Oxidative injury in V79 Chinese hamster cells: protective role of the superoxide dismutase mimetic MnTM-4-PyP |
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Authors: | Ana S Fernandes João Serejo Jorge Gaspar Fátima Cabral Ana F Bettencourt José Rueff Matilde Castro Judite Costa Nuno G Oliveira |
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Institution: | (1) iMed.UL, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal;(2) CIGMH, Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, Rua da Junqueira 96, 1349-008 Lisbon, Portugal; |
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Abstract: | 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 μM) 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. |
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