Abstract
Objective: The present study was designed to evaluate the effect of hyperhomocysteinemia (Hhcy) induced by feeding rats high methionine diet on the colon wall. Colonic damages caused by Hhcy were compared with those induced by acetic –acid induced colitis.Methods: Sprague-Dawley rats (200-250g) were divided into four groups: group C (control), group M (received 1 g/kg methionine p. o. during 15 d), group A (colitis was induced by transrectal administration of acetic acid 4% on 8th day) and group MA (received methionine and acetic acid). At the end of the study, plasma homocysteine, C-reactive protein (CRP) and leukocytes (WBC) count were evaluated, all rats were sacrificed and distal 8 cm of the colon was dissected. Colon was weighed for disease activity index (DAI) and injuries were assessed macroscopically and histologically.Results: High methionine diet induced significant (P<0.001) increase of homocysteine (hcy), CRP levels and WBC count compared to control. Acetic acid rats showed a significant decrease of WBC count. Mixed treatment caused a significant increase of hcy, CRP and a significant decrease of WBC count. Our results showed that Hhcy causes significant damages and immune cells infiltration in all layers of the colonic wall.Conclusion: The present investigation demonstrated that Hhcy increased the major inflammatory markers as CRP and leukocytes count and produced transmural colitis in rats. Effect of Hhcy is more toxic on the colonic wall than acetic acid indeed while acetic acid lesions are localized in mucosa and submucosa the lesions of hcy extend to the all layers (mucosa, submucosa and muscularis propria). Acetic acid induced colitis in hyperhomocysteinemic rats increased the severity of colitis.
Highlights
Colitis is a term used to describe inflammation of the colon which leads to various changes in the colonic histological organization [1]
Effects of high methionine diet and acetic acid on food intake and body weight Body weight loss was calculated as the percent difference between the original body weight and the body weight on day 3, 5, 7, 9, 11, 13 and 15
Results of MA group showed a significant decrease of WBC compared to acetic acid control (A) and methionine control (M)
Summary
Colitis is a term used to describe inflammation of the colon which leads to various changes in the colonic histological organization [1]. Inflammation is a defensive process that a living body initiates against local tissue damage or the presence of inflammatory stimulants [2]. An immediate and early defensive response in the host to all forms of injury, helps to heal wounds and promote tissue regeneration [3]. When this process of inflammation is not controlled properly via competent negative feedback, a chronic low-grade inflammatory state could result [2]. Recent studies supported the fact that elevation of circulating hcy (the metabolite of methionine) is associated with inflammation [6]. It should be noted that Hhcy is produced from inflammation, but the oxidative stress generated from Hhcy will again promote inflammation [9]
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