Development of
radiation therapy (RT)-induced
lung injury is associated with chronic production of reactive
oxygen and
nitrogen species (ROS/RNS).
MnTE-2-PyP5+ is a catalytic Mn
porphyrin mimic of SOD, already shown to protect lungs from RT-induced injury by scavenging ROS/RNS. The purpose of this study was to compare
MnTE-2-PyP5+ with a newly introduced analogue MnTnHex-2-PyP5+, which is expected to be a more effective radioprotector due to its lipophilic properties. This study shows that Fischer rats which were irradiated to their right hemithorax (28 Gy) have less
pulmonary injury as measured using breathing frequencies when treated with daily
subcutaneous injections of
MnTE-2-PyP5+ (3 and 6 mg/kg) or
MnTnHex-2-PyP5+ (0.3, 0.6, or 1.0 mg/kg) for 2 weeks after RT. However, at 16 weeks post-RT, only
MnTE-2-PyP5+ at a dose of 6 mg/kg is able to ameliorate oxidative damage, block activation of HIF-1alpha and
TGF-beta, and impair upregulation of CA-IX and
VEGF.
MnTnHex-2-PyP5+ at a dose of 0.3 mg/kg is effective only in reducing RT-induced
TGF-beta and CA-IX expression. Significant loss of
body weight was observed in animals receiving
MnTnHex-2-PyP5+ (0.3 and 0.6 mg/kg).
MnTnHex-2-PyP5+ has the ability to dissolve
lipid membranes, causing local irritation/
necrosis at injection sites if given at doses of 1 mg/kg or higher. In conclusion, both compounds show an ability to ameliorate lung damage as measured using breathing frequencies and histopathologic evaluation. However,
MnTE-2-PyP5+ at 6 mg/kg proved to be more effective in reducing expression of key molecular factors known to play an important role in radiation-induced
lung injury.