Effect of Biphenyl Dimethyl Dicarboxylate on Chemical-Induced Hepatotoxicity

  • 발행 : 1995.12.01

초록

To know the mechanism of biphenyl dimethyl dicarboxylate (DDB) in the protection of chemically induced hepatotoxicity, the activity of glutamic pyruvic tran.saminase (GPT) and the level of lipid peroxidation metabolite (malondialdehyde, MDA) and ATP content in hepatocytes were determined in serum and primarily cultured hepatocytes. For in vibo study, rats were pretreated with DDB (300 mg/ kg, p.o.)for 7 days. DDB pretreatment efficiently reduced the elevation of serum GPT activity induced by carbon tetrachloride (1.6 ml/kg, s.c.) and acetaminophen administration (1500 mg/kg, i.p.). In ex vivo study, hepatocytes were isolated from the rats pretreated with DDB (300 mg/kg, p.o.)for 7 days and cultured for 12 hrs before inducing cytotoxicity with chemicals. The MDA formation and the GPT release induced by adriamycin $(1\times10^{-4} mg/ml)$ and cisplatin $(2\times10^{-4} mg/ml)$ were markedly decreased in the hepatocytes from the rats pretreated with DDB as compared to vehicle only. However, DDB pretreatment did not prevent the decrease of ATP contents of hepatocytes induced by cisplatin and adriamycin. In in vitro experiment, DDB was pretreated in primary cultured hepatocytes for 3 days. DDB enhanced the decreases of ATP contents induced by cisplatin and adriamycln. These results suggest that DDB may protect the hepatocytes from injury induced by hepatotoxlcants through inhibiting the lipid peroxidation.

키워드

참고문헌

  1. Toxicology v.95 no.1 Adriamycin-induced hepatic and myocardial lipid peroxidation and DNA damage, and enhanced excretion of urinary lipid metabolites in rats Bagchi,D.:bagchi,M.;Hassoun,E.A.;Kelly,J.;Stohs,S.J.
  2. Physiol. Rev. v.59 Hydroperoxide metabolism in mammalian organs Chance,B.;Sies,H.;Boveris,A.
  3. Acta Pharmaceutica Sinca v.24 no.1 The effect of biphenyldimethyl dicarboxylate (DDB) on the fluidity of human erythrocyte membrane Chen,L.;Chen,W.W.
  4. Anal. Biochem. v.179 Viability measurements in mammalian cell systems Cook,J.A.;Mitchell,J.B.
  5. Chin. Med. J. v.70 no.4 Protective effects of biphenyldimethyl dicarboxylate on damage in isolated rat hepatocytes induced by carbon tetrachloride and D-galactosamine Fu,T.;Liu,G.
  6. J. Appl. Biochem. v.3 ATP determination with firefly luciferase Leach,F.R.
  7. Kor. J. Intern. Med. v.40 no.2 Prospective, randomized, controlled trial with diphenyl-dimethyl-dicarboxylate in chronic active liver diseases: The effect on lowering serum alanine aminotransferase levels Lee,H.S.;Kim,Y.T.;Jung,H.C.;Yoon,Y.B.;Song,I.N.;Kim,C.Y.
  8. Memorias do Instituto Oswaldo Cruz v.86 Bioactivity of neolignans from fructus Schizandrae Li,X.Y.
  9. Chemic-Biol. Interactions v.39 no.3 Pharmacological properties of dibenzo[a,c] cyclooctene derivatives isolated from Fructus Schizandrae chinensis II. Induction of phenobarbital like hepatic monooxygenases Liu,K.T.;Cresteil,T.;Columelli,S.;Leaca,P.
  10. Chemic-Biol. Interactioins v.41 no.1 Pharmacological properties of Dibenzo[a,c]cyclooctene derivatives isolated from Fructus Schizandrae Chinensis III. Inhibitory effects on carbon tetrachloride-induced lipid peroxidation, metabolism and covalent binding of carbon tetrachloride to lipids Liu,K.T.;Lesca,P.
  11. J. Ethnopharmacol. v.42 no.3 The effect of chinese hepatoprotective medicines on experimental liver injury in mice Liu,J.;Liu,Y.;Klaassen,C.D.
  12. Anal. Biochem. v.95 Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction Ohkawa,H.;Ohishi,N.;Yagi,K.
  13. Methods cell Biol. v.13 Preparation of isolated rat liver cells Seglen,P.O.
  14. Kor. J. Pharmacol. v.30 no.2 Effects of biphenyldimethyl dicarboxylate (DDB) on the lipid peroxidation, oxygen free radical scavenging enzyme activities and hepatic functions in ethanol-induced hepatotoxic rats. Song,H.Y.;Ha,K.R.;Koh,H.C.;Shin,I.C.;Suh,T.K.
  15. Eur. J. Pharmacol. v.248 no.2 Involvement of free radicals in cisplatin-induced emesis in Suncus murinus Torii,Y.;Mutoh,M.;Saito,H.;matuki,N.
  16. Biochem. Pharmacol. v.46 no.6 Preventive effect of gomisin A, a lignan component of shizandra fruits, on acetaminophen-induced hepatotoxicity in rats Yamada,S.;Murawaki,Y.;Kawasaki,H.