The Effects Of Hydrogen-Rich Water On Colon Colitis/Cancer And Its Mechanisms

In recent years,the morbidity of colorectal cancer increased rapidly because of the changes of people’s dietary structure and living style.In addition,ulcerative colitis(UC)is a chronic non-specific colitis disease.Importantly,patients with long-term chronic UC increased risk of colorectal cancer(CRC).Therefore,it is important to prevent the development of colitis and colon cancer through dietary intervention.Hydrogen-rich water is full of hydrogen,and has multi-bioactivities as antioxidation,anti-inflmmatory etc.In present study,UC and CRC mice models were established using DSS and AOM+DSS,respectively,and the mice were orally administered hydrogen-rich water.The effects of hydrogen-rich water on UC and CRC and its molecular mechanisms were investigated;subcutaneous inoculation of colorectal cancer xenograft mouse model were used to explore the inhibition effects of hydrogen-rich water on the formation of tumor and its molecular mechanisms.The results were as follows:(1)Inhibition effects of hydrogen-rich water on UC and its mechanisms.Compared with the UC model group,the intervention of hydrogen-rich water significantly improved the clinical symptoms of colitis in mice,which included the decreases of bloody stools,diarrhea symptoms,and disease activity index,the recovery of body weight in acute lesions,the decreasing of colon length(by about 0.3cm)in mice.Besides,thymus index was significantly increased in mice(P<0.05).Pathological results showed that hydrogen-rich water significantly reduced the damage to colonic crypts and ameliorated the neutrophil infiltration and hyperplasia.Immunohistochemistry results showed that the hydrogen-rich water significantly inhibited the expression of Ki67 protein.In addition,hydrogen-rich water significantly increased the activities of antioxidant enzymes(SOD(64.1±8.4U/mL),CAT(5.4±0.9U/mL)),the levels of GSH(40.0±13.8μmol/L)and cytokine IL-27(21.8±13.7pg/mL),and decreased level of TNF-α(4.8±1.4pg/mL)(P<0.05).Furthermore,the results of microarray and QPCR validation showed that totally expression of 891 genes significantly changed in UC group in comparison with NC group,whereas the intervention of hydrogen-rich water significantly reduced the amount of abnormal expression of genes to 212(142 up-regulated,70 down-regulated)compared with the UC group.Notably,hydrogen-rich water unregulated 57 genes,17 genes were associated with inflammation,in which 8 genes were related to IFN-γ expression.(2)Inhibition effect of hydrogen-rich water on CRC.Compared with the CRC model group,the intervention of hydrogen-rich water significantly improved the clinical symptoms of colitis in mice,manifested as the decreases of bloody stools,diarrhea symptoms,and disease activity index,the recovery of body weight in acute lesions,and the significant inhibition of colon shortening(by about 0.7cm).Besides,the number of tumors were significantly reduced and the spleen index was significantly improved(P<0.05).Pathological results showed that hydrogen-rich water significantly reduced the damage to colonic crypts,alleviated the neutrophil infiltration and gland hyperplasia.Immunohistochemistry results showed that hydrogen-rich water significantly reduced the expression of Ki67 protein.In addition,hydrogen-rich water significantly increased the levels of TNF-α(15.2±9.0pg/mL)and IL-22(76.0±50.6pg/mL)and lowered the level of IL-27(24.7±14.7pg/mL)(P<0.05).(3)Inhibition effects of hydrogen-rich water on the formation of tumor in tranplanted tumor of mice and its molecular mechanisms.Compared with the control group,the intervention of hydrogen-rich water significantly inhibited tumor growth(P<0.05),reduced the frequency of Ki67 protein,and induced apoptosis(P<0.05).Compared with the control group,hydrogen-rich water significantly decreased the level of GSH,whereas it increased the level of GSSH and the ratio of GSSH/GSH ratio increased to 1.48(P<0.05).The results of genome array and QPCR showed that the intervention of hydrogen-rich water regulated the expression of IFN-gamma-related genes.Conclusion: The hydrogen-rich water could effectively prevent the occurrence and development of UC and CRC by regulating the intracellular oxidation,the inflammation,and the expression of IFN-γ related genes,and then inhibit the proliferation of CRC cell and promote the apoptosis.