Telmisartan ameliorates dextran sodium sulfate-induced colitis in rats by modulating NF-κB signalling in the context of PPARγ agonistic activity.

Variations in Nrf-2 and NF-κB expression profiles have been reported in ulcerative colitis (UC), in which an interplay between these two critical pathways has been identified. The therapeutic potential of angiotensin receptor blockers (ARBs) for oxidative damage and inflammation has recently received considerable attention. Dextran sodium sulfate (DSS)-induced colitis in rats closely resembles human UC and is associated with oxidative damage and the production of pro-inflammatory mediators. Therefore, we aimed to investigate the effect of orally administered telmisartan (TEL) (1.75, 3.5 and 7 mg/kg) in a rat model of DSS-induced colitis. Our study revealed that TEL, particularly at 7 mg/kg, alleviated tissue injury and inflammatory signs upon histological analysis and enhanced survival and recovery during DSS-induced colitis. The levels of colonic IL-1β, IL-6, TNF-α and serum C-reactive protein (CRP) were downregulated, while the level of colonic IL-10 was upregulated. TEL repressed DSS-induced neutrophil infiltration and improved the colonic antioxidant defence machinery. TEL inhibited apoptotic signalling as indicated by lower caspase 3 expression, increased CD36 gene expression and exhibited PPARγ agonistic activity. In addition, TEL downregulated gene expression and inhibited phosphorylation of the NF-κB p65 subunit. On the other hand, TEL upregulated the gene expression of Nrf-2 and HO-1. We concluded that TEL, besides its PPARγ agonistic activity, acted as a modulator of Nrf-2/NF-κB interactions and exhibited anti-apoptotic activity after tissue damage and that PPARγ and CD36 might play a critical role in the pathogenesis of murine colitis. Therefore, our findings suggest that further investigations on human IBDs are warranted.