Effect of Cyclohexane Treatment on the Liver Damage in CCl4-Pretreated Rats

CCl4전처치한 흰쥐에 Cyclohexane 투여가 간손상에 미치는 영향

  • 윤종국 (계명대학교 공중보건학과) ;
  • 김현희 (계명대학교 공중보건학과)
  • Published : 2003.06.01

Abstract

TO evaluate an effect of cyclohexane treatment on the degree of liver damage, rats were induced liver damage with 10 or 17 times $CCl_4$ injection (0.1 m1/100 g body wt., 50% $CCl_4$ dis-solved in olive oil) at intervals of every other day. Cyclohexane (1.56 g/kg body wt., i.p.) was administrated to the animals at 48 hours after the last pretreatment of $CCl_4$ . Rats were sacrificed at 4 hours after injection of cyclohexane. On the basis of histopathological findings, liver weight/body weight (LW/ BW, %), activities of serum alanine aminotransferase (ALT), xanthine oxidase (XO) and akaline phosphatase (ALP), and contents of liver protein and manlondialdehyde (MDA), $CCl_4$ -pretreatment induced liver damage. And $CCl_4$ 17 times treated group showed more severe liver damage than $CCl_4$ 10 times treated group. Administration of one dose of cyclohexane to $CCl_4$ 10 times treated animals resulted in the enhanced liver damage; liver necrosis with proliferation of fibroblast and bile duct abnormality, and increase in hepatic MDA content and the activities of serum ALP and ALT, But the enhanced liver damage was not found in $CCl_4$ 17 times treated animals. Serum cyclohexanone concentrations at 4 or 8 hours after injection of cyclohexane were higher in all liver damaged groups than normal group and were somewhat higher In $CCl_4$ 17 times treated animals than $CCl_4$ 10 times treated ones. Among the oxygen free radical metabolizing enzymes, hepatic cytochrome P45O dependent aniline hydroxylase (CYPdAH) activity in cyclohexane metabolizing enzyme system was meaningfully increased by the injection of cyclohexane to the liver damaged rats, with increased Vmax and high affinity to aniline. LW/BW (%) and activities of serum XO and ALT were more significantly increased in liver damaged groups than normal group by administration of cyclohexanone. In conclusion, it is assumed that an enhancement of liver damage by injection of one dose of cyclohexane to liver damaged animals might be caused by oxygen free radicals and cyclohexanone.

Keywords

References

  1. Catalase v.2 Methods of Enzymatic Analysis Aebi,H.
  2. J. Chromatogr. B Biomed. Sci. Appl. v.696 Simultaneous determination of cyclohexene oxide and its metabolites in rat plasma and urine by gas chromatography Bao,J.;Smith,R.L.;Sauer,J.M.;Pillai,U.;Sipes,I.G. https://doi.org/10.1016/S0378-4347(97)00232-6
  3. Toxicol. Left. v.45 Evaluation of the subacute nephrotoxicity of cyclohexane and other indusrtial solvents in the female Sprague-Dawley rat Bernard,A.M.;de Russis,R.;Normand,J.C.;Lauwerys,R.R. https://doi.org/10.1016/0378-4274(89)90018-0
  4. J. Biol. Chem. v.164 A method for the rapid determination of alkaline phosphatase with five cubic milimeters of serum Bassey.O.A.;Lowry,O.H.
  5. Biochem. Pharmacol. v.31 Multiple drug metabolism: p-nitroanisole reversal of acetone enhanced aniline hydroxylation Bidlack,W.R.;Lowery,G.L. https://doi.org/10.1016/0006-2952(82)90176-9
  6. New Engl. J. Med. v.303 Normobaric oxygen toxicity of the lung Deneke,S.M.;Fanburg,B.L. https://doi.org/10.1056/NEJM198007103030204
  7. Biochem. J. v.72 Studies in detoxication.The metabolism of cyclo[${ }^{14}C$]hexane and its derivatives Elliott,T.H.;Parke,D.V.;Williams,R.T. https://doi.org/10.1042/bj0720193
  8. Arch. Biochem. Biophys. v.82 Tissue sulfhydryl group Ellman,G.L. https://doi.org/10.1016/0003-9861(59)90090-6
  9. Lab. Invest. v.47 Biology of disease: free radicals and tissue injury Freeman,B.A.;Crapo,J.D.
  10. J. Biol. Chem. v.249 Glutathione S-transferase. The first enzymatic step in mercapturic acid and formation Habig,W.H.;Pabst,M.J.;Jakoby,W.B.
  11. Pharmacol. Ther. v.40 Drugmetabolism in liver disease Howden,C.W.;Birnie,G.G.;Brodie,M.J. https://doi.org/10.1016/0163-7258(89)90088-0
  12. Ind. Health v.36 Evaluation of organic solventinduced inflammation modulated by neuropeptides in the abdominal skin of hairless rats Iyadomi,M.;Higaki,Y.;Ichiba,M.;Morimoto,M.;Tomokuni,K. https://doi.org/10.2486/indhealth.36.40
  13. Xenobiotica v.1 The metabolism of alicyclic ketones in the rabbit and rat James,S.P.;Waring.R.H. https://doi.org/10.3109/00498257109112268
  14. Gastroenterol v.62 Alkaline phosphatase Kaplan,M.M.
  15. J. Clin. Invest. v.34 A note on the spectrophotometer assay of glutamic oxalacetic transaminase in human blood serum Karmen,A.
  16. J. Gerontol. v.35 Aspects of free radical reaction in biological systems: aging Leibovitz,B.E.;Siegel,B.V. https://doi.org/10.1093/geronj/35.1.45
  17. Ehtel Browning's toxicity and metabolism of industrial solvents Cyclohexance Longacre,S.L.;R.Snyder.(ed.)
  18. J. Biol. Chem. v.193 Protein measurement with the folin phenol reagent Lowry,O.H.;Rosebrough,N.J.;Farr,A.L.;Randall,R.J.
  19. Arch. Biochem. Biophys. v.255 Negative and positive assays of superoxide dismutase based on hematoxylin autoxidation Martin,J.P.Jr.;Dailey,M.;Sugarman,E. https://doi.org/10.1016/0003-9861(87)90400-0
  20. Neuro-toxicol. v.15 Astrocytes as targets for CNS effects of organic solvents in vitro Naskali,L.;Oksanen,H.;Tahti,H.
  21. NIOSH pocket guide to chemical hazards National Institute for Occupational Safety and Health(NIOSH)
  22. Arch. Biochem. Biophys. v.180 Hydrogen peroxide formation and stoichiometry of hydroxylation reactions catalyzed by highly purified liver microsomal cytochrome P-450 Nordblom,G.D.;Coon,M.J.
  23. Ana. Biochem. v.95 Assay for lipid peroxides in animal tissues by thiobarbituric and reaction Ohakawa,H.;Ohishi,N.;Yagi,K. https://doi.org/10.1016/0003-2697(79)90738-3
  24. J. Lab. Clin. Med. v.70 Studies on the quantitative and qualitative characterization of erythtocyte glutathione peroxidase Paglia,D.E.;Valentine,W.N.
  25. Int. Arch. Occup. Environ. Health v.45 Lung uptake and metabolism of cyclohexane in shoe factory workers Perbellini,L.;Brugnone,F. https://doi.org/10.1007/BF00380789
  26. Int. Arch. Occup. Environ. Health v.72 Biological monitoring of occupational exposure to cyclohexane by urinary 1.2- and 1,4-cyclohexanediol determination Perico,A.;Cassinelli,C.;Brugnone,F.;Bavazzano,P.;Perbellini,L. https://doi.org/10.1007/s004200050346
  27. Gastroenterol v.62 Disparate responses of serum and hepatic alkaline phosphatase asd 5' nucleotidase to bile duct obstruction in the rat Righetti,A.;Kaplan,M.M.
  28. Am. J. Clin. Pathol. v.28 A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminase Reitman,S.;Frankel,S. https://doi.org/10.1093/ajcp/28.1.56
  29. Am. J. Pathol. v.42 Cell proliferation and fiber formation in chronic carbon tetrachloride intoxication, a morphologic and chemical study Rubin,E.;Hutterer,F.;Popper,H.
  30. J. Toxicol. Clin. Toxicol. v.27 Disposition of acetone, methyl ethyl ketone and cyclohexanone in acute poisoning Sakata,M.;Kikuchi,J.;Haga,M.;Ishiyama,N.;Maeda,T.;Ise,T.;Hikita,N. https://doi.org/10.3109/15563658909038570
  31. Statistics for the biological sciences Schefler,W.C.
  32. Biochem. J. v.227 Quantification of cytochrome P-450-dependent cyclohexane hydroxylase activity in nomal and neoplastic reproductive tissues Senler,T.I.;Dean,W.L.;Murray,L.F.;Wittliff,J.L. https://doi.org/10.1042/bj2270379
  33. J. Biol. Chem. v.256 Hydrogen peroxide causes the fetal injury to human fibroblasts exposed to oxygen radicals Simon,R.H.;Scoggin,C.H.;Patterson,D.
  34. Am. Ind. Hyg. Assoc. J. v.30 Range-finding toxicity data: List VII Smyth,H.F.Jr.;Carpenter,C.P.;Weil,C.S.;Pozzani,U.C.;Striegel,J.A.;Nycum,J.S.
  35. Inhalation. J. Ind. Hyg. Toxicol. v.25 The physiological response of animals to cyclohexane, methylcyclohexane and certain derivatives of these compounds.II. Treon,J.F.Jr.;Crutchfield,W.E.;Kitzmiller,K.V.
  36. Hepatology Metabolism of xenobiotics by the human liver Vessey,D.A.;D.Zakim(ed.);T.D.Boyer(ed.)
  37. Keimyung Res. J. v.2 A modified colorimetric assay for xanthine oxidase in rat liver exatracts Yoon,C.G.
  38. 한국독성학회지 v.15 CCl₄에 의한 간손상 정도 차이에 따른 Xylene 대사 변동 이혜자;윤종국;박원학
  39. 한국환경위생학회지 v.25 흰쥐에 있어서 사염화탄소에 의한 간손상이 Xylene 대사에 미치는 영향 이혜자;조현국;윤종국
  40. 박사학위논문, 영남대학교 흰쥐에 사염화탄소 투여시 Xanthine Oxidase 활성 변동에 관한 연구 윤종국
  41. 계명대학교 기초과학연구논집 v.7 흰쥐에 사염화탄소에 의한 간 손상시 Actinomycin 및 Prednisolone 이 혈청 Xanthine Oxidase 활성에 미치는 영향 윤종국
  42. 한국노화학회지 v.8 성장기간이 다른 흰쥐에 사염화탄소 투여가 Oxygen Free Radical 생성계 및 해독계 효소 활성에 미치는 영향 윤종국;이미경;이상일
  43. 계명대학교 기초과학연구논집 v.18 간손상 실험동물 모델에서 Xylene 투여가 혈청 Xanthine Oxidase 활성에 미치는 영향 윤종국;전태원;이혜자
  44. 대한의생명과학회지 v.6 Cyclohexane에 의한 흰쥐의 폐독성 전태원;이상일;윤종국