laboratory of Immunobiology of Transplants, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Meire Ioshie
authors.initials: MI
authors.lastname: Hiyane
authors.affiliation: Laboratory of Molecular and Cellular Exercise Physiology, School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Patricia Chakur
authors.initials: PC
authors.lastname: Brum
authors.affiliation: Laboratory of Immunobiology of Transplants, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Niels Olsen Saraiva
authors.initials: NO
authors.lastname: Camara
authors.affiliation: Laboratory of Immunobiology of Transplants, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Mariane Tami
authors.initials: MT
authors.lastname: Amano
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002100:Cachexia / Q000209:etiology / Q000517:prevention & control; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D010805:Physical Conditioning, Animal; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D048069:Tumor Necrosis Factors; D051547:Heme Oxygenase-1; D002945:Cisplatin