title: Glycyrrhizin prevents liver injury by inhibition of high-mobility group box 1 production by Kupffer cells after ischemia-reperfusion in rats.
abstract: High-mobility group box 1 (HMGB1) acts as an early mediator of inflammation and organ damage in hepatic ischemia-reperfusion (I/R) injury. Glycyrrhizin is a natural anti-inflammatory and antiviral triterpene in clinical use. The purpose of this study was to investigate the effect of glycyrrhizin on liver injury caused by I/R and production of HMGB1 by Kupffer cells in rats. In the first test period, rats were given saline or glycyrrhizin 20 min before segmental hepatic warm I/R. Serum alanine aminotransferase and HMGB1 levels and hepatic histopathological findings were evaluated after I/R. Furthermore, expression of HMGB1 in the liver was assessed by immunohistochemical staining after I/R. Kupffer cells were isolated by collagenase digestion and differential centrifugation, and production of HMGB1 was assessed. In another set of experiments, the effect of inhibition of Kupffer cells by injection of liposome-entrapped dichloromethylene diphosphonate (lipo-MDP) on liver injury and expression of HMGB1 were investigated after I/R. Liver injury was prevented in the glycyrrhizin group compared with the control group. Furthermore, serum HMGB1 levels were also significantly blunted in the glycyrrhizin group compared with the control group. Cells expressing HMGB1 were detected in the hepatic sinusoid by immunohistochemistry and recognized morphologically as Kupffer cells. Furthermore, the expression of HMGB1 was reduced in the glycyrrhizin group compared with the control group. Production of HMGB1 was reduced in Kupffer cells isolated from the glycyrrhizin group compared with the control group. It is noteworthy that treatment with lipo-MDP significantly blunted serum HMGB1 levels and prevented liver injury after I/R. These results suggest that glycyrrhizin has the therapeutic potential to prevent warm I/R-induced injury during hepato-biliary surgery.
authors: First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors: Masahito
authors: M
authors: Ogiku
authors: Hiroshi
authors: H
authors: Kono
authors: Michio
authors: M
authors: Hara
authors: Masato
authors: M
authors: Tsuchiya
authors: Hideki
authors: H
authors: Fujii
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control; D004002:Clodronic Acid / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D008081:Liposomes; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D024243:HMGB1 Protein; D008081:Liposomes; D004002:Clodronic Acid; D019695:Glycyrrhizic Acid; D000410:Alanine Transaminase