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A manganese porphyrin complex is a novel radiation protector.
Free Radic Biol Med. 2004 Jul 15; 37(2):272-83.FR

Abstract

Exposure of cells to ionizing radiation leads to formation of reactive oxygen species, which are associated with radiation-induced cytotoxicity. Therefore, compounds that scavenge reactive oxygen species may confer radioprotective effects. Superoxide dismutase (SOD) mimetics have been shown to be protective against cell injury caused by reactive oxygen species. The objective of this study was to investigate the effects of manganese(III) tetrakis(N-methyl-2-pyridyl)porphyrin (MnTMPyP), a cell-permeable SOD mimetic, on radiation-dependent toxicity. We investigated the protective role of MnTMPyP against ionizing radiation in U937 cells and mice. On exposure to ionizing radiation, there was a distinct difference between control cells and cells pretreated with MnTMPyP with respect to viability, cellular redox status, and oxidative damage to cells. Lipid peroxidation, oxidative DNA damage, and protein oxidation were significantly lower in the cells treated with MnTMPyP when the cells were exposed to ionizing radiation. The [GSSG]/[GSH + GSSG] ratio and the generation of intracellular reactive oxygen species were higher and the [NADPH]/[NADP+ + NADPH] ratio was lower in control cells compared with MnTMPyP-treated cells. Ionizing radiation-induced mitochondrial damage, as reflected by the altered mitochondrial permeability transition, increase in accumulation of reactive oxygen species, reduction of ATP production, and morphological change, was significantly higher in control cells than in MnTMPyP-treated cells. MnTMPyP administration for 14 days at a daily dosage of 5 mg/kg provided substantial protection against killing and oxidative damage in mice exposed to whole-body irradiation. These data indicate that MnTMPyP may have great application potential as a new class of in vivo, non-sulfur-containing radiation protectors.

Authors+Show Affiliations

Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702-701, South Korea.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15203198

Citation

Lee, Jin Hyup, and Jeen-Woo Park. "A Manganese Porphyrin Complex Is a Novel Radiation Protector." Free Radical Biology & Medicine, vol. 37, no. 2, 2004, pp. 272-83.
Lee JH, Park JW. A manganese porphyrin complex is a novel radiation protector. Free Radic Biol Med. 2004;37(2):272-83.
Lee, J. H., & Park, J. W. (2004). A manganese porphyrin complex is a novel radiation protector. Free Radical Biology & Medicine, 37(2), 272-83.
Lee JH, Park JW. A Manganese Porphyrin Complex Is a Novel Radiation Protector. Free Radic Biol Med. 2004 Jul 15;37(2):272-83. PubMed PMID: 15203198.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A manganese porphyrin complex is a novel radiation protector. AU - Lee,Jin Hyup, AU - Park,Jeen-Woo, PY - 2004/03/02/received PY - 2004/04/20/revised PY - 2004/04/22/accepted PY - 2004/6/19/pubmed PY - 2005/2/3/medline PY - 2004/6/19/entrez SP - 272 EP - 83 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 37 IS - 2 N2 - Exposure of cells to ionizing radiation leads to formation of reactive oxygen species, which are associated with radiation-induced cytotoxicity. Therefore, compounds that scavenge reactive oxygen species may confer radioprotective effects. Superoxide dismutase (SOD) mimetics have been shown to be protective against cell injury caused by reactive oxygen species. The objective of this study was to investigate the effects of manganese(III) tetrakis(N-methyl-2-pyridyl)porphyrin (MnTMPyP), a cell-permeable SOD mimetic, on radiation-dependent toxicity. We investigated the protective role of MnTMPyP against ionizing radiation in U937 cells and mice. On exposure to ionizing radiation, there was a distinct difference between control cells and cells pretreated with MnTMPyP with respect to viability, cellular redox status, and oxidative damage to cells. Lipid peroxidation, oxidative DNA damage, and protein oxidation were significantly lower in the cells treated with MnTMPyP when the cells were exposed to ionizing radiation. The [GSSG]/[GSH + GSSG] ratio and the generation of intracellular reactive oxygen species were higher and the [NADPH]/[NADP+ + NADPH] ratio was lower in control cells compared with MnTMPyP-treated cells. Ionizing radiation-induced mitochondrial damage, as reflected by the altered mitochondrial permeability transition, increase in accumulation of reactive oxygen species, reduction of ATP production, and morphological change, was significantly higher in control cells than in MnTMPyP-treated cells. MnTMPyP administration for 14 days at a daily dosage of 5 mg/kg provided substantial protection against killing and oxidative damage in mice exposed to whole-body irradiation. These data indicate that MnTMPyP may have great application potential as a new class of in vivo, non-sulfur-containing radiation protectors. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/15203198/A_manganese_porphyrin_complex_is_a_novel_radiation_protector_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891584904003508 DB - PRIME DP - Unbound Medicine ER -