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

Area of Science:

• Gastroenterology and Immunology
• Pharmacology and Molecular Biology

Background:

• Ulcerative colitis (UC) involves complex interactions between Nrf-2 and NF-κB pathways, with oxidative damage and inflammation being key features.
• Angiotensin receptor blockers (ARBs) show potential for treating oxidative damage and inflammation, prompting investigation into their role in colitis.

Purpose of the Study:

• To investigate the therapeutic effects of telmisartan (TEL), an ARB, in a rat model of dextran sodium sulfate (DSS)-induced colitis.
• To explore TEL's impact on oxidative stress, inflammation, apoptosis, and the Nrf-2/NF-κB signaling pathways in colitis.

Main Methods:

• Oral administration of TEL (1.75, 3.5, and 7 mg/kg) to rats with DSS-induced colitis.
• Histological analysis of colon tissue, assessment of inflammatory markers (IL-1β, IL-6, TNF-α, IL-10, CRP), neutrophil infiltration, and antioxidant capacity.
• Evaluation of apoptotic signaling (caspase 3), CD36 gene expression, PPARγ activity, and Nrf-2/NF-κB pathway modulation.

Main Results:

• TEL treatment, especially at 7 mg/kg, significantly alleviated histological damage, reduced inflammatory markers, and improved survival and recovery.
• TEL downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, CRP) and upregulated anti-inflammatory IL-10, while also reducing neutrophil infiltration.
• TEL inhibited apoptosis, increased CD36 and Nrf-2/HO-1 gene expression, downregulated NF-κB p65 phosphorylation, and demonstrated PPARγ agonistic activity.

Conclusions:

• Telmisartan exhibits significant anti-inflammatory, antioxidant, and anti-apoptotic effects in DSS-induced colitis, suggesting its therapeutic potential for ulcerative colitis.
• TEL acts as a modulator of Nrf-2/NF-κB interactions and possesses PPARγ agonistic activity, highlighting its multifaceted therapeutic mechanism.
• PPARγ and CD36 may play critical roles in the pathogenesis of colitis, warranting further investigation in human inflammatory bowel diseases (IBDs).