Effects of 4-aminosalicylic acid on migration, activation and apoptosis of polymorphonuclear neutrophil in rats with experimental colitis

Objective To investigate the effects of 4-aminosalicylic acid (4-ASA) on rats with 2,4,6-trinitrobenzenesulfonic acid-induced colitis in order to understand its mechanisms in treatment of inflammatory bowel disease (IBD). Methods Thirty SD rats were given 2,4,6-trinitrobenzenesulfonic acid to induce colitis and were divided into model group, 5-ASA (200 mg/kg) treated group and 4-ASA (200 mg/kg) treated group with 10 each. Another 10 rats were severed as normal control. Seven days later,all animals were sacraficed for estimation of colonic tissues. The iNOS and serum level of interleukin (IL)-8 were detected by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) ,respectively. And the apoptosis of polymorphonuclear neutrophil (PMN) was examined by flow cytometry. Results In comparison with model group, the body weight was increased in rats treated with 4-ASA (t= 14.09,P 0. 05). The expression of tissue iNOS was 73.55%±5.15% in model group, which was higher than that in control group [(5.95±1.45)% ,t=39.93,P<0.01)],but was lower than that in 5-ASA treated group [(37.80±3.82)%,t = 17.62,P<0.01] and 4-ASA treated group [(42.27±3.52) %, t= 15.76 ,P<0.01]. The serum level of IL-8 in model group was significantly higher than that in 5-ASA treated group and 4-ASA treated group (P<0. 01). The apoptosis of PMN in model group was lower than that in control group (t= 11.48,P<0.01), but higher than that in 5-ASA treated group (t= 7.51, P<0.01) and 4-ASA treated group (t= 10.47,P<0.01). Conclusions The efficacy of 4-ASA in treatment of IBD may be related to the mechanisms of reducing the migration and the activities of PMN, up-regulating PMN apoptosis and scavenging reactive oxygen radicals produced by PMN. Key words: Inflammatory bowel disease; p-aminosalicylic acid; Interleukin-8; Apoptosis