Treatment with Mesna and n‐3 polyunsaturated fatty acids ameliorates experimental ulcerative colitis in rats

Abstract

Oxidative damage is a central feature of ulcerative colitis. Here, we tested whether the antioxidant Mesna, when administered alone or in combination with n-3 polyunsaturated fatty acids (n-3 PUFAs), affects the outcome of dextran sodium sulphate (DSS)-induced ulcerative colitis in rats. After the induction of colitis, DSS-treated rats were further treated orally (p.o), intraperitoneally (i.p) or intrarectally (i.r) for either 7 or 14 days with Mesna, n-3 PUFAs or both. Rats were euthanized at the end of each treatment period. Clinical disease activity index was recorded throughout the experiment. At necropsy colorectal gross lesions were scored. Colitis was scored histologically, and the expression of myeloperoxidase (MPO), caspase-3, inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF-κΒ) in colonic tissue was assessed by immunohistochemistry. Mesna alone was sufficient to significantly reduce colorectal tissue damage when administered orally or intraperitoneally. Orally coadministered n-3 PUFAs enhanced this effect, resulting in the significant suppression of DSS colitis after 7 days, and a remarkable recovery of colorectal mucosa was evident after 14 days of treatment. The amelioration of colon pathology co-existed with a significant decrease in MPO expression, overexpression of iNOS and reduction of nuclear NF-κB p65 in inflammatory cells, and the suppression of apoptosis in colonic epithelial cells. The simultaneous administration of Mesna and n-3 PUFAs is particularly effective in ameliorating DSS colitis in rats, by reducing oxidative stress, inflammation and apoptosis, probably through a mechanism that involves the inhibition of NF-κB and overexpression of iNOS.

Effect of <i>Eucommia ulmoides</i> Leaf Extract on Chronic Dextran Sodium Sulfate-Induced Colitis in Mice

“…Cell death and up-regulated caspase 3-positive cells in the intestinal mucosa has also been reported to be involved in the development of DSS-induced colitis. [18][19][20] ELE has been shown to suppress H 2 O 2 -induced rat osteoblastic MC3T3-E1 cell apoptosis by inhibiting the expression of caspases 3, 6, 7, and 9. 21) Therefore, it is likely that ELE administration may suppress cell death of intestinal mucosal cells as a potential mechanism for its anti-colitis effect.…”

Periplaneta americana extract promotes intestinal mucosa repair of ulcerative colitis in rat

“…Myeloperoxidase is a 140-kDa heme protein secreted primarily by neutrophils and stored in eosinophils 38 , 39 . Colonic injury leads to the activation of neutrophils and macrophages, and the release of MPO from activated neutrophils causes hydrogen peroxide (H 2 O 2 ) to produce hypochlorous acid (HOCl) and chlorine anions (Cl − ) to further damage the colon 40 .…”

Mesna (2-mercaptoethane sodium sulfonate) functions as a regulator of myeloperoxidase

“…In a similar mechanism, mesna protects kidney tissue against ischemia/reperfusion injury induced by oxidative damage [51]. It has also shown that mesna significantly reduces colorectal tissue damage when administered orally or intraperitoneally by reducing oxidative stress, inflammation and apoptosis, likely through a mechanism that involves the inhibition of NF-κB and overexpression of iNOS [30]. Consistent with these results, we show that mesna is a potent inhibitor of MPO with an IC 50 of 5 μM.…”