Miyazaki M, Kato M, Tanaka M, Tanaka K, Takao S, Kohjima M, Ito T, Enjoji M, Nakamuta M, Kotoh K, Takayanagi R. Antithrombin III injection via the portal vein suppresses liver damage. World J Gastroenterol 2012; 18(16): 1884-1891 [PMID: 22563168 DOI: 10.3748/wjg.v18.i16.1884]
Corresponding Author of This Article
Masayuki Miyazaki, MD, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. mmasayuk@intmed3.med.kyushu-u.ac.jp
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Original Article
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Masayuki Miyazaki, Masaki Kato, Masatake Tanaka, Kosuke Tanaka, Shinichiro Takao, Motoyuki Kohjima, Tetsuhide Ito, Munechika Enjoji, Makoto Nakamuta, Kazuhiro Kotoh, Ryoichi Takayanagi, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Motoyuki Kohjima, Makoto Nakamuta, Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka 810-0065, Japan
Munechika Enjoji, Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan
Author contributions: Miyazaki M and Kato M performed the majority of experiments and wrote the paper; Tanaka M, Tanaka K, Takao S and Kohjima M supported the experiments; Ito T, Enjoji M, Nakamuta M and Kotoh K analyzed the data; Takayanagi R supervised writing of the paper.
Correspondence to: Masayuki Miyazaki, MD, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. mmasayuk@intmed3.med.kyushu-u.ac.jp
Telephone: +81-92-6425282 Fax: +81-92-6425287
Received: August 3, 2011 Revised: December 20, 2011 Accepted: December 31, 2011 Published online: April 28, 2012
Abstract
AIM: To investigate the effects of antithrombin III (AT III) injection via the portal vein in acute liver failure.
METHODS: Thirty rats were intraperitoneally challenged with lipopolysaccharide (LPS) and D-galactosamine (GalN) and divided into three groups: a control group; a group injected with AT III via the tail vein; and a group injected with AT III via the portal vein. AT III (50 U/kg body weight) was administrated 1 h after challenge with LPS and GalN. Serum levels of inflammatory cytokines and fibrin degradation products, hepatic fibrin deposition, and hepatic mRNA expression of hypoxia-related genes were analyzed.
RESULTS: Serum levels of alanine aminotransferase, tumor necrosis factor-α and interleukin-6 decreased significantly following portal vein AT III injection compared with tail vein injection, and control rats. Portal vein AT III injection reduced liver cell destruction and decreased hepatic fibrin deposition. This treatment also significantly reduced hepatic mRNA expression of lactate dehydrogenase and heme oxygenase-1.
CONCLUSION: A clinically acceptable dose of AT III injection into the portal vein suppressed liver damage, probably through its enhanced anticoagulant and anti-inflammatory activities.
