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 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.

• Authors: Zahid N Rabbani, Ines Batinic-Haberle, Mitchell S Anscher, Jie Huang, Brian J Day, Elaine Alexander, Mark W Dewhirst, Zeljko Vujaskovic
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 67 Issue 2 Pg. 573-80 (Feb 01 2007) ISSN: 0360-3016 [Print] United States
• PMID: 17236973 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• AEOL 10150
• Antioxidants
• Metalloporphyrins
• Radiation-Protective Agents
• 8-Hydroxy-2'-Deoxyguanosine
• Deoxyguanosine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Animals
• Antioxidants (administration & dosage)
• Cell Count
• Deoxyguanosine (analogs & derivatives, analysis)
• Female
• Lung (radiation effects)
• Macrophages (physiology)
• Metalloporphyrins (administration & dosage)
• Radiation Injuries (prevention & control)
• Radiation Injuries, Experimental (prevention & control)
• Radiation-Protective Agents (administration & dosage)
• Random Allocation
• Rats
• Rats, Inbred F344