Neonatal rat age, sex and strain modify acute antioxidant response to ozone

Abstract

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the US 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 × 2 h) 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 post-weaning. 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.

Keywords:

• Antioxidants
• lung
• neonatal rats
• ozone

Acknowledgements

The authors thank Dr. Daniel Costa, Kay Crissman, Dr. Robert Devlin, Richard Jaskot, Dr. Michael Madden and Ralph Slade for their expertise and assistance in planning or performing these studies. We thank John McKee and inhalation facility personnel for conducting the ozone exposures. We express our thanks to Dr. Erin Hines and Dr. Michael Madden for a critical review of this report.

Disclosure statement

This manuscript has been reviewed by the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency and approved for publication. Approval does not signify that contents necessarily reflect the views and policies of the agency, nor does the mention of trade names of commercial products constitute endorsement for use.