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Title: Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant, AEOL 10150, protects lungs from radiation-induced injury

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 themore » 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.« less

Authors:
 [1];  [1];  [1];  [2];  [2];  [3];  [1];  [4]
  1. Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)
  2. Department of Medicine, National Jewish Medical and Research Center, Denver, CO (United States)
  3. Aeolus Pharmaceuticals, Laguna Niguel, CA (United States)
  4. Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States). E-mail: vujas@radonc.duke.edu
Publication Date:
OSTI Identifier:
20944704
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2006.09.053; PII: S0360-3016(06)03233-0; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANOXIA; ANTIOXIDANTS; BIOLOGICAL STRESS; BLOOD; CHRONIC INTAKE; COLLAGEN; DAMAGE; DRUGS; HISTOLOGY; INJURIES; IRRADIATION; LUNGS; MACROPHAGES; OXIDATION; PORPHYRINS; RADIATION DOSES; RATS; RESPIRATION; SUPEROXIDE DISMUTASE; TOXICITY

Citation Formats

Rabbani, Zahid N., Batinic-Haberle, Ines, Anscher, Mitchell S., Huang Jie, Day, Brian J., Alexander, Elaine, Dewhirst, Mark W., and Vujaskovic, Zeljko. Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant, AEOL 10150, protects lungs from radiation-induced injury. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.09.053.
Rabbani, Zahid N., Batinic-Haberle, Ines, Anscher, Mitchell S., Huang Jie, Day, Brian J., Alexander, Elaine, Dewhirst, Mark W., & Vujaskovic, Zeljko. Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant, AEOL 10150, protects lungs from radiation-induced injury. United States. doi:10.1016/j.ijrobp.2006.09.053.
Rabbani, Zahid N., Batinic-Haberle, Ines, Anscher, Mitchell S., Huang Jie, Day, Brian J., Alexander, Elaine, Dewhirst, Mark W., and Vujaskovic, Zeljko. Thu . "Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant, AEOL 10150, protects lungs from radiation-induced injury". United States. doi:10.1016/j.ijrobp.2006.09.053.
@article{osti_20944704,
title = {Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant, AEOL 10150, protects lungs from radiation-induced injury},
author = {Rabbani, Zahid N. and Batinic-Haberle, Ines and Anscher, Mitchell S. and Huang Jie and Day, Brian J. and Alexander, Elaine and Dewhirst, Mark W. and Vujaskovic, Zeljko},
abstractNote = {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.},
doi = {10.1016/j.ijrobp.2006.09.053},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 67,
place = {United States},
year = {Thu Feb 01 00:00:00 EST 2007},
month = {Thu Feb 01 00:00:00 EST 2007}
}