Protective Effect And Mechanisms Of Hydrogen-rich Water On Ethanol-induced Gastric And Liver Injury

AimsTo explore the protective effect and mechanisms of hydrogen-rich water(HRW)on ethanol-induced acute gastric injury and chronic liver injury,and the adverse effects of HRW in experimental mice.MethodsModels for acute ethanol-induced gastric injury and chronic ethanol-induced liver injury were established in mice.Mice were divided into four groups: normal control group,HRW group,ethanol model group and HRW treated group.Survival of mice with chronic ethanol liver injury model was observed.Gastric injury was assessed by mucosal injury index in mice with acute ethanol gastric injury model.H&E staining was used to examine the pathological changes of gastric and liver tissues.The serum ALT?AST?TB and DB levels in mice with chronic ethanol liver injury model were measured.The Superoxide Dismutase(SOD)activity in the serum,gastric and liver tissues of mice was measured by WST-1 assay.The Malondialdehyde(MDA)level in serum,gastric and liver tissues of mice was measured by TAB.The mice serum levels of IL-6 and TNF-? were determined by ELISA.The protein and mRNA expressions of Caspase-3,Bax,Caspase-9,Fas and Caspase-8 in gastric and liver tissues were respectively determined by immunohistochemistry and RT-PCR.P < 0.05 was considered statistically significant.Results1.In the acute ethanol-induced gastric injury model,compared to the normal control group,the ethanol model group mice showed a significant increase in the gastric mucosal injury index(P<0.001),significant injury in the gastric tissues,a significant reduction in the oxidative marker serum SOD/MDA(P<0.001),a significant increase in the expression of oxidative marker serum SOD,serum and gastric tissue MDA,inflammatory factor IL-6,apoptotic factors Caspase-3,Bax,Fas protein and Caspase-3,Bax,Fas,Caspase-9 mRNA(P<0.001,P<0.001,P<0.001,P<0.001,P<0.001,P<0.001,P<0.001,P<0.001,P=0.047,P=0.002,P=0.001).Compared to the ethanol model group,treatment of ethanol-fed mice with HRW could significantly reduce the gastric mucosal injury index(P<0.001),improve the gastric tissue damage,show a significant increase in the expression of serum SOD activity(P<0.001),show a significant increase in the expression of serum and gastric tissue SOD/MDA(P=0.002,P<0.001),and there was a significant reduction in the serum and gastric tissue MDA(P<0.001,P<0.001),serum IL-6(P<0.001),as well as the levels of Caspase-3,Bax protein and Caspase-3,Bax,Fas mRNA in the HRW treated group(P<0.001,P<0.001,P<0.001,P=0.005,P<0.001).In addition,there was no significant difference in the gastric mucosal injury index,oxidative index,inflammatory factor and apoptosis factor between normal control group and HRW group(P>0.05).2.In the chronic ethanol-induced liver injury model,compared to the normal control group,the ethanol model group mice showed a significantly worse survival(P<0.001),significant injury in the liver tissues,a significant increase in the expression of serum ALT,AST(P<0.001,P<0.001),a significant reduction in the oxidative marker serum and liver tissue SOD/MDA(P=0.002,P<0.001),a significant increase in the expression of oxidative marker serum and liver tissue MDA,inflammatory factor TNF-?,apoptotic factors Bax,Caspase-8 protein and Fas mRNA(P<0.001,P<0.001,P=0.001,P<0.001,P<0.001,P<0.001).Compared to the ethanol model group,treatment of ethanol-fed mice with HRW could significantly improve the animal survival rate(P=0.019),improve the liver tissue damage,show a significant reduction in the serum ALT and AST(P<0.001,P=0.002),show a significant increase in the expression of liver tissue SOD/MDA(P<0.001),show a significant reduction in the serum and liver tissue MDA(P=0.001,P<0.001),serum TNF-?(P<0.001),and there was no significant difference in the expression of apoptotic factors between ethanol model group and HRW treated group(P> 0.05).In addition,there was no significant difference in the survival rate,serum ALT,AST,TB,DB,oxidative index,inflammatory factor and apoptosis factor between the normal control group and HRW group(P> 0.05).ConclusionsHRW could reduce the degree of ethanol-induced acute gastric injury and chronic liver injury.In the acute ethanol-induced gastric injury model,the possible mechanisms include antioxidant,anti-inflammatory and anti-apoptosis effect of the HRW.In the chronic ethanol-induced liver injury,HRW may exert its protective effect by its antioxidant and anti-inflammatory properties.HRW was safe and reliable with no obvious side effects observed in mice.