Abstract Background To investigate the mechanism by which Tributyrin (TB) alleviates intestinal inflammation in rats with experimental colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Methods A total of 24 male Sprague-Dawley rats were randomly assigned to four groups (n = 6 per group): the control group, the model group (TNBS group), the TB low-dose group (TNBS + TB 600 mg/kg), and the TB high-dose group (TNBS + TB 1000 mg/kg). The rats in the two TB-treated groups received oral gavage of the respective TB doses daily for one week before and after model induction. Following the establishment of the model, general conditions and fecal characteristics of the rats were monitored, and the disease activity index (DAI) was assessed. After euthanasia, colonic tissues were collected for macroscopic examination, hematoxylin and eosin staining and histological damage scoring. The inflammatory response and outcomes associated with the ferroptosis signaling pathway were evaluated by enzyme-linked immunosorbent assay, western blotting, immunohistochemistry, and biochemical assays. Results Compared to the control group, the TNBS group exhibited significantly increased DAI and histological damage scores, alongside significantly decreased protein expression levels of GPX4 and SLC7A11. Conversely, the expression levels of ACSL4 and FTH1 were elevated. In contrast to the TNBS group, treatment with both low and high doses of TB markedly reduced the DAI and histological damage scores, with the high-dose TB group demonstrating the most pronounced therapeutic effect (all P 0.05). Furthermore, TB reversed the alterations in glutathione and malondialdehyde levels in the intestinal epithelial cells of the TNBS group. It also up-regulated the protein expression of GPX4 and SLC7A11, while simultaneously down-regulating the expression of ACSL4 and FTH1 (all P 0.05). Conclusion TB ameliorates oxidative stress and intestinal inflammatory injury in a TNBS-induced rat model of Crohn’s disease, suggesting that its mechanism is associated with the inhibition of the ferroptosis pathway. Conflict of interest: Ms. Kang, Mei: No conflict of interest Wen, Hongtao: No conflict of interest Han, Bing: No conflict of interest Li, Ya: No conflict of interest
Kang et al. (Thu,) studied this question.