Efeitos do treinamento aeróbico moderado sobre o estado redox, a inflamação e a apoptose renais na injúria renal aguda induzida pela gentamicina em ratos

Abstract

Aerobic exercise has been increasingly used as a therapeutic agent in several diseases, including kidney disorders. However, the mechanisms playing a renoprotective role in physical exercise are still unclear. Additionally, there are few studies targeted at investigating whether trained individuals are powered with some renal protection in case they develop acute kidney injury (AKI). In the present study it was evaluated the effects of training prior to gentamicin (GM)-induced AKI on renal function, morphology, redox status, inflammation and apoptosis in rats. Male Wistar rats were submitted to a moderate aerobic training protocol for 8 weeks prior to treatment with GM (80mg/kg/day/5 days) or 0.9% NaCl (saline) (CEUA/UFMG, protocol #46/2014). Rats were divided into 4 groups: not trained and trained rats treated with saline (NT-SAL and T-SAL groups), not trained and trained rats treated with GM (NT-GM and T-GM groups) (n = 5-7). Blood pressure and heart rate were measured before and after training. Doppler ultrasonography of renal arteries and echocardiography were performed at the end of treatments. Samples of urine, blood and tissues were collected for biochemical and histological studies. Trained rats exhibited higher physical performance and muscular oxidative adaptation than not trained rats. Training did not induce any change in blood pressure, cardiac function, renal perfusion and renal energetic metabolism (gene expression of PPAR-α and PGC1-α). Training prior to GM-induced AKI attenuated the increase in plasma creatinine, proteinuria and the reduction in glomerular filtration rate and urinary osmolality. Training also decreased the severity of renal tissue damage, increased the level of urinary hydroperoxides and expression of Nrf2 (transcription factor related to the anti-oxidant response), prevented the reduction of catalase activity, attenuated the increse in renal levels of TNF-α, IL-1β, IL-6, inhibited expression of NFκB (transcription factor related to inflammation) and prevented the expression increase of renal caspase 8 and Bax. It was concluded that aerobic training prior to AKI induced by GM has attenuated renal morphofunctional damage by reducing inflammation and expression of pro-apoptotic factors. It is possible that increased production of reactive oxygen species by training induces a higher expression of Nrf2, which may play a central role in training-mediated renoprotection, by inhibiting NFκB and thereby reducing proinflammatory and pro-apoptotic signaling in the kidneys.