Hydrogen-Rich Water Mitigates LPS-Induced Chronic Intestinal Inflammatory Response in Rats via Nrf-2 and NF-κB Signaling Pathways

SIMPLE SUMMARY: Our study provides substantial evidence that hydrogen-rich water can prevent intestinal damage caused by LPS-induced stimulation. Intestinal injury caused by LPS is related to the NFκB signaling pathway. LPS promotes the generation of inflammatory factors and oxygen free radicals by activating the NFκB signaling pathway in intestinal cells, causing inflammation and oxidative stress and destroying the tight-junction state of the intestine, causing intestinal damage. Hydrogen-rich water can activate the Nrf-2 signaling pathway to remove excess oxygen free radicals and relieve oxidative stress. The Nrf-2 signaling pathway, an upstream signaling pathway of NFκB, can act as a protective mechanism against inflammation by regulating NFκB. In summary, hydrogen-rich water can inhibit oxidative stress and regulate NF by activating Nrf-2 signal pathway κB signal pathway, inhibit the production of inflammatory cytokines, maintain the tight connection in the intestine, and protect the intestine from damage caused by lipopolysaccharide. Our research contributes to further understanding of the mechanism of hydrogen-rich water, as well as its value for clinical application. ABSTRACT: Long-term exposure to low-dose lipopolysaccharide can impair intestinal barriers, causing intestinal inflammation and leading to systemic inflammation. Hydrogen-rich water possesses antioxidant and anti-inflammatory functions and exerts inhibitory effects on various inflammatory diseases. In this study, we investigated whether oral hydrogen-rich water could prevent lipopolysaccharide-induced chronic intestinal inflammation. An experimental model was established by feeding hydrogen-rich water, followed by the injection of lipopolysaccharide (200 μg/kg) in the tail vein of rats after seven months. ELISA, Western blot, immunohistochemistry, and other methods were used to detect related cytokines, proteins related to the NF-κB and Nrf-2 signaling pathways, and tight-junction proteins to study the anti-inflammatory and antioxidant effects of hydrogen-rich water. The obtained results show that hydrogen-rich water significantly increased the levels of superoxide dismutase and structural proteins; activated the Nrf-2 signaling pathway; downregulated the expression of inflammatory factors cyclooxygenase-2, myeloperoxidase, and ROS; and decreased the activation of the NF-κB signaling pathway. These results suggest that hydrogen-rich water could protect against chronic intestinal inflammation in rats caused by lipopolysaccharide-induced activation of the NF-κB signaling pathway by regulating the Nrf-2 signaling pathway.