Combustion-derived flame generated ultrafine soot generates reactive oxygen species and activates Nrf2 antioxidants differently in neonatal and adult rat lungs

Jackie K W Chan, Jessica G. Charrier, Sean D. Kodani, Christoph F. Vogel, Sarah Y. Kado, Donald S. Anderson, Cort Anastasio, Laura S. Van Winkle

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Background: Urban particulate matter (PM) has been epidemiologically correlated with multiple cardiopulmonary morbidities and mortalities, in sensitive populations. Children exposed to PM are more likely to develop respiratory infections and asthma. Although PM originates from natural and anthropogenic sources, vehicle exhaust rich in polycyclic aromatic hydrocarbons (PAH) can be a dominant contributor to the PM2.5 and PM0.1 fractions and has been implicated in the generation of reactive oxygen species (ROS).ObjectivesCurrent studies of ambient PM are confounded by the variable nature of PM, so we utilized a previously characterized ethylene-combusted premixed flame particles (PFP) with consistent and reproducible physiochemical properties and 1) measured the oxidative potential of PFP compared to ambient PM, 2) determined the ability of PFPs to generate oxidative stress and activate the transcription factor using in vitro and ex vivo models, and 3) we correlated these responses with antioxidant enzyme expression in vivo. Methods: We compared oxidative stress response (HMOX1) and antioxidant enzyme (SOD1, SOD2, CAT, and PRDX6) expression in vivo by performing a time-course study in 7-day old neonatal and young adult rats exposed to a single 6-hour exposure to 22.4 mug/m3 PFPs. Results: We showed that PFP is a potent ROS generator that induces oxidative stress and activates Nrf2. Induction of the oxidative stress responsive enzyme HMOX1 in vitro was mediated through Nrf2 activation and was variably upregulated in both ages. Furthermore, antioxidant enzyme expression had age and lung compartment variations post exposure. Of particular interest was SOD1, which had mRNA and protein upregulation in adult parenchyma, but lacked a similar response in neonates. Conclusions: We conclude that PFPs are effective ROS generators, comparable to urban ambient PM2.5, that induce oxidative stress in neonatal and adult rat lungs. PFPs upregulate a select set of antioxidant enzymes in young adult animals, yet are unaffected in neonates. We conclude that the inability of neonatal animals to upregulate the antioxidant response may, in part, explain enhanced their susceptibility to ultrafine particles, such as PFP.

Original languageEnglish (US)
Pages (from-to)34
Number of pages1
JournalParticle and Fibre Toxicology
DOIs
StateAccepted/In press - Aug 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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    Chan, J. K. W., Charrier, J. G., Kodani, S. D., Vogel, C. F., Kado, S. Y., Anderson, D. S., Anastasio, C., & Van Winkle, L. S. (Accepted/In press). Combustion-derived flame generated ultrafine soot generates reactive oxygen species and activates Nrf2 antioxidants differently in neonatal and adult rat lungs. Particle and Fibre Toxicology, 34. https://doi.org/10.1186/1743-8977-10-34