Publications [#169024] of Mark W. Dewhirst

Papers Published

1. ZN Rabbani, I Batinic-Haberle, MS Anscher, J Huang, BJ Day, E Alexander, MW Dewhirst, Z Vujaskovic, Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant, AEOL 10150, protects lungs from radiation-induced injury., International journal of radiation oncology, biology, physics, United States, vol. 67 no. 2 (February, 2007), pp. 573-80, ISSN 0360-3016
   (last updated on 2009/12/31)

   Abstract:
   PURPOSE: To determine whether administration of a catalytic antioxidant, Mn(III) tetrakis(N,N'-diethylimidazolium-2-yl) porphyrin, AEOL 10150, with superoxide dismutase (SOD) mimetic properties, reduces the severity of radiation-induced injury to the lung from single-dose irradiation (RT) of 28 Gy. METHODS AND MATERIALS: Rats were randomly divided into four different dose groups (0, 1, 10, and 30 mg/kg/day of AEOL 10150), receiving either short-term (1 week) or long-term (10 weeks) drug administration via osmotic pumps. Rats 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 three groups receiving RT and short-term administration of AEOL 10150. For the long-term administration, functional determinants of lung damage 20 weeks postradiation were significantly worse for RT + phosphate-buffered saline (PBS) and RT + 1 mg/kg/day of AEOL 10150 as compared with the irradiated groups treated with higher doses of AEOL 10150 (10 or 30 mg/kg/day). Lung histology at 20 weeks revealed a significant decrease in structural damage and collagen deposition in rats receiving 10 or 30 mg/kg/day after radiation in comparison to the RT + PBS and 1 mg/kg/day groups. Immunohistochemistry demonstrated a significant reduction in macrophage accumulation, oxidative stress, and hypoxia in rats receiving AEOL 10150 (10 or 30 mg/kg/day) after lung irradiation compared with the RT + PBS and 1 mg/kg/day groups. CONCLUSIONS: The chronic administration of a 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 after irradiation, and adding the drug before irradiation and its short-term administration have no significant additional benefits.

   Keywords:
   Animals • Antioxidants • Cell Count • Deoxyguanosine • Female • Lung • Macrophages • Metalloporphyrins • Radiation Injuries • Radiation Injuries, Experimental • Radiation-Protective Agents • Random Allocation • Rats • Rats, Inbred F344 • administration & dosage* • analogs & derivatives • analysis • physiology • prevention & control* • radiation effects*