High-intensity interval training alleviates liver inflammation by regulating the TLR4/NF-κB signaling pathway and M1/M2 macrophage balance in female rats with cisplatin hepatotoxicity.

Cisplatin (CDDP) is an antineoplastic drug whose adverse effects include hepatotoxicity. The inflammatory process is crucial in the progression of liver injuries. Exercise is known for its anti-inflammatory effects, but the influence of different training modalities on hepatoprotection is still unclear. This study aims to compare the impacts between preconditioning with high-intensity interval training (HIIT) and traditional continuous training of low (LT) and moderate (MT) intensities on inflammatory markers in Wistar female rats with CDDP-induced hepatotoxicity. Thirty-five rats were divided into five groups: control and sedentary (C + Sed), treated with CDDP and sedentary (CDDP + Sed), treated with CDDP and subjected to LT (CDDP + LT), treated with CDDP and subjected to MT (CDDP + MT), and treated with CDDP and subjected to HIIT (CDDP + HIIT). The training protocols consisted of treadmill running for 8 weeks before CDDP treatment. The rats were euthanized 7 days after the treatment. Liver samples were collected to evaluate the expression of various inflammatory markers and types of macrophages. Our results indicated that HIIT was the only protocol to prevent the increase in all analyzed pro-inflammatory cytokines and reduce the number of ED-1-positive cells, attenuating the TLR4/NF-κB signaling pathway in the liver. Additionally, HIIT increased the anti-inflammatory cytokine IL-10 and regulated M1/M2 macrophage polarization. Thus, this study suggests that preconditioning with HIIT is more effective in promoting hepatoprotective effects than LT and MT, regulating inflammatory markers through modulation of the TLR4/NF-κB signaling pathway and M2 macrophage polarization in the hepatic tissue of female rats treated with CDDP.