Protective role of ortho-substituted Mn(III) N-alkylpyridylporphyrins against the oxidative injury induced by tert-butylhydroperoxide

Abstract

The present work addresses the role of two ortho-substituted Mn(III) N-alkylpyridylporphyrins, alkyl being ethyl in MnTE-2-PyP⁵⁺ and n-hexyl in MnTnHex-2-PyP⁵⁺, on the protection against the oxidant tert-butylhydroperoxide (TBHP). Their protective role was studied in V79 cells using endpoints of cell viability (MTT and crystal violet assays), intracellular O₂•– generation (dihydroethidium assay) and glutathione status (DTNB and monochlorobimane assays). MnPs per se did not show cytotoxicity (up to 25 μM, 24 h). The exposure to TBHP resulted in a significant decrease in cell viability and in an increase in the intracellular O₂^•– levels. Also, TBHP depleted total and reduced glutathione and increased GSSG. The two MnPs counteracted remarkably the effects of TBHP. Even at low concentrations, both MnPs were protective in terms of cell viability and abrogated the intracellular O₂^•– increase in a significant way. Also, they augmented markedly the total and reduced glutathione contents in TBHP-treated cells, highlighting the multiple mechanisms of protection of these SOD mimics, which at least in part may be ascribed to their electron-donating ability.

Keywords::

• MnTE-2-PyP
• MnTnHex-2-PyP
• superoxide dismutase mimetic
• tert-butylhydroperoxide
• cytotoxicity
• glutathione

Declaration of interest: A. S. F. acknowledges Fundação para a Ciência e a Tecnologia, Portugal, for financial support (PhD grant SFRH/BD/28773/2006). Ines Batinic-Haberle is thankful to Wallace H. Coulter Translational Partners Grant Program. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This paper was first published online on Early Online on 26 January 2010.