Benefícios do treinamento intervalado de alta intensidade comparado a treinamentos contínuos na redução de marcadores apoptóticos nos rins de ratas com nefrotoxicidade induzida por cisplatina – possível papel modulador da IL-11

Abstract

Cisplatin (CP) is an antineoplastic widely used in the treatment of different types of solid tumors, but its use is mainly limited by high nephrotoxicity, which is manifested by acute kidney injury (AKI). The pathophysiology of ARF is complex and involves, among other controls, the activation of several apoptotic signal pathways. On the other hand, some studies have shown protective effects of aerobic exercise on ARF. Furthermore, mechanical stress is

known to increase the production of IL-11, a pleiotropic cytokine with anti-apoptotic and anti- necrotic effects. Thus, the aim of the present study was to compare the impact of high intensity

interval training (HIIT) with continuous light (LIT) and moderate intensity (MIT) training on renal IL-11 levels and expressions of apoptotic markers in tissue renal rate of CP-induced nephrotoxicity. For this purpose, 35 female Wistar rats were divided into five groups (n=7 in each group): control and sedentary (C+S); treated with CP and sedentary (CP+S); treated with CP and approved to LIT (CP+LIT); CP-treated and MIT-approved (CP+MIT) and CP-treated and HIIT-approved (CP+HIIT). Training protocols consisted of running on a motorized treadmill, 5 days a week, for 8 weeks. At the end of the 8 weeks of training, the rates received a single injection of CP (5 mg/kg) or saline solution, and 7 days after the injection they were euthanized. Serum samples and animal rinses were collected to assess serum urea urea (BUN), TNF receptor 1 (TNFR1) and 2 (TNFR2) gene expression, caspase-3, MAPK(p38) (MAPK14), p53, Bax, Bak, Bcl-2 and Bcl-xL, renal IL-11, IL-8 and p53 levels, and immunolocalization of cleaved caspase-3, Bax, Bcl-2 and MAPK(p38) in renal tissue. The data reveal that all trained groups experience a significant increase in renal IL-11 levels associated with reduced local expression of pro-apoptotic markers and increased anti-apoptotic markers. Such effects were dependent on training intensity, and therefore more pronounced with HIIT. In conclusion, the present study suggests that HIIT seems to provide superior renoprotection to continuous training at mild and moderate intensities, beneficially modulating apoptotic signal pathways, and consequently attenuating ARF induced by CP in this experimental model. Furthermore, such an effect may be related, at least in part, to the increase in the renal levels of IL-11 induced by training, also dependent on its intensity.