The effects of 10 triterpenoid compounds on experimental liver injury in mice.
The purpose of this study was to compare the hepatoprotective effects of 10 oleanane-type triterpenoid compounds on three known hepatotoxicants in mice. These compounds include oleanolic acid, ursolic acid, uvaol, alpha-hederin (alpha-H), hederagenin, glycyrrhizin, 18 alpha-glycyrrhetinic acid (alpha-GA), 18 beta-glycyrrhetinic acid (beta-GA), 19 alpha-hydroxyl asiatic acid 28-O-beta-D-glucoside (HAG), and 19 alpha-hydroxyl asiatic acid (HA). They were administrated sc for 3 days at 200 mumol/kg, except for alpha-H, which was given at 100 mumol/kg for 2 days. Acute liver injury was produced in male CF-1 mice by CCl4 (15 microliters/kg, ip), acetaminophen (500 mg/kg, ip), and cadmium chloride (3.7 mg/kg, iv). Liver damage was assessed by serum activities of alanine aminotransferase and sorbitol dehydrogenase, as well as by histopathological examination. alpha-Hederin, ursolic acid, and oleanolic acid markedly decreased the toxicity produced by all three hepatotoxicants. Uvaol significantly decreased CCl4- and Cd-induced hepatotoxicity, but had no effect on acetaminophen toxicity. Glycyrrhizin, alpha-GA, and beta-GA decreased acetaminophen-induced liver injury, whereas hederagenin, HAG, and HA did not protect against any of the hepatotoxicants. In addition, alpha-hederin, ursolic acid, oleanolic acid, and uvaol increased hepatic metallothionein levels by 87-, 48-, 28-, and 10-fold, respectively, as determined by the Cd/hemoglobin assay. In conclusion, among the 10 triterpenoid compounds examined, alpha-hederin, ursolic acid, and oleanolic acid appear to be the most effective in protecting against CCl4-, acetaminophen-, and Cd-induced liver injury.
Liu
J
J
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417.
Liu
Y
Y
Mao
Q
Q
Klaassen
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CD
D000410:Alanine Transaminase / Q000187:drug effects; D000818:Animals; D007064:L-Iditol 2-Dehydrogenase / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008668:Metallothionein / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
D014315:Triterpenes; D008668:Metallothionein; D007064:L-Iditol 2-Dehydrogenase; D000410:Alanine Transaminase