Flavocoxid halts both intestinal and extraintestinal alterations in acetic acid-induced colitis in rats.

Abstract

Ulcerative colitis (UC) is an idiopathic chronic inflammatory disorder mainly affecting the colon and rectum. The present investigation was undertaken to evaluate the potential protective effect of flavocoxid, a dual COX and LOX inhibitor, in colitis model in rats. UC was induced by instillation of 2 ml of 4% acetic acid (AA) into the colon using a pediatric catheter in rats, and flavocoxid (10 and 20 mg·kg-1) was given once daily for 7 days before induction of colitis. Rats were sacrificed; sera were collected; colons and livers were isolated and then analyzed by biochemical, macroscopic, and histopathological examination. Pretreatment with flavocoxid (10 and 20 mg·kg-1) significantly reduced serum levels of alanine transaminase (ALT) (43.7 ± 7 and 76.2 ± 7.3 vs. 288.7 ± 31.4 in AA group) and aspartate transaminase (AST) (179.5 ± 22.2 and 200.5 ± 14 vs. 392.7 ± 35.6 in AA group) (p>0.05). Also, it decreased malondialdehyde (MDA) and nitric oxide (NOx) levels in both colonic and hepatic tissues. Moreover, flavocoxid effectively elevated colonic and hepatic reduced glutathione (GSH) level and superoxide dismutase (SOD) activity when compared to AA group (p>0.05). Additionally, flavocoxid significantly decreased levels of tumor necrosis factor-α (TNF-α) (878.2 ± 13.4 and 560.1 ± 2.9 vs. 1378.1 ± 31 in AA group) in colonic tissues and (701 ± 6.9 and 442.5 ± 8.2 vs. 1501 ± 9.4 in AA group) in hepatic tissues, nuclear factor kappa B (NF-κBp65) (493.8 ± 6.8 and 368.7 ± 3.1 vs. 659.2 ± 9.4 in AA group) in colonic tissues and (358 ± 5.1 and 163.5 ± 7.8 vs. 732.5 ± 4.5 in AA group) in hepatic tissues, myeloperoxidase (MPO) (15.7 ± 0.3 and 13 ± 0.2 vs. 20.9 ± 0.5 in AA group) in colonic tissues and (20.4 ± 0.3 and 16.3 ± 0.3 vs. 23.9 ± 1.2 in AA group) in hepatic tissues, and inducible nitric oxide synthase (iNOS) (12.5 ± 0.3 and 10 ± 0.2 vs. 16 ± 0.1 in AA group) in colonic tissues and (14.1 ± 0.04 and 11.5 ± 0.08 vs. 17.8 ± 0.1 in AA group) in hepatic tissues (p>0.05). Furthermore, it down-regulated Bax and caspase-3 expression in colonic and hepatic tissues upon comparison with AA group. Collectively, flavocoxid conferred a protective impact against acetic acid-induced colitis in rats via attenuating oxidative stress, inflammation, and apoptosis.