Citation:

Snow, S., M. McGee, A. Henriquez, J. Richards, M. Schladweiler, A. Ledbetter, AND U. Kodavanti. Respiratory Effects and Systemic Stress Response Following Acute Acrolein Inhalation in Rats. Society of Toxicology, Baltimore, MD, March 12 - 16, 2017.

Impact/Purpose:

We have shown that exposure to ozone, a pulmonary irritant, causes myriad systemic metabolic and pulmonary effects that are attributed to neuronal and hypothalamus-pituitary-adrenal axis activation. In this study we show that, a nasal irritant acrolein, also produces some of the similar systemic effects while causing nasal irritation and injury, suggesting some differences in reflex neural regulation of these two air pollutants in how they mediate systemic and respiratory effects.

Description:

Previous studies have demonstrated that exposure to ozone, a pulmonary irritant, causes myriad systemic metabolic and pulmonary effects that are attributed to neuronal and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically-impaired models. In order to elucidate the systemic consequences and the contribution of the HPA axis in mediating metabolic and respiratory effects of acrolein, a sensory irritant, we examined pulmonary, nasal, and systemic effects in rats following exposure. Male, 10 week old Wistar and Goto Kakizaki (GK) rats, a non-obese type II diabetic Wistar-derived model, were exposed to 0, 2 or 4 ppm acrolein, 4h/day for 1 or 2 days. Acrolein exposure at 4 ppm significantly increased pulmonary and nasal damage in both strains as demonstrated by increased inspiratory and expiratory times indicating labored breathing, elevated biomarkers of injury, and neutrophilic inflammation. Overall, at both time points acrolein exposure caused noticeably more damage in the nasal passages as opposed to the lung with vascular protein leakage occurring only in the nose. Acrolein exposure (4 ppm) also led to metabolic impairment by inducing hyperglycemia and glucose intolerance (GK>Wistar) as indicated by glucose tolerance testing. In addition, serum total cholesterol (GKs only), LDL cholesterol (both strains), and free fatty acids (GK>Wistar) levels increased; however, no acrolein-induced changes were noted in branched-chain amino acid (BCAA) or insulin levels, which have previously been reported following ozone exposure. These responses corresponded with a significant increase in corticosterone and modest but insignificant increases in adrenaline, suggesting activation of the HPA axis. Collectively, these data demonstrate that acrolein exposure has a profound effect on nasal and pulmonary injury/inflammation, as well as glucose and lipid metabolism, with the systemic effects intensified in the metabolically-impaired GK rats. These results are similar to ozone-induced responses with exception of lung protein leakage and the ability to alter BCAA and insulin levels, suggesting some differences in reflex neural regulation of these two air pollutants. (This abstract does not reflect US EPA Policy).

Record Details: