Effect of homocysteine on intestinal permeability in rats with experimental colitis, and its mechanism

OBJECTIVE To investigate the effect of homocysteine (Hcy) on intestinal permeability in rats with TNBS/ethanol-induced colitis and elucidate its mechanism. METHODS Sprague-Dawley rats were divided into four groups: normal, normal + Hcy injection, TNBS model, and TNBS model + Hcy injection. Experimental colitis was induced by trinitrobenzene sulfonic acid (TNBS) in 50% ethanol; rats were injected subcutaneously with Hcy from the first day after the induction of experimental colitis on 30 consecutive days. To determine the severity of colitis, the disease activity index (DAI) was evaluated; colon tissues were collected for the detection of the activity of myeloperoxidase (MPO) and the contents of MDA, IL-1β, IL-6, TNF-α, MMP-2, and MMP-9. Intestinal epithelial permeability was assessed with Evans blue (EB) dye. The levels of Hcy in plasma and colon mucosa were measured by high-performance liquid chromatography-fluorescence detection (HPLC-FD). RESULTS Compared with the normal group, the DAI scoring and MPO activity, contents of MDA, IL-1β, IL-6, TNF-α, MMP-2, MMP-9 in the colon and EB in the small intestine were significantly increased in the TNBS group (P < 0.01). Compared with the TNBS model group, the DAI scoring, plasma and colonic mucosa Hcy levels, MPO activity and contents of MDA, IL-1β, IL-6, TNF-α, MMP-2, MMP-9 in colon and EB in small intestine were significantly increased in the TNBS-induced colitis rats with simultaneous Hcy injection (P < 0.01). CONCLUSION Hcy can increase intestinal permeability and aggravate inflammatory damage in rats with TNBS-induced colitis, the underlying mechanisms of which may be attributed to its effects of promoting the expression of MMP-2 and MMP-9, leading to injury of the intestinal barrier.