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

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

Published In Am J Respir Cell Mol Biol, (2013 Jan)

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 metabolism and 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/m(3) 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.

PubMed ID: 23065132 Exiting the NIEHS site

MeSH Terms: Administration, Inhalation; Age Factors; Animals; Animals, Newborn; Antioxidants/metabolism*; Gene Expression Regulation, Developmental/drug effects; Gene Expression Regulation, Enzymologic/drug effects; Glutamate-Cysteine Ligase/genetics; Glutamate-Cysteine Ligase/metabolism; Glutathione Disulfide/metabolism; Glutathione Peroxidase/genetics; Glutathione Peroxidase/metabolism; Glutathione Reductase/genetics; Glutathione Reductase/metabolism; Glutathione Transferase/genetics; Glutathione Transferase/metabolism; Glutathione/metabolism*; Humans; Lung/drug effects*; Lung/growth & development; Lung/metabolism*; Male; Oxidative Stress/drug effects; Particulate Matter/administration & dosage; Particulate Matter/toxicity*; RNA, Messenger/genetics; RNA, Messenger/metabolism; Rats; Rats, Sprague-Dawley; Vehicle Emissions/toxicity

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