Intervention of 3-aminobenzamide against Dextran Sulphate Sodium induced colitis in mice: Investigations on molecular mechanisms.

Various preclinical and clinical studies reported that Poly [ADP-ribose] polymerase 1 plays significant role in all acute and chronic inflammatory diseases with different etiopathogenesis. The present study aims to investigate the protective effect of 3-aminobenzamide in Dextran Sulphate Sodium induced ulcerative colitis and associated molecular mechanisms. Ulcerative colitis in male BALB/c mice was induced using Dextran sulphate sodium (3 %w/v) for 3 cycles with 7 days recovery period in-between. 3-aminobenzamide was administered at the doses of 5, 10 and 20 mg/kg starting from the I week of remission period and was continued till the termination of the experiment. The effect of 3-aminbenzamide was evaluated using biochemical parameters, histopathological evaluations, ELISA, immunohistochemistry, immunofluorescence and Western blot analysis. All the doses of 3-aminobenzamide (5 mg/kg; 10 mg/kg and 20 mg/kg) ameliorated the severity of ulcerative colitis by modulating various molecular targets such as poly[ADP-ribose] polymerase 1, nuclear factor kappa-light-chain-enhancer of activated B cells, NLR family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, cysteine aspartases, interleukin-1β, proliferating cell nuclear antigen, sirtuin 1, adenosine monophosphate-activated protein kinase, tumour necrosis factor-α and catalase. However, the lower doses (5 and 10 mg/kg) exerted more prominent effects in comparison to the high dose (20 mg/kg). Further, 3-aminobenzamide treatment restored the intestinal integrity by increasing the expression of occludin and significantly ameliorated ulcerative colitis associated elevated lipopolysaccharides, oxidative and nitrosative stress, cellular damage and apoptosis. Lower doses of 3-aminobenzamide showed more prominent protective effects against ulcerative colitis associated damage as compared to higher dose.