Protective role of ortho-substituted Mn(III) N-alkylpyridylporphyrins against the oxidative injury induced by tert-butylhydroperoxide.
The present work addresses the role of two ortho-substituted Mn(III) N-alkylpyridylporphyrins, alkyl being ethyl in MnTE-2-PyP(5+) and n-hexyl in MnTnHex-2-PyP(5+), 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 O(2)*- generation (dihydroethidium assay) and glutathione status (DTNB and monochlorobimane assays). MnPs per se did not show cytotoxicity (up to 25 microM, 24 h). The exposure to TBHP resulted in a significant decrease in cell viability and in an increase in the intracellular O(2)(*-) 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 O(2)(*-) 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.
Fernandes
Ana S
AS
iMed.UL, Faculty of Pharmacy, University of Lisbon, Lisboa, Portugal.
Gaspar
Jorge
J
Cabral
M Fátima
MF
Rueff
José
J
Castro
Matilde
M
Batinic-Haberle
Ines
I
Costa
Judite
J
Oliveira
Nuno G
NG
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
D000975:Antioxidants; D008665:Metalloporphyrins; C521294:Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin; C431023:manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin; D013481:Superoxides; D020122:tert-Butylhydroperoxide; D005978:Glutathione; D019803:Glutathione Disulfide