4-Octyl Itaconate Ameliorates Dextran Sodium Sulphate-Induced Ulcerative Colitis via Nrf2 Activation

GONG Duoyun¹, HU Kai², FAN Kerui¹, CHEN Kun¹, ZHANG Li¹, SHEN Yi^1,3*

(¹Department of Pathophysiology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China; ^{2Department of Histology and Embryology, College of Basic M Medical University, Chongqing 400016, China; ³Experimental Teaching Management Center, Chongqing Medical University, Chongqing 400016, China)}

Abstract:

The aim of this study was to investigate the effect of 4-octyl itaconate on ulcerative colitis mice induced by DSS (dextran sulfate sodium). C57BL/6 mice were divided into control group, itaconate group, DSS-treated group and itaconate+DSS-treated group. Body mass, hematochezia, fecal characteristics of mice were daily observed. PAS and TUNEL staining were applied to detect the intestinal mucous secretion and cell apoptosis. The expression of Nrf2 (NF-E2-related factor 2) and NQO1 (quinine oxidoreductase 1) were analyzed by Western blot. Compared with DSS mice, the itaconate+DSS-treated group presented evident improvement on body mass loss, hematochezia, fecal characteristics, colon shortening and other pathological injuries; showing more mucus and decreased TUNEL positive cells; and the expression levels of antioxidant protein were significantly increased. The evaluation was based on body mass loss, colon shortening, DAI score and the intestinal mucosal injury. These results demonstrate that 4-octyl itaconate possess positive effect on DSS-induced ulcerative colitis, and the mechanism may be related to the up-regulation of Nrf2 antioxidant pathway.

CSTR: 32200.14.cjcb.2021.05.0007