High-intensity interval training elicits superior effects than continuous training to improve renal redox status via klotho and Nrf2 signaling in female rats with cisplatin nephrotoxicity

Abstract

Oxidative and nitrosative stress are the main mechanisms of nephrotoxicity induced by the chemotherapy cisplatin (CDDP). Exercise training can promote antioxidant effects by activating the Klotho and Nrf2 signaling pathways. We compared the effects of low (LIT), moderate (MIT), and high-intensity interval (HIIT) training protocols on the renal redox status via modulation of klotho and Nrf2 signaling in female rats with CDDP-induced AKI. Wistar rats were divided into five groups (n = 7): sedentary control (C + S); CDDP and sedentary (CDDP + S); CDDP and subjected to LIT (CDDP + LIT); CDDP and subjected to MIT (CDDP + MIT); and CDDP and subjected to HIIT (CDDP + HIIT). The training protocols were carried out on a motorized treadmill lasting 8 weeks. After this period, we administered CDDP (5 mg/kg) and, 7 days later, collected biological samples for analysis. Our data demonstrate that CDDP caused changes to the tubular structure and absorptive function, reduced klotho expression, and increased oxidative and nitrosative damage markers to cellular macromolecules, such as lipids (4-HNE and TBARS), proteins (carbonylation and 3-NT), and DNA (8-OHDG). However, training protocols reduced all of these changes in an intensity-dependent manner, with effects more prominent with HIIT. Our training protocols increased the renal antioxidant defenses (SOD-1, catalase, and GPx), probably through the activation of the Nrf2 pathway, also in an intensity-dependent manner. In conclusion, our results suggest that HIIT promoted more pronounced renoprotective effects than LIT and MIT, improving redox status via activating of the Klotho and Nrf2 signaling pathways in female rats with CDDP-induced nephrotoxicity.