Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis
- Medical Radiology Service, Hines VA Hospital, Maywood, IL (United States)
Corticosteroids have previously been found to be protective against the mortality of radiation pneumonitis in mice, even when given well after lethal lung irradiation. The authors explored the possibility that this effect was due to their well-known anti-inflammatory actions by giving various nonsteroidal inhibitors of arachidonate metabolism to groups of mice that had received 19 Gy to the thorax (bilaterally). Treatments of four cyclooxygenase inhibitors, one lipoxygenase inhibitor, and one leukotriene receptor antagonist, given by various routes in various doses, were commenced 10 weeks after irradiation or sham irradiation and continued throughout the period when death from radiation pneumonitis occurs, 11-26 weeks after irradiation. Each of the treatments had the appropriate effect on arachidonate metabolism in the lungs as assessed by LTB4 and PGE2 levels in lung lavage fluid. The principal end point was mortality. The 5-lipoxygenase inhibitor diethylcarbamazine and the LTD4/LTE4 receptor antagonist LY 171883 markedly reduced mortality in dose-response fashion. The effects of cyclooxygenase inhibitors were divergent; piroxicam and ibuprofen were marginally protective, indomethacin in all doses accelerated mortality, and aspirin reduced mortality in a dose-response fashion. These results suggest that the protective effect of corticosteroids in radiation pneumonitis can be tentatively attributed to their anti-inflammatory actions, and that nonsteroidal anti-inflammatory agents, particularly those that affect lipoxygenase products, may offer equal or better protection than corticosteroids against mortality due to radiation pneumonitis.
- OSTI ID:
- 5074802
- Journal Information:
- Radiation Research; (United States), Journal Name: Radiation Research; (United States) Vol. 127:3; ISSN 0033-7587; ISSN RAREA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Protective effect of corticosteroids on radiation pneumonitis in mice
Attenuation of ozone-induced airway permeability in rats by pretreatment with cyclophosphamide, FPL 55712, and indomethacin
Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTIPYRETICS
ARACHIDONIC ACID
AZOLES
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYME INHIBITORS
HETEROCYCLIC COMPOUNDS
MAMMALS
METABOLISM
MICE
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PNEUMONITIS
RADIOINDUCTION
RADIOSENSITIVITY EFFECTS
RODENTS
TETRAZOLES
VERTEBRATES