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

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.

Molsidomine alleviates acetic acid-induced colitis in rats by reducing oxidative stress, inflammation and apoptosis.

Ulcerative colitis (UC) is a subcategory of intestinal inflammatory bowel disease characterized by up-regulation of proinflammatory cytokines and oxidative stress. The current study was designed to assess the probable protective effect of the nitric oxide (NO) donor, molsidomine, in experimental colitis model in rats. Rats were haphazardly classified into four groups: control, acetic acid, acetic acid + molsidomine (1 mg/kg) and acetic acid + molsidomine (2 mg/kg). Molsidomine (1 and 2 mg/kg/day) was administered by intra-peritoneal injection for 7 days prior to induction of UC. On the 8th day, colitis was induced by intra-rectal instillation of 2 ml of (4% v/v) acetic acid in normal saline using a pediatric plastic catheter. The rats were sacrificed 1 day following colitis induction, blood samples were obtained; colons and livers were isolated then underwent macroscopic, biochemical, histopathological and immunohistochemical examination. Pretreatment with molsidomine significantly reduced disease activity index, colon mass index, colonic macroscopic and histological damage. Besides, molsidomine significantly reduced the serum levels of alanine transaminase (ALT) (58.7 ± 8.9 & 59.7 ± 8 vs 288.75 ± 31.4 in AA group) and aspartate transaminase (AST) (196.2 ± 37.4 & 204 ± 30 vs 392.7 ± 35.6 in AA group). Moreover, molsidomine effectively decreased malondialdehyde (MDA) and total nitrate/nitrite (NOx) contents, and up regulated the enzymatic activity of superoxide dismutase (SOD) and glutathione level (GSH) in colonic and hepatic tissues. With regard to anti-inflammatory mechanisms, molsidomine suppressed tumor necrosis factor-alpha (TNF-α) (792.5 ± 16.7 & 448 ± 12.1 vs 1352.5 ± 45.8 in AA group) in colonic tissues and (701 ± 19 & 442.5 ± 22.5 vs 1501 ± 26 in AA group) in hepatic tissues as well as nuclear transcription factor kappa B (NF-kB/p65) levels (416.2 ± 4.1 & 185.5 ± 14.2 vs 659.2 ± 11.5 in AA group) in colonic tissues and (358 ± 6.2 & 163.5 ± 9.6 vs 732.5 ± 5.5 in AA group) in hepatic tissues. In addition, molsidomine significantly decreased inducible nitric oxide synthase (iNOS) levels (8.1 ± 0.1 & 4.9 ± 0.1 vs 16 ± 0.1 in AA group) in colonic tissues and (8.6 ± 0.3 & 6.1 ± 0.1 vs 17.8 ± 0.1 in AA group) in hepatic tissues, and myeloperoxidase (MPO) contents (10.5 ± 0.4 & 6.6 ± 0.3 vs 20.9 ± 0.6 in AA group) in colonic tissues and (13.1 ± 0.2 & 6.3 ± 0.06 vs 23.9 ± 1.4 in AA group) in hepatic tissues at p > 0.05. Furthermore, it suppressed apoptosis by reducing expression of Caspase 3 and Bax in colonic and hepatic tissues. Therefore, molsidomine might be a promising candidate for the treatment of UC.