Age-specific effects on rat lung glutathione and antioxidant enzymes after inhaling ultrafine soot

Jackie K W Chan, Sean D. Kodani, Jessie G. Charrier, Dexter Morin, Patricia C. Edwards, Donald S. Anderson, Cort Anastasio, Laura S. Van Winkle

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Vehicle exhaust is rich in polycyclic aromatic hydrocarbons (PAHs) and is a dominant contributor to urban particulate pollution (PM). Exposure to PM is linked to respiratory and cardiovascular morbidity and mortality in susceptible populations, such as children. PM can contribute to the development and exacerbation of asthma, and this is thought to occur because of the presence of electrophiles in PM or through electrophile generation via the metabolism of PAHs. Glutathione (GSH), an abundant intracellular antioxidant, confers cytoprotection through conjugation of electrophiles and reduction of reactive oxygen species. GSH-dependent phase II detoxifying enzymes glutathione peroxidase and glutathione S-transferase facilitate metabolismand conjugation, respectively. Ambient particulates are highly variable in composition, which complicates systematic study. In response, we have developed a replicable ultrafine premixed flame particle (PFP)-generating system for in vivo studies. To determine particle effects in the developing lung, 7-day-old neonatal and adult rats inhaled 22 μg/m3 PFP during a single 6-hour exposure. Pulmonary GSH and related phase II detoxifying gene and protein expression were evaluated 2, 24, and 48 hours after exposure. Neonates exhibited significant depletion of GSH despite higher initial baseline levels of GSH. Furthermore, we observed attenuated induction of phase II enzymes (glutamate cysteine ligase, glutathione reductase, glutathione S-transferase, and glutathione peroxidase) in neonates compared with adult rats. We conclude that developing neonates have a limited ability to deviate from their normal developmental pattern that precludes adequate adaptation to environmental pollutants, which results in enhanced cytotoxicity from inhaled PM.

Original languageEnglish (US)
Pages (from-to)114-124
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume48
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • Glutathione peroxidase
  • Glutathione S-transferases
  • Lung development
  • Oxidative stress
  • Ultrafine particulate matter

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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    Chan, J. K. W., Kodani, S. D., Charrier, J. G., Morin, D., Edwards, P. C., Anderson, D. S., Anastasio, C., & Van Winkle, L. S. (2013). Age-specific effects on rat lung glutathione and antioxidant enzymes after inhaling ultrafine soot. American Journal of Respiratory Cell and Molecular Biology, 48(1), 114-124. https://doi.org/10.1165/rcmb.2012-0108OC