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.