Administration of bacterial lipopolysaccharide to rats induces heme oxygenase-l and formation of antioxidant bilirubin in the intestinal mucosa

Heme oxygenase (HO)-1, the rate-limiting enzyme in heme degradation, is ind uced by oxidative stress and its major end product, bilirubin, is a potent physiological antioxidant. We studied the induction of HO-1 and bilirubin p roduction in intestinal mucosa using a rat model of sepsis. E. coli lipopol ysaccharide was administered intraperitonealy to male Wistar rats and intes tinal mucosa was harvested. Intestinal lipid peroxides increased significan tly at 1 hy and peaked at 170% of the control value at 5 hr. GSH significan tly decreased at 3 hr, reaching the nadir of 50% of the control value at 5 hr. HO-1 mRNA was maximally induced fivefold at 3 hr and HO-1 protein maxim ally increased to 10 times the control value at 7.5 hr. Both bilirubin and bilirubin oxidative metabolites were maximally increased at 10 hr, to 4.3 a nd 3.7 times the control value, respectively. These data suggest that oxida tive stress in sepsis quickly induces HO-1 in intestinal mucosa and that su bsequent production of bilirubin works as an antioxidant. The small intesti nal mucose is an active participant in the general response to sepsis.