The Acute Toxicity of 1,2,4-Trichlorobenzene in Sprague-Dawley Rats Depleted of Glutathione by Treatment with Buthionine Sulfoximine

BSO 유도 글루타치온 저감 흰쥐에서 1,2,4-trichlorobenzene의 급성독성

  • 안영수 (국립환경연구원 환경보건연구부)
  • Published : 1996.06.01

Abstract

1,2,4-trichlorobenzene (1,2,4-TCB) is used as a dye carrier, an intermediate in the syn[hesis of herbicides, aflame retardant, and for other purpose. After a single oral administration of 1,2,4-TCB (200 mg/kg, 400 mg/kg) in rats, toxic effects were studied by means of serum biochemical and hematological analysis, and liver calcium concentration. Administration of 1,2,4-TCB resulted in dose-dependent manner liver and kidney damage being suggested by increased serum alanine aminbtransferase (ALT) activities, liver calcium concentration and blood urea nitrogen (BUN). Pretreatment with DL-buthionine sulfoximine (BSO, 2 mmol/kg, i.p.) considerably decreased liver glatathione concentration, which was accompanied by markedly elevated serum ALT activites. It is well-known that toxicity of halogenated benzene such as bromobenzene, 1,4-dichlorobenzene is increased by pretreatment of phenobarbital, and protected by pretreatment of cytochrorn P450 inhibitor including metyrapone. However, there were no obvious alterations in toxicity of 1,2,4-TCB by pretreatment of phenobarbital or metyrapone. In comparison with control group, treatment groups exhibited significant changes in some parameters of hematological analysis but all hematological values remained within normal ranges.

Keywords

References

  1. Investigation of selected potential environmental contaminants; Halogenated benzenes, EPA 560/2-77-004 Anon
  2. Ambient water quality criteria for chlorinated benzenes; EPA 440/5-80-028 Anon
  3. Ann. Occup. Hjg. v.12 The acute toxicity and skin irritant properties of 1,2,4-trichlorobenzene Brown,V.K.H.;Muir,C.;Thorpe,E.
  4. Biochem. Pharmacol v.36 Lipid peroxidation, protein thiols and calcium homeostasis in bromobenzene-induced liver damage Casini,A.F.;Maellaro,E.;Pompella,A.;Fellari,M.;Comporti,M.
  5. Toxicol. Appl. Pharmacol v.111 The liver, kidney, and thyroid toxicity of chlorinated benzenes Den Besten,C.;Vet,J.J.R.M.;Besselink,H.T.;Kiel,G.S.;Berkel,B.J.M.;Beems,R.;van Bladeren,P.J.
  6. Toxicol. Appl. Pharmacol v.45 Cocaine-induced hepatotoxicity in mice Evans,M.A.;Harbison,R.D.
  7. Life Sci v.29 The role of calcium in cell death Farber,J.L.
  8. J. Water Pollut. Control Fed. v.48 Carpet and rug industry case study I: Water and waste water treatment plant operation Gaffney,P.E.
  9. Pharmacology v.11 Bromobenzene-induced liver necrosis: Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite Jollow,D.J.;Mitchell,J.R.;Zampaglione,N.;Gillette,J.R.
  10. Drug Metab. Dispos v.12 Multiple reactive metabolites derived from bromobenzene Lau,S.S.;Monks,T.J.;Gillette,J.R.
  11. J. Pharmacol. Exp. Ther v.214 Metabolic activations and detoxification of bromobenzene leading to cytotoxicity Lau,S.S.;Abrams,G.D.;Zannoni,V.G.
  12. Functions of Glutathione in Liver and Kidney Meister,A.;H.Sies(ed.);A.Wendel(ed.)
  13. J. Pharmacol. Exp. Ther. v.187 Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione Mitchell,J.R.;Jollow,D.J.;Potter,W.Z.;Gillette,J.R.;Brodie,B.B.
  14. Toxicology v.94 p-Dichlorobenzene-induced hepatotoxicity in mice depleted of glutathione by treatment with buthionine sulfoximine Mizutani,T.;Nakahori,Y.;Yamamoto,K.
  15. Drug Chem. Toxicol. v.5 Subchronic dermal toxicity study of trichlorobenzene in the rabbit Rao,K.S.;Johnson,K.A.;Henck,J.W.
  16. Biochem. Pharmacol. v.12 Experimental porphyria in rats induced by chlorinated benzenes Rimington,C.;Ziegler,G.
  17. Anal. Biochem. v.25 Estimation of total, protein-bound, and non-protein sulfhydryl groups in tissue with Ellman's reagent Sedlak,J.;Lidsay,R.H.
  18. Toxic Interactions The role of glutathione in protection against chemically induced cell injury Smith,P.F.;Rush,G.F.;R.S.Goldstein(ed.);W.R.Hewitt(ed.);J.B.Hook(ed.)
  19. Toxicol. Appl. Pharmacol v.109 The acute hepatotoxicity of the isomers of dichlorobenzene in Fischer-344 and Sprague-Dawley rats: Isomer-specific and strain-specific differential toxicity Stine,E.R.;Gunawardhana,L.;Sipes,I.G.
  20. Toxicol. Appl. Pharmacol v.100 The relation between the oxidative biotransformation of hexachlorobenzene and its porphyrinogenic activity Van Ommen,B.;Hendriks,W.;Bessems,J.G.M.;Geesink,G.;Muller,F.;van Bladeren,P.J.
  21. Pestic. Monit. J. v.13 Polychlorinated biphenyls and other organic chemical residues in fish from major watersheds of the U.S. Veith,G.D.;Kuehl,D.W.;Leonard,E.N.;Publishi,F.A.;Gray,L.E.
  22. Enviromental health criteria 128; Chlorobenzenes other than hexachlorobenzene WHO
  23. Acta bio. Cracoviensia v.21 Reactivity of the white blood cell system to toxic action benzene and its derivatives Zub,M.