Resveratrol attenuated high intensity exercise training-induced inflammation and ferroptosis via Nrf2/FTH1/GPX4 pathway in intestine of mice

Authors: ZHE XU, XIAONAN SUN, BIN DING, MING ZI, YAN MA

Abstract: Background/aim: Moderate exercise has beneficial effects for human health and is helpful for the protection against several diseases. However, high intensity exercise training caused gastrointestinal syndrome. Resveratrol, a plant extract, plays a vital role in protecting various organs. However, whether resveratrol protected mice against high intensity exercise training-induced intestinal damage remains unclear. In this study, our objective was to investigate the protective effects and mechanism of resveratrol in high intensity exercise training-treated mice. Materials and methods: Mice were treated with swimming exercise protocol and/or resveratrol (15 mg/kg/day) for 28 consecutive days. Then, the mice were sacrificed, and a series of evaluation indicators, including inflammatory factors and intestinal permeability of the gut, were measured based on this model. The expressions of inflammatory factors (tumor necrosis factor (TNF)-α; interferon (IFN)-α, interleukin (IL)-6 and IL-10), oxidative stress (Nrf2, glutathione (GSH), hydrogen peroxide (H2O2), catalase (CAT) and malondialdehyde (MDA)), intestinal barrier (gut permeability, ZO-1, Occludin and Claudin-1 as well as ferroptosis (Fe2+, Fe3+, SLC7A11, glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1)) were measured, respectively. Results: High intensity exercise training induced colon damage, manifested as inflammation (increased TNF-α, IFN-γ and IL-6 concentrations, and decreased IL-10 concentration), oxidative stress (the increase of H2O2 and MDA concentration, and the reduced CAT and GSH activities), intestinal barrier injury (increased gut permeability and intestinal fatty-acid binding protein concentration, and inhibited ZO-1, Occludin and Claudin-1 expressions) and ferroptosis (the increased of Fe2+ and Fe3+ concentrations, and suppressed phosphorylated Nrf2, SLC7A11, GPX4 and FTH1), which was relieved by resveratrol treatment in mice. Conclusion: Resveratrol attenuated high intensity exercise training-induced inflammation and ferroptosis through activating Nrf2/ FTH1/GPX4 pathway in mouse colon, which providing new ideas for the prevention and treatment of occupational disease in athlete.

Keywords: Resveratrol, high intensity exercise training, ferroptosis, inflammation, Nrf2/FTH1/GPX4 pathway

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