Hydroxyproline Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice: Involvment of the NF-B Signaling and Oxidative Stress.
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SCOPE: Inflammatory bowel disease (IBD) is a chronic disease of gastrointestinal tract in which oxidative stress and overactivation of inflammatory response are implicated. The aim of the present study is to test the hypothesis that hydroxyproline (Hyp), an amino acid with an antioxidative property, attenuates dextran sulfate sodium (DSS)-induced colitis in mice. METHODS AND RESULTS: Male C57BL/6 mice supplemented with or without 1% Hyp are subjected to 2.5% DSS in drinking water to induce colitis. Hyp attenuates the severity of colitis as evidenced by reduced disease activity index scores, decreased myeloperoxidase activity, histological damage, and apoptosis. Furthermore, DSS-induced increases in reactive oxygen species accumulation, TNF- and IL-6 secretion, and malonyldialdehyde activity and a decrease in reduced glutathione in the colon are ameliorated by Hyp. The enhanced phosphorylation of STAT3 and NF-B following DSS administration is mitigated by Hyp, which is also observed in LPS-treated RAW264.7 macrophages. Moreover, the inhibitory effect of Hyp on IL-6 expression is mainly mediated by the NF-B signaling, because the induction of STAT3 and IL-6 by LPS is markedly reversed by Bay11-7085, a specific inhibitor NF-B. CONCLUSION: In summary, Hyp is a critical nutrient with an ability to attenuate DSS-induced colonic damage in mice. This beneficial effect of Hyp is partially mediated by inhibiting the NF-B/IL-6 signaling and the restoration of redox homeostasis.
author list (cited authors)
Ji, Y., Dai, Z., Sun, S., Ma, X., Yang, Y., Tso, P., Wu, G., & Wu, Z.
complete list of authors
Ji, Yun||Dai, Zhaolai||Sun, Shiqiang||Ma, Xiaoshi||Yang, Ying||Tso, Patrick||Wu, Guoyao||Wu, Zhenlong