1887

Abstract

Summary: The nitro radical-anion of the anti-trichomonal drug metronidazole has been detected by electron spin resonance spectrometry under anaerobic conditions in suspensions of intact hydrogenosomes isolated from the parasitic protozoon . Metronidazole reduction was driven by pyruvate, but progressive damage to the radical generating system was observed. Quenching of signals due to metronidazole radicals by chromium oxalate suggests that the radicals generated within the organelle can cross the hydrogenosomal membrane into the external medium. Even if a similar process of radical migration occurs , it seems likely that intrahydrogenosomal damage may explain drug action.

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1985-09-01
2024-10-11
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References

  1. Berg S. P., Nesbitt D. M. 1979; Chromium oxalate: a new spin label broadening agent for use with thylakoids. Biochimica et biophysica acta 548:608–615
    [Google Scholar]
  2. Breccia A., Cavalleri B., Adams G. E. (editors) 1982; Nitroimidazoles; Chemistry, Pharmacology and Clinical Applications. New York: Plenum;
    [Google Scholar]
  3. Cammack R., Kerscher L., Oesterhelt D. 1980; A stable free radical intermediate in the reaction of2 oxoacid: ferredoxin oxidoreductase of Halobacter ium halobium. FEBS Letters 118:271–273
    [Google Scholar]
  4. ČErkasov J., ČErkasovova A., Kulda J., Vilhel Mova D. 1978; Respiration of hydrogenosomes of Tritrichomonas foetus. I. ADP dependent oxidation of malate and pyruvate. Journal of Biological Chemistry 253:1207–1214
    [Google Scholar]
  5. Edwards D. I. 1979; Mechanism of antimicrobial action of metronidazole. Journal of Antimicrobial Chemotherapy 5:499–502
    [Google Scholar]
  6. Gorrell T. E., Yarlett N., Moller M. 1984; Isolation and characterisation of Trichomonas vaginalis ferredoxin. Carlsberg Research Communications 49:259–268
    [Google Scholar]
  7. Hanks J. H., Wallace R. E. 1949; Relation of O2and temperature in the preservation of tissues by refrigeration. Proceedings of the Society jor Exper imental Biology and Medicine 2:196–200
    [Google Scholar]
  8. Kulda J., Honigberg H. M., Frost J. K., Hollander D. H. 1970; Pathogenicity of Tricho monas vaginalis. A chemical and biologic study. American Journal of Obstetrics and Gynecology 108:908–918
    [Google Scholar]
  9. Lindmark D. G., Moller M. 1973; Hydrogeno some, a cytoplasmic organelle of the anaerobic flagellate Tritrichomonas foetus and its role in pyruvate metabolism. Journal ofBiological Chemistry 248:7724–7748
    [Google Scholar]
  10. Lloyd D., Kristensen B. 1985; Metronidazole inhibition of hydrogen production in vivo in drug sensitive and resistant strains of Trichomonas vagina/is. Journal of General Microbiology 1:849–853
    [Google Scholar]
  11. Lloyd D., Pedersen J. 1985; Metronidazole radical anion generation in vivo in Trichomonas vaginalis: oxygen quenching is enhanced in a drug resistant strain. Journal of General Microbiology 131:87–92
    [Google Scholar]
  12. Lloyd O., Ohnishi T., Lindmark D. G., Moller M. 1983; Respiration of Tritrichomonas foetus. Wiadomosci parazytologiczne 1:37–39
    [Google Scholar]
  13. Marczak R., Gorrell T. E., Moller M. 1983; Hydrogenosomal ferredoxin of the anaerobic protozoon, Tritrichomonas foetus. Journal of Biological Chemistry 258:12427–12433
    [Google Scholar]
  14. Mason R. P., Holtzman J. L. 1975; The mechanism of microsomal and mitochondrial nitro reductase. Electron spin resonance evidence for nitro-aromatic free radical intermediates. Biochemis try 1:1626–1632
    [Google Scholar]
  15. Moreno S. N. J., Mason R. P., Muniz R. P. A., Cruz F. S., Docampo R. 1983; Generation of free radicals from metronidazole and other nitro imidazoles by Tritrichomonas foetus. Journal of Biological Chemistry 258:4051–4054
    [Google Scholar]
  16. Moreno S. N. J., Mason R. P., Docampo R. 1984; Distinct reduction of nitrofurans and metro nidazole to free radical metabolites by Tritricho monasfoetus hydrogenosomal and cytosolic enzymes. Journal of Biological Chemistry 259:8252–8259
    [Google Scholar]
  17. MüLler M. 1983; Mode ofaction ofmetronidazole 17 on anaerobic bacteria and protozoa. Surgery 93:165–171
    [Google Scholar]
  18. MüLler M., Lindmark D. G. 1976; Uptake of metronidazole and its effect on viability in tricho 18 monads and Entamoeba invadens under anaerobic and aerobic conditions. Antimicrobial Agents and Chemotherapy 9:696–700
    [Google Scholar]
  19. Ohnishi T., Lloyd D., Lindmark D. G., Moller M. 1980; Respiration of Trichomonas foetus: com ponents detected in hydrogenosomes and in intactcells by electron paramagnetic resonance spectrometry. Molecular and Biochemical Parasitology 2:39–50
    [Google Scholar]
  20. Perez-Reyes E., Kalyanaraman B., Mason R. P. 1980; The reductive metabolism of metronidazole and ronidazole by aerobic liver microsomes. Molecu lar Pharmacology 17:239–244
    [Google Scholar]
  21. Yarlett N., Gorrell T. E., Marczak R., Moller M. 1985; Reduction of nitroimidazole derivatives by hydrogenosomal extracts of Trichomonas vaginalis. Molecular and Biochemical Para sitology 1:29–40
    [Google Scholar]
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