Sex-dependent responses in mice to indomethacin-induced organ injury and gut microbiome-targeted alleviation.

ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used widely but produce gastrointestinal (GI) toxicities in both short- and long-term users. Previous studies have shown that the intestinal microbiota play an important role in gut damage and that gut microbial β-glucuronidase (GUS) inhibitors can alleviate NSAID-induced injury in male mice by blocking the GI reactivation of NSAID-glucuronides. Here, in both male and female C57BL/6 mice, we examine the effects of indomethacin alone and with the GUS inhibitor UNC10201652. Oral delivery of 5 mg/kg body weight indomethacin over 5 days decreased body weight, induced colonic and hepatic inflammatory cytokine gene expression, and enlarged the spleens of both male and female mice. However, sex-specific inflammatory responses to indomethacin were

SUBMITTER: Zhang J 

PROVIDER: S-EPMC12528479 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature