Effects of 3-Amino-1,2,4 Triazole and Diethyldithiocarbamate on Paraquat Toxicity in Rats

흰쥐에서 Aminotriazole과 Diethyldithiocarbamate가 Paraquat의 독성에 미치는 영향

  • 차종희 (조선대학교 의과대학 생화학교실) ;
  • 고광삼 (조선대학교 의과대학 생화학교실)
  • Published : 1997.12.01

Abstract

The effects of superoxide dismutase(SOD) and catalase on the toxicity of paraquat(PQ) were studied using diethyldithiocarbamate(DDC), 3-amino-1,2,4-triazole(AT) which are inhibitors of Cu, Zn-SOD and catalase in rats. Sprague Dawley rats were divide into 6 groups: control, DDC, PQ, AT, DDC+PQ, and AT+PQ group. The PQ (50 mg/kg body weight(BW); about half dose of $LD_{50}$) was administered with orally, otherwise AT(1.0g/kg BW) and DDC(1.0g/kg BW) were administered by intrperitoneal(iP) injection. The survival rate of rats in PQ+AT group was significantly decreased compared with PQ group while the difference of survival rate between DDC group and DDC+PQ group was not significant. The SOD activity after administration of DDC was decreased in liver, lung and kidney, but catalase activity was not changed. The catalase activity in liver, lung and kidney of AT treated rats was decreased, while SOD activity was not changed in this group. The effects of DDC and AT to the PQ toxicity was also observed in primary cultured rat Skin fibroblasts. The viable cells that was measured with MTT method, was decreased in AT+PQ treated group compared to PQ treated group, but the difference of cell viability between DDC treat group and DDC+PQ treated group was not observed. This result, AT potentlate PQ toxicity while DDC were not affect, suggested that the decreased catalase activity lead to elevation of hydrogen peroxide levels and PQ toxicity may be correlate with the hydrogen peroxide rather than the superoxides.

Keywords

References

  1. Catalase, Methods of Enzymatic analysis v.3 Aebi, H.;Bergmeyer, H.U.(ed.);Bergmeyer, J.(ed.);GralBl, M.(ed.)
  2. Biochem. Biophys. Res. Comman. v.58 Superoxide and singlet oxygen-catalyed lipid peroxidation as a possible mechanism for paraquat (methy viologen) toxicity Bus, J.S.;Aust, S.D.;Gibson, J.E.
  3. Cancer Res. v.47 Evaluation of a tetrazolium-based semiautomated colorimetric assay : assessment of chemosensitivity testing Carmichael, J.W.;Degraff, W.G.;Gazdar, A.F.;Minna, J.D.;Michell, J.B.
  4. Methods in Enzymology v.53 Preparation and assay of superoxide dismutase Crapo, J.D.;McCord, J.M.;Fridovich, I.;Fleischer, S.(ed.);Packer, L.(ed.)
  5. Physiol. Rev. v.50 Catalase physical and chemical properties mechanism of catalysis and physiological role Deisseroth, A.;Dounce, A.L.
  6. Proc. Natl. Acad. Sci. USA v.68 Compounds I of catalase horseradish peroxidase Dolphin, D.;Forman, A.;Berg, D.C.;Fajce, J.;Felton, R.H.
  7. Culture of animal cells Disaggregation of the tissue and Primary culture Freshney, R.I.
  8. Annu. Rev. Biochem. v.44 Superoxide dxmutase Fridovich, I.
  9. J. Biol. chem. v.264 Superoxide dismutase Fridovich, I.
  10. Am. J. Physiol. v.256 In vivo generation of hydrogen peroxide by rat kidney cortex and glomeruli Guidet, B.R.;Shah, S.V.
  11. Am. Physiol. v.257 Enhanced In vivo H₂O₂ generation by rat kidney in glycerol induced renal failure Guidet, B.R.;Shah, S.V.
  12. Methods in Enzymology v.186 Rales of free radicals and caralytic metalinos in human disease Halliwell, B.;Gutterridge, J.M.C.
  13. J. Biol. Chem. v.253 Superoxide radical and oxygen enhancemen of the toxicity of paraquat in escherica coli Hassan, H.M.;Fridovich, I.
  14. Arch. Biochem. Biophys. v.210 Metabolism of hydrogen peroxide in isolated hepatocytes : relative contributions of catalase and glutathione peroxidase in decomposition of endogenously generated H₂O₂ Jones, D.P.;Eklow, L.;Thor, H.;Orrenius, S.
  15. J. Biol. Chem. v.261 Inhibition of erythrocyte superoxide by diethyldithiocarbamate also results in oxyhemoglobin-catalyzed glutathione depletion and methemoglobin production Kelner, M.J.;Alexander, N.M.
  16. J. Biol. chem. v.265 Alteration of endogenous glutathione peroxidase, manganese superoxide dismutase expression vector. Explanation for variations in paraquat resistance Kelner, M.J.;Bagnell, R.
  17. Toxicol. Appl. Pharmacol. v.53 The effect of paraquat on microsomal lipid peroxidation in vitro and in vivo Kornbrust, D.J.;Mavis, R.D.
  18. J. Biol. Chem. v.193 Protein measurement with folin phenol reagent Lowry, C.H.;Rosebrough, N.J.;Farr, A.L.;Radall, R.J.
  19. Ann. Rev. Biochem. v.52 Glutathione Meister, A.;anderson, M.E.
  20. Superoxide dismutase and cancer, superoxide dismutse Oberley, L.W.(ed.)
  21. Proc. Natl. Acad. Sci. v.86 Null mutation of copper/Zinc superoxide dismutase in drosophila cofers hypersensitivity to paraquat and radical longevity Phillips, J.P.;Campbell, S.D.;Michard, D.;Charbonneau, M.;Hilliker, A.J.
  22. Free radical and human disease, in CRC handbook of free radical and antioxidants in biomedicine v.1 Proctor, P.H.;Miguel, J.(ed.);Quintanilha, A.T.(ed.);Weber, H.(ed.)
  23. Proc. Natl. Acad. Sci. v.87 Overexpression of Cu-Zn superoxide dismutase in Drosophila does not affect life-span Seto, N.O.;Hayashi, S.;Tener, G.M.
  24. FEBS Lett. v.293 Overproduction of human Mn-Superoxide modulates paraquat mediated toxicity in mammalian cells StClair, D.K.;Oberley, T.D.;Ho, Y.S.
  25. 대한화학회지 v.38 일차배양 백서 피부섬유아세포에서 paraquat독성에 미치는 SOD와 catalase의 영향 차종희;유의경