Susceptibility to Inhaled Flame-Generated Ultrafine Soot in Neonatal and Adult Rat Lungs

Abstract

Over a quarter of the U.S. population is exposed to harmful levels of airborne particulate matter (PM) pollution, which has been linked to development and exacerbation of respiratory diseases leading to morbidity and mortality, especially in susceptible populations. Young children are especially susceptible to PM and can experience altered anatomic, physiologic, and biological responses. Current studies of ambient PM are confounded by the complex mixture of soot, metals, allergens, and organics present in the complex mixture as well as seasonal and temporal variance. We have developed a laboratory-based PM devoid of metals and allergens that can be replicated to study health effects of specific PM components in animal models. We exposed 7-day-old postnatal and adult rats to a single 6-h exposure of fuel-rich ultrafine premixed flame particles (PFPs) or filtered air. These particles are high in polycyclic aromatic hydrocarbons content. Pulmonary cytotoxicity, gene, and protein expression were evaluated at 2 and 24 h postexposure. Neonates were more susceptible to PFP, exhibiting increased lactate dehydrogenase activity in bronchoalveolar lavage fluid and ethidium homodimer-1 cellular staining in the lung in situ as an index of cytotoxicity. Basal gene expression between neonates and adults differed for a significant number of antioxidant, oxidative stress, and proliferation genes and was further altered by PFP exposure. PFP diminishes proliferation marker PCNA gene and protein expression in neonates but not adults. We conclude that neonates have an impaired ability to respond to environmental exposures that increases lung cytotoxicity and results in enhanced susceptibility to PFP, which may lead to abnormal airway growth.

Age-Specific Effects on Rat Lung Glutathione and Antioxidant Enzymes after Inhaling Ultrafine Soot

“…PFPs were burner generated (17,18) at a mass concentration of 22.4 6 5.6 mg/m 3 PFP (mean 6 SD) with a mean particle size of 70.6 nm 6 1.5. Particles were high in organic carbon with an lelemental carbon:organic carbon ratio of 0.58.…”

“…Eight-weekold male adult rats and newborn postnatal male Sprague Dawley rats with dams (Harlan Laboratories, Indianapolis, IN) were acclimated in filtered air (FA) for 5 to 7 days before use as previously described (17,18). Animals were necropsied at 2, 24, and 48 hours after cessation of the 6-hour exposure to FA or PFP.…”

“…The variable nature of ambient PM complicates the systematic study of health effects, so we have developed and characterized a premixed flame particle (PFP)-generating system (17,18) for in vivo chamber inhalation exposure studies. Ethylene flame-generated PFPs are 70-nm ultrafine particles rich in PAHs that are also present in the vapor phase.…”

“…In the current study, we exposed male, 7-day-old neonatal pups and 8-week-old young adult rats to a single acute inhalation exposure to PFPs and collected samples at various times up to 48 hours after exposure. We have previously shown that neonates have enhanced susceptibility to PFPs compared with adult rats (18). To further investigate possible mechanisms responsible for the enhanced cytotoxicity, we analyzed GSH levels as well as biosynthesis and conjugating enzymes related to the glutathione pathway ( Figure 1).…”

Water Electrified Sprays for Emission Control in Energy Production Processes

“…[7][8][9][10][11][12][13]). Among them, the International Agency for Research on Cancer (IARC) classified soot particles as a human mutagen and carcinogenic substance [14].…”