In vivo glycyrrhizin accelerates liver regeneration and rapidly lowers serum transaminase activities in 70% partially hepatectomized rats.
The in vivo effects of glycyrrhizin on restoration of liver mass and recovery of liver function were compared with those of epidermal growth factor (EGF), ibuprofen and dexamethasone in 70% partially hepatectomized rats. Hepatic regenerative activity was assessed based on the ratio of liver weight to 100 g body weight, and 5-bromo-2'-deoxyuridine (BrdU) incorporation into hepatocyte DNA in the remnant liver. Glycyrrhizin (50 mg/kg/day, i.p.)- or EGF (1.0 microg/kg/day, i.p.)-treated rats showed an approx. 1.4-fold increase in liver weight/100 g body weight ratio over saline-treated control rats on days 2 and 3 after 70% partial hepatectomy. BrdU labeling index in the remnant regenerating liver was significantly higher in glycyrrhizin- or EGF-treated rats when compared with saline-treated control rats on days 0.5 and 1. Ibuprofen (100 mg/kg/day, i.p.) and dexamethasone (0.1 mg/kg/day, i.p.) did not significantly increase either liver weight/100 g body weight ratio or BrdU labeling index. Serum activity of liver-related transaminases, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), elevated rapidly on day 1 and decreased to near pre-operative levels on day 5 after 70% partial hepatectomy in saline-treated control rats. Injection of glycyrrhizin or EGF significantly decreased the elevated serum ALT and AST activities on days 2 and 3 after hepatectomy when compared with saline-treated control rats. The transaminase-lowering effects of glycyrrhizin or EGF were smaller than those of ibuprofen and dexamethasone. These results demonstrate that injection of glycyrrhizin or EGF significantly enhances regeneration of liver mass and function, as well as recovery from the liver damage induced by surgical resection.
Kimura
Mitsutoshi
M
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, 1-1, Keyakidai, Sakado City, Saitama 350-0295, Japan.
Moro
Tadashi
T
Motegi
Hajime
H
Maruyama
Hiroyuki
H
Sekine
Mariko
M
Okamoto
Hiroshi
H
Inoue
Hideo
H
Sato
Toshitsugu
T
Ogihara
Masahiko
M
D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000187:drug effects / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000494:pharmacology; D019695:Glycyrrhizic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D006498:Hepatectomy; D007052:Ibuprofen / Q000008:administration & dosage / Q000494:pharmacology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D004815:Epidermal Growth Factor; D019695:Glycyrrhizic Acid; D003907:Dexamethasone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001973:Bromodeoxyuridine; D007052:Ibuprofen