Overexpression of extracellular superoxide dismutase reduces acute radiation induced lung toxicity

Rabbani, Zahid N.; Anscher, Mitchell S.; Folz, Rodney J.; Archer, E; Huang, Hong; Chen, Liguang; Golson, Maria L.; Samulski, T.V.; Dewhirst, Mark W.; Vujašković, Željko

doi:10.1186/1471-2407-5-59

Cited by 90 publications

(68 citation statements)

References 47 publications

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“…response [115,116]. In addition, mice over expressing a transgene for human MnSOD were also protected against radiation induced lung damage and showed decreased levels of mRNA for IL-1, TNF-α, and TGF-β.…”

Section: Protection Against Oxidative Damage -Sod and Sod Mimeticsmentioning

confidence: 89%

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Effects of genistein following fractionated lung irradiation in mice

Para¹,

Bezjak²,

Yeung³

et al. 2009

Radiotherapy and Oncology

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Radiation therapy for lung cancer and cancers of the upper thorax is limited by side effects to normal tissue of the lung. An understanding of mechanisms leading to radiation induced lung damage is essential to developing protective agents. In this thesis an anti-oxidant and anti-inflammatory agent Genistein was investigated for its potential to affect DNA damage, tissue inflammation, functional deficits and survival. We hypothesized that chronic oxidative stress and the subsequent inflammatory response play a key role in the development of major lung complications, radiation pneumonitis and fibrosis. If side effects of radiation could be reduced, then larger doses could be delivered to the tumor with a better chance of eradicating the disease.ii Acknowledgements

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Section: Protection Against Oxidative Damage -Sod and Sod Mimeticsmentioning

confidence: 89%

“…In addition, transgenic mice over expressing extracellular (EC)-SOD in alveolar and airway epithelial cells showed protection from radiation injury due to an increased anti-oxidant capacity and decreased inflammatory response [116].…”

Section: Introductionmentioning

confidence: 99%

Effects of genistein following fractionated lung irradiation in mice

Para¹,

Bezjak²,

Yeung³

et al. 2009

Radiotherapy and Oncology

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“…(Figure 2). RT+PBS and RT+1mg/kg/day AEOL 10150 animals, however, demonstrated significantly less weight gain beginning at week 14 compared to the higher doses (10 or 30mg/kg/day) animals (RT+PBS and RT+1mg/kg/day vs. RT+10mg/kg/day at [14][15][16][17][18][19][20] (Figure 2). …”

Section: Long-term Drug Administrationmentioning

confidence: 99%

Long-Term Administration of a Small Molecular Weight Catalytic Metalloporphyrin Antioxidant AEOL 10150 Protects Lungs From Radiation-Induced Injury

Rabbani

Batinić‐Haberle

Poulton

et al. 2005

International Journal of Radiation Oncology*Biology*Physics

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Purpose-To determine whether administration of a catalytic antioxidant, Mn(III) tetrakis(N,N′-diethylimidazolium-2-yl) porphyrin, AEOL 10150, with SOD mimetic properties reduces the severity of radiation-induced injury to the lung from single dose irradiation (RT) of 28 Gy.Materials/Methods-Animals were randomly divided into four different dose groups (0, 1, 10 and 30 mg/kg/day of AEOL 10150), receiving either short (1 week) or long-term (10 weeks) drug administration via osmotic pumps. Animals received single dose irradiation (RT) of 28 Gy to the right hemithorax. Breathing rates, body weights, blood samples, histopathology and immunohistochemistry were used to assess lung damage.Results-There was no significant difference in any of the study endpoints between the irradiated controls and the 3 groups receiving RT and short-term administration of AEOL 10150. For the long term administration functional determinants of lung damage 20 weeks post radiation were significantly worse for RT+PBS and RT+1mg/kg/day of AEOL 10150 as compared to the irradiated groups treated with higher doses of AEOL 10150 (10 or 30mg/kg/day), Lung histology at 20 weeks revealed a significant decrease in structural damage and collagen deposition in animals receiving 10 or 30mg/kg/day after radiation in comparison to RT+PBS and 1mg/kg/day groups. Immunohistochemistry demonstrated a significant reduction in macrophage accumulation, oxidative stress and hypoxia in animals receiving AEOL 10150 (10 or 30mg/kg/day) after lung irradiation compared to RT+PBS and 1mg/kg/day groups. Conclusion-The chronic administration of novel catalytic antioxidant, AEOL 10150, demonstrates a significant protective effect from radiation-induced lung injury. AEOL 10150 has its primary impact on the cascade of events following irradiation and adding drug prior to irradiation and its short-term administration have no significant additional benefits.

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“…Notably, EC-SOD is known to protect the lung against pulmonary injury from bleomycin (5,9,10), asbestos (12,27), radiation (17,25), hyperoxia (6,13,23), hemorrhage (2,3), endotoxin (4,29), and bacteria (28). Proteolysis of the heparinbinding domain of EC-SOD has also been noted in a number of interstitial lung disease models and results in the depletion of EC-SOD from the lung parenchyma and accumulation of proteolyzed EC-SOD in the bronchoalveolar lavage fluid (BALF) (10,27).…”

mentioning

confidence: 99%