Skip to main content
SpringerLink
Log in

Can trifluoperazine protect mitochondria against reactive oxygen species-induced damage?

  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Summary

Trifluoperazine (TFP) (35 μM) prevents mitochondrial transmembrane potential (δϕ) collapse and swelling induced by 10μM Ca2+ plus oxyradicals generated from σ-aminolevulinic acid autoxidation. In contrast with EGTA, TFP cannot restore the totally collapsed δΦ. So, TFP might not remove Ca2+ from its ‘harmful site’, but could impair the ROS-driven cross-linking between membrane-SH proteins. Our data are correlated with the protective uses of TFP against oxidative processes promoted by oxyradicals plus Ca2+.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

EGTA:

ethyleneglycol bis (β-amino-ethyl ether) N, N′-tetraacetic acid

TPP+ :

tetraphenylphosphonium

HEPES:

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid

RLM:

rat liver mitochondria

δΦ:

transmembrane electrical potential

References

  1. Pereira R.S., Bertocchi A.P.F., Vercesi A.E. (1992): Protective effect of trifluoperazine on the mitochondrial damage induced by Ca2+ plus prooxidants. Biochem. Pharmacol., 44, 1795–1801.

    Article  PubMed  CAS  Google Scholar 

  2. Orrenius S, McConkey D.J., Bellomo G., Nicotera P. (1989): Role of Ca2+ in toxic cell killing. Trans. Pharmacol. Sci., 10, 281–285.

    Article  CAS  Google Scholar 

  3. Gunter T.E., Pfeiffer D.R. (1990): Mechanisms by which mitochondria transport calcium. Am. J. Physiol., 258, C755-C786.

    PubMed  CAS  Google Scholar 

  4. Hermes-Lima M., Valle V.G.R., Vercesi A.E., Bechara E.J.H. (1991): Damage to rat liver mitochondria promoted by σ-aminolevulinic acid-generated reactive oxygen species: connections with acute intermittent porphyria and lead-poisoning. Biochim. Biophys. Acta, 1056, 57–63.

    Article  PubMed  CAS  Google Scholar 

  5. Hermes-Lima M., Castilho R.F., Valle V.G.R., Bechara E.J.H., Vercesi A.E. (1992): σ-aminolevulinic acid induces a Ca2+-dependent mitochondrial oxidative stress antagonized by Mg2+: a model for acute intermittent porphyria. Biochim. Biophys. Acta, 1180, 201–206.

    PubMed  CAS  Google Scholar 

  6. Medeiros M.H.G., Mascio P.D., Gründel S., Soboll S., Sies H., Bechara E.J.H. (1994): Catabolism of 5-aminolevulinic acid to CO2 by rat liver mitochondria. Arch. Biochem. Biophys., 310, 205–209.

    Article  PubMed  CAS  Google Scholar 

  7. Valle V.G.R., Fagian M.M., Parentoni L.S., Meinicke A.R.m Vercesi A.E. (1993): The participation of reactive oxygen species and protein thiols in the mechanism of mitochondrial inner membrane permeabilization by calcium plus prooxidants. Arch. Biochem. Biophys., 307, 1–7.

    Article  PubMed  CAS  Google Scholar 

  8. Fagian M.M., Pereira-de-Silva L., Martins I.S., Vercesi A.E. (1990): Membrane protein thiol cross-linking associated with the permeabilization of the inner mitochondrial membrane by Ca2+ plus prooxidants. J. Biol. Chem., 265, 19955–19960.

    PubMed  CAS  Google Scholar 

  9. Kamo N., Muratsugo M., Ruji H., Kobatake J. (1979): Membrane potential of mitochondria measured with an electrode sensitive to tetraphenylphosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady-state. J. Membr. Biol., 48, 105–121.

    Google Scholar 

  10. Muratsugu M., Kamo K., Kurihara K., Kobatake J. (1977): Selective electrode for dibenzyl ammonium cation as indicator of membrane potential in biological systems. Biochim. Biophys. Acta, 464, 613–619.

    Article  PubMed  CAS  Google Scholar 

  11. Jensen B.D., Gunter K.K., Gunter T.E. (1986): The efficiencies of the component steps of oxidative phosphorylation. II. Experimental determination of the efficiencies in mitochondria and examination of the equivalence of membrane potential and pH gradient in phosphorylation. Arch. Biochem. Biophys., 248, 305–323.

    Article  PubMed  CAS  Google Scholar 

  12. Strzelecki T., McGraw B.R., Khauli R.B. (1990): Comparison of the effect of cyclosporine, verapamil and trifluoperazine on calcium-induced membrane permeability of mitochondria. Transplant Proc., 21, 182–183.

    Google Scholar 

  13. Vale M.G.P., Moreno A.J.M., Carvalho A.P. (1983): Effect of calmodulin antagonists on the active Ca2+ uptake by rat liver mitochondria. Biochem. J., 214, 929–935.

    PubMed  CAS  Google Scholar 

  14. Kosower N.S., Kosower E.M. (1978): The glutathione status of cells. Int. Rev. Cytol., 54, 109–160.

    Article  PubMed  CAS  Google Scholar 

  15. Beitner R., Chen-Zion M., Sofer-Bassukevitz Y., Morgenstern H., Ben-Porat H. (1989): Treatment of frostbite with calmodulin antagonists thioridazine and trifluoperazine, Gen. Pharmacol., 20, 641–646.

    PubMed  CAS  Google Scholar 

  16. Manson P.N., Jesudass R., Marzella L., Burkley G.B., Im M.J., Narayan K.K. (1991): Evidence for an early radical-mediated reperfusion injury in frostbite. Free Rad. Biol. Med., 10, 7–11.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Instituto de Química, Universidade Estadual Paulista (UNESP), Campus de Araraquara, CP. 355, CEP 14801-970, Araraquara, SP, Brazil

    R. De Souza Pereira

  2. Oxygen Radicals Research Group, Departmento de Biologia Celular, Universidade de Brasília (UnB), Brasília, DF, Brazil

    M. Hermes-Lima

Authors
  1. R. De Souza Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Hermes-Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Souza Pereira, R., Hermes-Lima, M. Can trifluoperazine protect mitochondria against reactive oxygen species-induced damage?. European Journal of Drug Metabolism and Pharmacokinetics 21, 281–284 (1996). https://doi.org/10.1007/BF03189728

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03189728

Keywords

Search

Navigation