Liver, Pancreas, and Biliary TractCarbon monoxide from heme catabolism protects against hepatobiliary dysfunction in endotoxin-treated rat liver☆,☆☆
Section snippets
Preparation of perfused rat livers
Male Wistar rats (260–280 g) were obtained from Nippon Biosupp. Center, Inc. (Tokyo, Japan). All animals were allowed free access to laboratory chow and tap water. Protocols for the current experiments were approved by the Institutional Guidelines for Animal Care and Experiments in Keio University School of Medicine. Rats were anesthetized intraperitoneally with pentobarbital sodium (50 mg/kg). When necessary, rats were pretreated with intraperitoneal injection of lipopolysaccharide (LPS;
LPS induces overproduction of NO and CO in the liver
Figure 1 illustrates an induction of iNOS and HO-1 and overproduction of their products NO and CO in LPS-pretreated livers.
Discussion
Liver is a major organ that helps detoxification of free heme molecules and biliary excretion of their metabolites such as bilirubin and requires self-protective mechanisms for tolerance against the heme toxicity. Impairment of such mechanisms could jeopardize liver homeostasis, and thus lead to a risk of the organ dysfunction. The present study provided evidence that endotoxemic liver could greatly expand its ability to decompose Hb-derived heme through an induction of HO-1 in hepatocytes and
Acknowledgements
The authors thank Dr Ken-ichiro Hirano and Hitomi Irisawa for technical supports.
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Supported by grants from Tokyo Biochemical Research Foundation and from Advanced Medical Technology in Health Sciences Research Grants from Ministry of Health and Welfare in Japan.
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Address requests for reprints to: Makoto Suematsu, M.D., Ph.D., Associate Professor, Department of Biochemistry, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. e-mail: [email protected]; fax: (81) 3-3358-8138.