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• W2046053045 endingPage "1043" @default.
• W2046053045 startingPage "1034" @default.
• W2046053045 abstract "Chronic production of reactive oxygen and nitrogen species is an underlying mechanism of irradiation (IR)-induced lung injury. The purpose of this study was to determine the optimum time of delivery of an antioxidant and redox-modulating Mn porphyrin, MnTE-2-PyP(5+), to mitigate and/or treat IR-induced lung damage. Female Fischer-344 rats were irradiated to their right hemithorax (28 Gy). Irradiated animals were treated with PBS or MnTE-2-PyP(5+) (6 mg /kg/24 h) delivered for 2 weeks by sc-implanted osmotic pumps (beginning after 2, 6, 12, 24, or 72 h or 8 weeks). Animals were sacrificed 10 weeks post-IR. Endpoints were body weight, breathing frequency, histopathology, and immunohistochemistry (8-OHdG, ED-1, TGF-beta, HIF-1alpha, VEGF A). A significant radioprotective effect on functional injury, measured by breathing frequency, was observed for all animals treated with MnTE-2-PyP(5+). Treatment with MnTE-2-PyP(5+) starting 2, 6, and 12 h but not after 24 or 72 h resulted in a significant decrease in immunostaining for 8-OHdG, HIF-1alpha, TGF-beta, and VEGF A. A significant decrease in HIF-1alpha, TGF-beta, and VEGF A, as well as an overall reduction in lung damage (histopathology), was observed in animals beginning treatment at the time of fully developed lung injury (8 weeks post-IR). The catalytic manganese porphyrin antioxidant and modulator of redox-based signaling pathways MnTE-2-PyP(5+) mitigates radiation-induced lung injury when given within the first 12 h after IR. More importantly, this is the first study to demonstrate that MnTE-2-PyP(5+) can reverse overall lung damage when started at the time of established lung injury 8 weeks post-IR. The radioprotective effects are presumably mediated through its ability both to suppress oxidative stress and to decrease activation of key transcription factors and proangiogenic and profibrogenic cytokines." @default.
• W2046053045 created "2016-06-24" @default.
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• W2046053045 date "2010-04-15" @default.
• W2046053045 modified "2023-10-17" @default.
• W2046053045 title "Early and late administration of MnTE-2-PyP5+ in mitigation and treatment of radiation-induced lung damage" @default.
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• W2046053045 doi "https://doi.org/10.1016/j.freeradbiomed.2010.01.020" @default.
• W2046053045 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3704177" @default.
• W2046053045 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20096348" @default.
• W2046053045 hasPublicationYear "2010" @default.
• W2046053045 type Work @default.

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