A small molecular weight catalytic metalloporphyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lungs from radiation-induced injury.
Radiation therapy (RT) is an important therapeutic modality in the treatment of thoracic tumors. The maximum doses to these tumors are often limited by the radiation tolerance of lung tissues. Lung injury from ionizing radiation is believed to be a consequence of oxidative stress and a cascade of cytokine activity. Superoxide dismutase (SOD) is a key enzyme in cellular defenses against oxidative damage. The objective of this study was to determine whether the SOD mimetic AEOL 10113 [manganese (III) mesotetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP(5+))] increases the tolerance of lung to ionizing radiation. AEOL 10113 was able to significantly reduce the severity of RT-induced lung injury. This was strongly supported with histopathology results and measurements of collagen deposition (hydroxyproline content). There was a significant reduction in the plasma level of the profibrogenic cytokine transforming growth factor-beta (TGF-beta) in the group of rats receiving RT + AEOL 10113. In conclusion, the novel SOD mimetic, AEOL 10113, demonstrates a significant protective effect from radiation-induced lung injury.
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. vujas@radonc.duke.edu
Zeljko
Z
Vujaskovic
Ines
I
Batinic-Haberle
Zahid N
ZN
Rabbani
Qin-fu
QF
Feng
Song K
SK
Kang
Ivan
I
Spasojevic
Thaddeus V
TV
Samulski
Irwin
I
Fridovich
Mark W
MW
Dewhirst
Mitchell S
MS
Anscher
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D005609:Free Radicals; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology; D055370:Lung Injury; D008665:Metalloporphyrins / Q000494:pharmacology*; D011832:Radiation Injuries / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D012119:Respiration / Q000528:radiation effects; D013482:Superoxide Dismutase / Q000378:metabolism*; D013899:Thoracic Neoplasms / Q000532:radiotherapy; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism
D000975:Antioxidants; D005609:Free Radicals; D008665:Metalloporphyrins; D016212:Transforming Growth Factor beta; D003094:Collagen; D013482:Superoxide Dismutase; D006909:Hydroxyproline