Age-dependent effect of ozone on pulmonary eicosanoid metabolism in rabbits and rats
- New York Univ. Medical Center, New York (USA)
Acute exposures to ozone have previously been shown to cause quantitative changes in the spectrum of arachidonic acid (AA) metabolites in lung lavage fluid. Since age appears to be an important variable in the toxicity of inhaled ozone, we investigated its effect on ozone-induced changes in pulmonary eicosanoid metabolism. Rats and rabbits ranging in age from neonates to young adults were exposed either to air or to 1 ppm ozone for 2 hr. Lung lavage fluid was collected within 1 hr following exposure and analyzed for its content of selected eicosanoids. In both species, there was a pronounced effect of age on ozone-induced pulmonary eicosanoid metabolism. Ozone-exposed animals at the youngest ages examined had severalfold greater amounts of two products of the cyclooxygenase pathway, prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha), than did age-matched controls. This effect lessened and eventually disappeared as the animals grew toward adulthood. In rabbits, ozone also induced increases in 6-keto-prostaglandin F1 alpha and thromboxane B2, but these changes were of lesser magnitude and evident only in the youngest rabbits exposed. There was no observed effect of ozone on lung lavage content of leukothriene B4. Indices of nonspecific pulmonary damage, i.e., protein concentration in lung lavage fluid and total number and viability of lavaged lung cells, were affected by ozone exposure, but not in an age-dependent manner that correlated with changes in pulmonary eicosanoid metabolism. In vitro ozone exposure of lung macrophages from naive rabbits of the same age range as those exposed in vivo demonstrated that ozone is capable of stimulating the elaboration of PGF2 alpha and especially PGE2. However, the increase in lavage fluid PGE2 and PGF2 alpha caused by ozone inhalation could not be attributed to macrophage metabolism conclusively.
- OSTI ID:
- 5799236
- Journal Information:
- Fundamental and Applied Toxicology; (USA), Vol. 15:4; ISSN 0272-0590
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
EICOSANOIC ACID
METABOLISM
LUNGS
SENSITIVITY
OZONE
BIOLOGICAL EFFECTS
ACUTE EXPOSURE
AGE DEPENDENCE
ARACHIDONIC ACID
BIOLOGICAL PATHWAYS
INHALATION
LAVAGE
MACROPHAGES
OXYGENASES
PROSTAGLANDINS
PROTEINS
RABBITS
RATS
ANIMAL CELLS
ANIMALS
BODY
CARBOXYLIC ACIDS
CONNECTIVE TISSUE CELLS
ENZYMES
INTAKE
MAMMALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PHAGOCYTES
RESPIRATORY SYSTEM
RODENTS
SOMATIC CELLS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology