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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Abbreviations
- CV:
-
Crystal violet
- DHE:
-
Dihydroethidium
- Dox:
-
Doxorubicin
- MI:
-
Mitotic index
- MnPs:
-
Manganese porphyrins
- MnTM-4-PyP:
-
Manganese(III)tetrakis-(1-methyl-4-pyridyl) porphyrin
- MTT:
-
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide
- ROS:
-
Reactive oxygen species
- SOD:
-
Superoxide dismutase
- SODm:
-
Superoxide dismutase mimetics
- TBHP:
-
tert-Butylhydroperoxide
- XXO:
-
Xanthine/xanthine oxidase system
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Acknowledgments
A.S.F. acknowledges Fundação para a Ciência e a Tecnologia, Portugal for the financial support (PhD grant SFRH/BD/28773/2006).
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Fernandes, A.S., Serejo, J., Gaspar, J. et al. Oxidative injury in V79 Chinese hamster cells: protective role of the superoxide dismutase mimetic MnTM-4-PyP. Cell Biol Toxicol 26, 91–101 (2010). https://doi.org/10.1007/s10565-009-9120-3
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DOI: https://doi.org/10.1007/s10565-009-9120-3