Protective role of heme oxygenase-1 on trinitrobenzene sulfonic acid-induced colitis in rats

Preliminary studies showed that the inducible form of heme oxygenase (HO-1) was induced and played a protective role in the process of inflammation. T he present study investigated the possible role of HO-1 in 2,4,6-trinitrobe nzene sulfonic acid (TNBS)-induced colitis in rats. We measured HO-1 activi ty in TNBS-induced colitis in rats and analyzed the severity of colitis alo ng with altered HO activity by assessing lesion area and myeloperoxidase ac tivity. HO-1 mRNA and protein expressions were determined at different time points after TNBS induction. Free radical production and inducible nitric oxide synthase (iNOS), which participate in oxidative injury, were also ass ayed. HO activity and HO-1 gene expression increased markedly after TNBS in duction. Administration with tin mesoporphyrin (SnMP), a HO inhibitor, pote ntiated the colonic damage along with a reduction in HO-1 activity. Further more, the reduction of HO-1 expression by SnMP also enhanced reactive oxyge n species and iNOS expression, both of which were dramatically increased af ter the TNBS enema. L-Arginine preteatment further aggravated the injurious action of SnMP. Our results indicate that HO-1 plays a protective role in the colonic damage induced by the TNBS enema, and the preventive effects pr obably result from decreased free radical production and inhibition of iNOS expression in colonic tissues.