The role of the physical exercise in renal injury induced by cisplatin

• Grant number: 11/10349-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2011
• End date: December 31, 2013
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Mariana Yasue Saito Miyagi
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 12/17045-4 - The role of heme oxygenase-1 over the receptors ADORA-2A and 2B in renal ischemia-reperfusion injury model, BE.EP.IC

Abstract

Cisplatin is a chemotherapy drug widely used in the treatment of many types of cancer, which has the use limited by side effects as, among others, cachexia and nephrotoxicity. The use of cisplatin also increases TNFa - a pro-inflammatory cytokine - levels in kidney, serum and urine. Since studies have shown that physical exercises reduces the production of pro-inflammatory substances such as TNFa, the aim of this study is to verify the impact of physical exercise in the immune system, analyzing the extent of its benefits in the model of cisplatin-induced renal injury. Cisplatin toxicity will be induced by a single intraperitoneal dose of 20 mg/kg in C57Bl6 mice, which will be sacrificed 96 hours after administration. Serum and renal tissue will be collected, in addition to fat, liver and muscle of the animals for analysis of morphological, metabolic and molecular states. Unmanipulated animals from each group will be used as controls. The physical exercise will be performed in a treadmill adapted for mice, and all animals will have one week of adaptation. In order to evaluate the effect of cisplatin in acute training, we will start the training after adaptation, and continue until the first day after injection of cisplatin. In order to evaluate the effect of cisplatin in chronic exercise, we will proceed with the exercise during 6 weeks, until the first day after injection. After sacrifice, we will analyze renal injury by urea and creatinine levels in the serum, and by kidney histological analysis. The evaluation of pro-inflammatory cytokines will be done by their dosage in renal tissue by Bioplex method and their gene expressions, by real time RT-PCR. Thus, this project aims to evaluate the influence of physical exercise on chemotherapy side effects through an immunological view, which may have future clinical applications.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SAITO MIYAGI, MARIANA YASUE; LATANCIA, MARCELA TEATIN; TESTAGROSSA, LEONARDO ABREU; DE ANDRADE-OLIVEIRA, VINICIUS; PEREIRA, WELBERT OLIVEIRA; HIYANE, MEIRE IOSHIE; ENJIU, LUCAS MACERATESI; PISCIOTTANO, MARCUS; LEITE SEELAENDER, MARILIA CERQUEIRA; SARAIVA CAMARA, NIELS OLSEN; et al. Physical exercise contributes to cisplatin-induced nephrotoxicity protection with decreased CD4+T cells activation. Molecular Immunology, v. 101, p. 507-513, SEP 2018. (12/50079-0, 11/10349-5, 12/10435-1, 12/02270-2)

SAITO MIYAGI, MARIANA YASUE; SEELAENDER, MARILIA; CASTOLDI, ANGELA; DE ALMEIDA, DANILO CANDIDO; NOVA BACURAU, ALINE VILLA; ANDRADE-OLIVEIRA, VINICIUS; ENJIU, LUCAS MACERATESI; PISCIOTTANO, MARCUS; HAYASHIDA, CAROLINE YURI; HIYANE, MEIRE IOSHIE; et al. Long-Term Aerobic Exercise Protects against Cisplatin-Induced Nephrotoxicity by Modulating the Expression of IL-6 and HO-1. PLoS One, v. 9, n. 10, OCT 1 2014. (12/50079-0, 12/10435-1, 12/02270-2, 11/10349-5)