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 alkaloi ds (PAs), and often cause acute and chronic liver damages in man. Liquorice , a known antihepatitis, is commonly used with PA-containing herbs concurre ntly, and hepatotoxicity induced by such combined uses was not pronounced. The present study is to investigate effects of glycyrrhizin (GL) and 18 bet a-glycyrrhetinic acid (CA), the major biologically active ingredients of li quorice, against PA-induced hepatotoxicity in rats. Single dose (35 mg/kg, i.p.) of retrorsine (RET), a typical potent hepatoto xic PA, was given to rats to induce liver injury. A single dose pretreatmen t 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.) o r GA (10 mg/kg/day, i.p.) for three consecutive days prior to retrorsine ex posure, the elevated serum GOT and GPT levels induced by retrorsine were si gnificantly reduced. Serum levels of transaminases almost returned to norma l (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 hepatocell ular damages were observed. The results demonstrated that a three-day pretr eatment with either GL or GA exhibited protective effect on retrorsine-indu ced liver damage in rats. (C) 1999 Elsevier Science Ltd,All rights reserved .