P0100 Role of Ethyl Pyruvate on Large Intestinal Inflammatory and Oxidative Markers in TNBS-Induced Colitis

Abstract Background Ethyl pyruvate (EP), with anti-inflammatory and antioxidant effects, has shown therapeutic potential in inflammation models. This study examined EP’s effects on inflammatory and oxidative markers in the large intestine using a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rat model. Methods Rats were divided into five groups: Control, EP, Colitis, Pre-colitis and Post-colitis. Large intestine damage was evaluated histopathologically. Tissue levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17), interleukin-10 (IL-10), interleukin-1 (IL-1), Nuclear Factor kappa B (NFκB), inducible nitric oxide synthase (iNOS), and total antioxidant capacity (TAC) were measured by ELISA. Results Our study showed that pre- and post-EP administration decreased damage scores of macroscopic and microscopic in TNBS-induced colitis. (p < 0.01). Tissue MMP-9 and MMP-2 levels significantly increased in the Colitis group compared to the Control, EP, and Post-colitis groups (p < 0.01), while both markers were significantly reduced in the Post-colitis group (p < 0.01). NFκB and iNOS levels were elevated in the Colitis and Pre-colitis groups but significantly decreased in the Post-colitis group (p < 0.05). TAC levels were highest in the Post-colitis group compared to Control (p < 0.05). IL-17 and IL-1 were significantly increased in the Colitis group versus all others (p < 0.05). Conclusion EP demonstrated both protective and therapeutic effects in TNBS-induced colitis by reducing pro-inflammatory markers (MMP-2, MMP-9, NFκB, iNOS, IL-1, IL-17) and enhancing TAC in large intestinal tissue. These findings suggest that EP may be a promising agent in modulating intestinal inflammation and oxidative stress associated with colitis. References: 1.Du L, Ha C. Epidemiology and pathogenesis of ulcerative colitis. Gastroenterol Clin North Am. 2020;49(4):643–54. 2.Koprivica I, Djedovic N, Stojanović I, Miljković Đ. Ethyl pyruvate, a versatile protector in inflammation and autoimmunity. Inflamm Res. 2022;71(2):169–82. 3.Miljković D, Blaževski J, Petković F, et al. A comparative analysis of multiple sclerosis-relevant anti-inflammatory properties of ethyl pyruvate and dimethyl fumarate. J Immunol. 2015;194(6):2493–503. 4.Algien F, Rodriguez-Nogales A, Garrido-Mesa J, et al. Intestinal anti-inflammatory activity of calcium pyruvate in the TNBS model of rat colitis: comparison with ethyl pyruvate. Biochem Pharmacol. 2026;103:53-63. Conflict of interest: Prof. Yorulmaz, Elif: No conflict of interest Yorulmaz, Hatice: No conflict of interest Ozkok, Elif: No conflict of interest Kucuk, Suat Hayri: No conflict of interest Sunger, Erdem: No conflict of interest Ebrahimi, Ayyub: No conflict of interest Yılmaz, Beyza: No conflict of interest Altınay, Serdar: No conflict of interest