Hydrogen-rich water protects against inflammatory bowel disease in mice by inhibiting endoplasmic reticulum stress and promoting heme oxygenase-1 expression.

Abstract

Using a dextran sulfate sodium (DSS)-induced murine model of inflammatory bowel disease (IBD), this study examined the intestinal protective effects of hydrogen-rich water (HRW) and the underlying mechanisms. Male mice were allocated to control, DSS, DSS+HRW, and DSS+HRW+ZnPP groups. HRW administration significantly reduced body weight loss, disease activity index, colon shortening, and colonic wall thickening compared with DSS-only animals. Oxidative stress markers MDA and MPO in colonic tissue were markedly lowered, while superoxide dismutase activity and glutathione levels increased. Pro-inflammatory cytokines TNF-α, IL-6, and IL-1β were substantially reduced. Key endoplasmic reticulum (ER) stress proteins—p-eIF2α, ATF4, XBP1s, and CHOP—were downregulated following HRW administration. HRW also upregulated heme oxygenase-1 (HO-1) expression, and co-administration of the HO-1 inhibitor ZnPP reversed these protective outcomes, implicating the HO-1 pathway as a critical mediator of HRW's effects.

Mechanism

HRW suppresses ER stress signaling proteins (p-eIF2α, ATF4, XBP1s, CHOP) and upregulates HO-1 expression, collectively reducing oxidative stress markers and pro-inflammatory cytokine levels to protect colonic tissue in DSS-induced IBD.