Environmental pollutant UV-328 exacerbates chronic colitis and is associated with altered cholesterol metabolism

Abstract

Environmental exposure is increasingly recognized as an important contributor to the onset and progression of inflammatory bowel disease (IBD). Although the benzotriazole ultraviolet stabilizer UV-328 is widely present in environmental matrixes and biological samples, and exhibits broad toxicity across multiple organisms, its intestinal toxicity remains unclear. In this study, we investigated the effects of UV-328 on colitis progression and the underlying mechanisms using a dextran sulfate sodium (DSS)-induced chronic colitis mouse model combined with colonic epithelial NCM460 cells. UV-328 markedly exacerbated DSS-induced colitis, as evidenced by colon shortening, weight loss, increased disease activity, altered goblet cell numbers and tight junction-related markers, aggravated histopathological damage, and enhanced inflammatory responses. Transcriptomic analysis suggested altered cholesterol metabolism following UV-328 exposure. Treatment with the liver X receptor (LXR) agonist GW3965 alleviated inflammatory responses and colonic injury in the DSS + UV-328 group. Our findings suggest that altered cholesterol metabolism, potentially involving LXR signaling, may contribute to the intestinal toxicity of UV-328 and provide new evidence for evaluating the potential health risks associated with long-term exposure to this persistent organic pollutant, particularly in susceptible populations with impaired intestinal homeostasis.