Oxidative injury in V79 Chinese hamster cells: protective role of the superoxide dismutase mimetic MnTM-4-PyP.
Oxidative cell injury could be induced by different reactive oxygen species (ROS) operating in multiple pathways. The present work is focused on three different models of oxidative stress: the xanthine/xanthine oxidase system (XXO), an extracellular superoxide anion generator; tert-butylhydroperoxide (TBHP), an analogue of lipid hydroperoxides; and doxorubicin (Dox), an anticancer drug. Superoxide and peroxyl radicals, among other ROS, could be effectively scavenged by MnTM-4-PyP, a polyfunctional catalytic antioxidant. In this report, we have addressed the role of MnTM-4-PyP on the protection against the cytotoxicity induced by the three aforementioned oxidants. The effect of MnTM-4-PyP (0.1-100 microM) was evaluated in V79 fibroblasts using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide reduction and the crystal violet assays, as well as the mitotic index. Also, the generation of intracellular ROS was studied by the fluorescent probe dihydroethidium. MnTM-4-PyP has shown significant protective effects against the cytotoxicity of XXO and TBHP, increasing the cell viability in approximately 40% and reducing the intracellular level of ROS. However, no considerable protection occurred against Dox. The three oxidants caused a mitotic index reduction that was not altered by MnTM-4-PyP. In summary, MnTM-4-PyP appears to be a promising agent for the protection against oxidative injury. However, it has shown differential responses, reinforcing the need to study different experimental models for the adequate evaluation of its potentialities as a catalytic antioxidant.
Fernandes
Ana S
AS
iMed.UL, University of Lisbon, Portugal.
Serejo
João
J
Gaspar
Jorge
J
Cabral
Fátima
F
Bettencourt
Ana F
AF
Rueff
José
J
Castro
Matilde
M
Costa
Judite
J
Oliveira
Nuno G
NG
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004317:Doxorubicin / Q000494:pharmacology; D004347:Drug Interactions; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005562:Formazans / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology*; D008345:Manganese; D008665:Metalloporphyrins / Q000378:metabolism / Q000494:pharmacology*; D008940:Mitotic Index; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D019820:Xanthine / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D000970:Antineoplastic Agents; D005562:Formazans; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; C431023:manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin; D019820:Xanthine; C079782:MTT formazan; D008345:Manganese; D004317:Doxorubicin; D020122:tert-Butylhydroperoxide; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase