Science Inventory

Systemic Metabolic Impairment and Lung Injury Following Acrolein Inhalation

Citation:

Kodavanti, U., M. Schladweiler, A. Ledbetter, M. McGee, J. Richards, D. Andrews, D. Miller, A. Henriquez, AND S. Snow. Systemic Metabolic Impairment and Lung Injury Following Acrolein Inhalation. Society of Toxicology Meeting, New Orleans, LA, March 13 - 17, 2016.

Impact/Purpose:

Acrolein is an irritant air pollutant. Even though we know that ozone induces metabolic impairment that is exacerbated in diabetic rats, it is not known if acrolein will produce similar effects. These data suggest that although lung inflammatory effects of acrolein might be suppressed in diabetic rats, these rats will have greater metabolic impairment from acrolein exposure. And that acrolein, like ozone, can produce systemic metabolic alterations in diabetic rats.

Description:

A single ozone exposure causes pulmonary injury and systemic metabolic alterations through neuronal and hypothalamus pituitary adrenal axis activation. Metabolically impaired Goto Kakizaki (GK) rats with non-obese type-2 diabetes are more sensitive to ozone induced changes than healthy rats. In order to understand how acrolein, an upper airway sensory irritant, might produce differential systemic and pulmonary responses than the response produced by ozone, a deep lung irritant, we exposed healthy male Wistar and GK rats (18 week-old) to air or acrolein. In the first experiment, rats were exposed to air or 2ppm acrolein, 4h/day for 2 days and in the second experiment rats were exposed to air or 3ppm acrolein x 4h/day for 1 day. Pulmonary ventilatory parameters, injury, inflammation as well as systemic changes in glucose tolerance, circulating lipids, metabolic markers and stress hormones were assessed. Baseline blood glucose, stress hormones and pulmonary LDH as well as protein leakage were higher, but insulin levels were lower in GK relative to Wistar rats. Acrolein at 2ppm concentration did not change systemic or pulmonary injury/inflammation outcomes. However, 3ppm acrolein exacerbated hyperglycemia and glucose intolerance in GK rats. Acrolein exposure also increased serum triglycerides but only in GK rats. Acrolein exposure at 3 ppm did not produce pulmonary protein leakage but increased -glutamyl transferase activity in lavage fluid in both strains, indicating airway cell injury. Acrolein (3ppm) caused neutrophilic inflammation but only in Wistar rats. Interestingly, acrolein also induced eosinophilic lung inflammation in both strains (Wistar>GK). Collectively, these data suggest that although lung inflammatory effects of acrolein might be suppressed in diabetic rats, these rats will have greater metabolic impairment from acrolein exposure. And that acrolein, like ozone, can produce systemic metabolic alterations in diabetic rats. (This abstract does not reflect EPA Policy).

Record Details:

Record Type:DOCUMENT( PRESENTATION/ ABSTRACT)
Product Published Date:03/17/2016
Record Last Revised:03/30/2016
OMB Category:Other
Record ID: 311615