Low molecular weight catalytic metalloporphyrin antioxidant AEOL 10150 protects lungs from fractionated radiation.

Published

Journal Article

The objective of this study was to determine whether administration of a catalytic antioxidant, Mn(III) tetrakis(N,N'-diethylimidazolium-2-yl) porphyrin, AEOL10150, reduces the severity of long-term lung injury induced by fractionated radiation (RT). Fisher 344 rats were randomized into five groups: RT+AEOL10150 (2.5 mg/kg BID), AEOL10150 (2.5 mg/kg BID) alone, RT+ AEOL10150 (5 mg/kg BID), AEOL10150 (5 mg/kg BID) alone and RT alone. Animals received five 8 Gy fractions of RT to the right hemithorax. AEOL10150 was administered 15 min before RT and 8 h later during the period of RT treatment (5 days), followed by subcutaneous injections for 30 days, twice daily. Lung histology at 26 weeks revealed a significant decrease in lung structural damage and collagen deposition in RT+AEOL10150 (5 mg/kg BID) group, in comparison to RT alone. Immunohistochemistry studies revealed a significant reduction in tissue hypoxia (HIF1alpha, CAIX), angiogenic response (VEGF, CD-31), inflammation (ED-1), oxidative stress (8-OHdG, 3-nitrotyrosine) and fibrosis pathway (TGFbeta1, Smad3, p-Smad2/3), in animals receiving RT+ AEOL10150 (5 mg/kg BID). Administration of AEOL10150 at 5 mg/kg BID during and after RT results in a significant protective effect from long-term RT-induced lung injury. Low dose (2.5 mg/kg BID) delivery of AEOL10150 has no beneficial radioprotective effects.

Full Text

Duke Authors

Cited Authors

  • Rabbani, ZN; Salahuddin, FK; Yarmolenko, P; Batinic-Haberle, I; Thrasher, BA; Gauter-Fleckenstein, B; Dewhirst, MW; Anscher, MS; Vujaskovic, Z

Published Date

  • November 2007

Published In

Volume / Issue

  • 41 / 11

Start / End Page

  • 1273 - 1282

PubMed ID

  • 17957541

Pubmed Central ID

  • 17957541

International Standard Serial Number (ISSN)

  • 1071-5762

Digital Object Identifier (DOI)

  • 10.1080/10715760701689550

Language

  • eng

Conference Location

  • England