The induction of heme oxygenese-1 in intestinal mucosa of septic rat

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Backgrounds : Bilirubin is known to be a physiological antioxidant. Heme oxygenase (HO)-1, the rate-limiting enzyme in the heme degradation, is known to be induced by oxidative stress in the liver, kidney, or brain, but its induction has not yet been known in the intestine, We studied the expression of HO-1 in intestinal mucosa induced by oxidative stress using a rat septic model. Methods : Male Wistar rats were given with lipopolysaccharide (LPS) from E.coli (10mg/kg/body weight) by peritoneal injection. They were killed at 0, 1, 3, 5, 7.5, 10 and 24 hrs and their small intestinal mucosa was harvested. In intestinal mucosa, reduced glutathione (GSH), lipid peroxide, HO-1 mRNA, HO-1 protein, bilirubin, and bilirubin oxidative metabolites (BOM) were measured. Results : Intestinal GSH level was significantly decreased after 3 to 5 hrs by 40% of the control level. Lipid peroxides level was 1 .7-folds of control level at 5 hrs. The level of HO-1 mRNA increased to 3 times of the control at 3 hrs and HO-1 protein was strongly detected 7.5 hrs after LPS injection. Bilirubin level increased to 4-folds of control (peak level) at 10 hrs and BOM showed 5-folds increase with the peak level at 10 hrs. Conclusions : Sepsis reduced the GSH content and increased lipid peroxides. This intestinal oxidative stress induced the expression of HO-1 mRNA as well as the production of the protein in the intestinal mucosa. Bilirubin production and subsequent oxidation to BOM indicates that bilirubin acted as an antioxidant. This suggested that small intestine had ability to respond quickly to oxidative stress in sepsis, not just as a digestive and absorptive organ.