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

Abstract

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.

Reduction of MDR1, MRP1 and BCRP expression in Crohn’s disease: a role in disease pathogenesis?

“…We have now found that the inflamed ileum of CD patients did not show the expected cytokine profile with elevated expression of IFN-g in the affected ileal tissue. However, we have found increased IFN-g expression in the treated group, which might have resulted from sulphasalazine treatment that can up-regulate the expression of IFN-g (39). Furthermore, there was no difference in IL-6 or IL1b expression among the defined groups, although IL-6 was borderline significantly elevated in the untreated group (p=0.0625).…”

Coadministration of ginger extract–Lactobacillus acidophilus (cobiotic) reduces gut inflammation and oxidative stress via downregulation of COX‐2, i‐NOS, and c‐Myc

“…Damage of intestinal barrier can aggravate mucosal inflammation, induce immune response, and is believed to be the key process responsible for infection‐ and immune factors‐initiated intestinal diseases including cancers (Bischoff et al, ). The proinflammatory cytokines, including TNF‐α and IL‐6, are known to disrupt tight junctions, decrease the transendothelial electrical resistance, and regulate the expression of intestinal mucosal barrier‐associated proteins, thereby increasing intestinal permeability (Ding et al, ). Significant reduction in serum TNF‐α level was observed on treatment with LAB ( p < .01), GE ( p < .001), and cobiotic ( p < .01).…”

Hyperhomocysteinemia Lead to Transmural Inflammation of Colon and Increase Severity of Disease in Acetic Acid-Induced Colitis in Rat

“…One of the possible mechanisms by which Hhcy is implicated in colon inflammation disease is the fact that it leads to endothelial dysfunction [43] which facilitate immune cells infiltration in colonic tissue by an increase of leukocyte adhesiveness and leukocyte diapedesis [44].…”