Citation:

Dye, J., E. Gibbs-Flournoy, J. Richards, J. Norwood, K. Kraft, AND G. Hatch. Neonatal rat age, sex and strain modify acute antioxidant response to ozone. INHALATION TOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, 29(7):291-303, (2017). https://doi.org/10.1080/08958378.2017.1369602

Impact/Purpose:

Early life exposure to an adverse environment during critical or sensitive periods of respiratory and immune development may increase risk of developing chronic diseases of various organ systems, including respiratory conditions, throughout the life course. The present pilot study examined several factors in both male and female neonatal rat pups of the F344, SD, and WIS strains to assess: (A) if rat strain (i.e., genetics), sex, or stage of early life development affected baseline lung antioxidant and redox-related enzyme levels; and (B) if any of these factors modulated antioxidant responsiveness to early life ozone exposure.

Description:

Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death in the U.S. and its impact continues to increase in women. Oxidant insults during critical periods of early life appear to increase risk of COPD through-out the life course. To better understand susceptibility to early life exposure to oxidant air pollutants we used Fisher (F344), Sprague- Dawley (SD), and Wistar (WIS) male and female neonatal rat pups to assess: (A) if strain (i.e., genetics), sex, or stage of early life development affected baseline lung antioxidant or redox enzyme levels; and (B) if these same factors modulated antioxidant responsiveness to acute ozone exposure (1 ppm x 2h) on post-natal day (PND) 14, 21, or 28. In air-exposed pups from PND14-28, some parameters were unchanged (e.g., uric acid), some decreased (e.g., superoxide dismutase), while others increased (e.g., glutathione recycling enzymes) especially postweaning. Lung total glutathione levels decreased in F344 and SD pups, but were relatively unchanged in WIS pups. Post-ozone exposure, data suggest that: (1) the youngest (PND14) pups were the most adversely affected; (2) neonatal SD and WIS pups, especially females, were more prone to ozone effects than males of the same age; and (3) F344 neonates (females and males) were less susceptible to oxidative lung insult, not unlike F344 adults. Differences in antioxidant levels and responsiveness between sexes and strains and at different periods of development may provide a basis for assessing later life health outcomes - with implications for humans with analogous genetic or dietary-based lung antioxidant deficits.

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