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Administration of Bacterial Lipopolysaccharide to Rats Induces Heme Oxygenase-1 and Formation of Antioxidant Bilirubin in the Intestinal Mucosa

Overview
Journal Dig Dis Sci
Specialty Gastroenterology
Date 2001 Mar 22
PMID 11258550
Citations 6
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Abstract

Heme oxygenase (HO)-1, the rate-limiting enzyme in heme degradation, is induced by oxidative stress and its major end product, bilirubin, is a potent physiological antioxidant. We studied the induction of HO-1 and bilirubin production in intestinal mucosa using a rat model of sepsis. E. coli lipopolysaccharide was administered intraperitonealy to male Wistar rats and intestinal mucosa was harvested. Intestinal lipid peroxides increased significantly at 1 hr and peaked at 170% of the control value at 5 hr. GSH significantly 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 maximally 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 and 3.7 times the control value, respectively. These data suggest that oxidative stress in sepsis quickly induces HO-1 in intestinal mucosa and that subsequent production of bilirubin works as an antioxidant. The small intestinal mucosa is an active participant in the general response to sepsis.

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References
1.
Willis D, Moore A, Frederick R, Willoughby D . Heme oxygenase: a novel target for the modulation of the inflammatory response. Nat Med. 1996; 2(1):87-90. DOI: 10.1038/nm0196-87. View

2.
Ossola J, Groppa M, Tomaro M . Relationship between oxidative stress and heme oxygenase induction by copper sulfate. Arch Biochem Biophys. 1997; 337(2):332-7. DOI: 10.1006/abbi.1996.9788. View

3.
Pritts T, Moon R, Fischer J, Salzman A, Hasselgren P . Nuclear factor-kappaB is activated in intestinal mucosa during endotoxemia. Arch Surg. 1998; 133(12):1311-5. DOI: 10.1001/archsurg.133.12.1311. View

4.
Shimizu S, Izumi Y, Yamazaki M, Shimizu K, Yamaguchi T, Nakajima H . Anti-bilirubin monoclonal antibody. I. Preparation and properties of monoclonal antibodies to covalently coupled bilirubin-albumin. Biochim Biophys Acta. 1988; 967(2):255-60. DOI: 10.1016/0304-4165(88)90017-7. View

5.
Rosenberg D, Kappas A . Induction of heme oxygenase in the small intestinal epithelium: a response to oral cadmium exposure. Toxicology. 1991; 67(2):199-210. DOI: 10.1016/0300-483x(91)90143-o. View