Early and late administration of MnTE-2-PyP5+ in mitigation and treatment of radiation-induced lung damage.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gauter-Fleckenstein, B; Fleckenstein, K; Owzar, K; Jiang, C; Rebouças, JS; Batinic-Haberle, I; Vujaskovic, Z

Published Date

  • April 15, 2010

Published In

Volume / Issue

  • 48 / 8

Start / End Page

  • 1034 - 1043

PubMed ID

  • 20096348

Pubmed Central ID

  • 20096348

Electronic International Standard Serial Number (EISSN)

  • 1873-4596

Digital Object Identifier (DOI)

  • 10.1016/j.freeradbiomed.2010.01.020

Language

  • eng

Conference Location

  • United States