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Sex and strain modify antioxidant response to early life ozone exposure in rats.
Gibbs-Flournoy, E., J. Richards, E. Hines, K. Kraft, J. Norwood, G. Hatch, AND J. Dye. Sex and strain modify antioxidant response to early life ozone exposure in rats. VCRS Symposium on Respiration in Health and Disease, E. Lansing, MI, September 18 - 21, 2016.
To better understand susceptibility to oxidant pollutants and its potential to contribute to chronic obstructive pulmonary disease-like change, this study was designed to determine: (1) whether rat strain differences observed in adults were apparent early in life, and (2) whether sex differences in baseline antioxidant levels or antioxidant responsiveness to ozone existed.
In the US, chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death. In women, its impact continues to increase. Oxidant insults like cigarette smoke and air pollution, especially during critical periods of early life, appear to further increase risk of COPD through-out the life course. We previously showed that upon exposure to the oxidant pollutant, ozone (O3), lung injury/inflammation in adult (90d) male (♂) rats of the Fisher344 (F344) strain was significantly less than Wistar (WIS) or Sprague-Dawley (SD) rats. However, to date, toxicology studies of chronic, near-lifelong O3 exposure have mainly utilized adult ♂ F344 rats. To better understand susceptibility to oxidant pollutants and its potential to contribute to COPD-like change, this study was designed to determine: (1) whether rat strain differences observed in adults were apparent early in life, and (2) whether sex differences in baseline antioxidant levels or antioxidant responsiveness to O3 existed. First, lung antioxidant and related enzyme levels were determined in neonatal WIS rats immediately post-exposure to air or O3 (1 ppm x 2h) in 14d (pre-weaning), 21d (at weaning), or 28 d (post-weaning) pups. Results showed that lung antioxidants and enzymes (expressed per gm of wet lung weight) increased with maturity, especially post-weaning. Very immature females (♀) appeared to be the least protected. Next, levels in WIS, SD and F344 pups exposed at 14 or 21d to air or O3 (0.5 or 1 ppm x 2h) were compared. F344 pups were notably smaller and reduced litter size of F344 dams necessitated uneven pup group sizes. Negligible sex differences in body weight or lung antioxidant levels were observed in air controls within strains, however strain comparisons revealed that 14d F344 pups had 6-22% more total GSH than SD or W pups. GSH decreased in all strains from 14-21d. Lung superoxide dismutase (SOD) also decreased from 14-21d in all strains, however levels in F344 pups were 25-35% higher than SD or W. Post-O3, 14d ♀ pups of all strains had minor GSH decrements (20%); while levels in ♂ pups were unchanged. The 14d SD and W ♀ pups also had decreases in GSH peroxidase, GSH reductase, SOD, and uric acid; while levels in ♀ F344 pups were unchanged or increased. The 14d ♂ pups showed minimal changes in these parameters. Conversely, post-O3 the 21d ♀ pups showed minimal change while SD and W ♂ pups had increased SOD; and ♂ SD pups had increased GSH peroxidase/reductase. Together these data suggest that like the adult rats, F344 pups are generally more resistant to oxidant insult; while neonatal ♀ SD and W pups are more susceptible than ♂ pups of the same age and strain. Studies are needed to establish the health consequences of reduced early life lung antioxidant responses in the context of repeated or chronic exposure to urban oxidant air pollutants. (Abstract does not reflect USEPA policy).