The effects of pretreatment with glycyrrhizin and glycyrrhetinic acid on the retrorsine-induced hepatotoxicity in rats.
A wide variety of medicinal herbs contain hepatotoxic pyrrolizidine alkaloids (PAs), and often cause acute and chronic liver damages in man. Liquorice, a known antihepatitis, is commonly used with PA-containing herbs concurrently, and hepatotoxicity induced by such combined uses was not pronounced. The present study is to investigate effects of glycyrrhizin (GL) and 18beta-glycyrrhetinic acid (GA), the major biologically active ingredients of liquorice, against PA-induced hepatotoxicity in rats. Single dose (35 mg/kg, i.p.) of retrorsine (RET), a typical potent hepatotoxic PA, was given to rats to induce liver injury. A single dose pretreatment with GL or GA prior to retrorsine challenge did not show hepatoprotection. However, when rats were pretreated with either GL (200 mg/kg/day, i.p.) or GA (10 mg/kg/day, i.p.) for three consecutive days prior to retrorsine exposure, the elevated serum GOT and GPT levels induced by retrorsine were significantly reduced. Serum levels of transaminases almost returned to normal (GOT: 56+/-2 (control), 104+/-5 (RET), 64+/-3 (GL + RET) and 59+/-3 (GA + RET). GPT: 40+/-2 (control), 90+/-7 (RET), 45+/-2 (GL + RET) and 45+/-4 (GA + RET) SF units/ml). Furthermore, no extensive hepatocellular damages were observed. The results demonstrated that a three-day pretreatment with either GL or GA exhibited protective effect on retrorsine-induced liver damage in rats.
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT. linge@cuhk.edu.hk
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D000287:Administration, Topical; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury; D004334:Drug Administration Schedule; D005978:Glutathione / Q000032:analysis; D006034:Glycyrrhetinic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D019695:Glycyrrhizic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000972:Antineoplastic Agents, Phytogenic; D011763:Pyrrolizidine Alkaloids; D019695:Glycyrrhizic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D006034:Glycyrrhetinic Acid; C003300:retrorsine