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Acrolein inhalation variably impacts neuroendocrine axes and serum metabolic profiles of male and female rats
Citation:
Alewel, D., T. Jackson, A. Henriquez, S. Vance, Mette C. Schladweiler, S. Gavett, A. Fisher, R. Grindstaff, P. Evansky, AND U. Kodavanti. Acrolein inhalation variably impacts neuroendocrine axes and serum metabolic profiles of male and female rats. NC Society of Toxicology Annual Meeting, Durham, NC, October 19, 2022.
Impact/Purpose:
Metabolomic analysis of both sexes revealed increased lipolysis, muscle protein catabolism, and shifts in mitochondrial respiration markers associated with changes in steroid metabolism and sympathetic stress activity in males but not in females.
Description:
Anthropogenic and wildfire smoke emissions are strongly linked with the development of metabolic syndromes, including diabetes and dyslipidemia. A major constituent of these emissions, acrolein, is known to induce adverse cardiopulmonary effects, and thus is on EPA’s priory list of hazardous air pollutants. However, the ability for acrolein to induce systemic neuroendocrine and metabolic derangement has not been systematically investigated. Moreover, few health effects studies address potential sexually dimorphic responses to inhaled stressors. Here, 12-week-old male and female Wistar-Kyoto rats underwent acrolein nose-only inhalation in incremental concentrations (0, 0.1, 0.316, 1ppm) for 30 min (for assessment of ventilatory changes), followed by a 3.5hr exposure at 3.16ppm (n=8/group). We assessed nasal and pulmonary lavages (NALF and BALF), circulating pituitary and adrenal hormones, and other hallmarks of peripheral stress from samples collected immediately post exposure. We further performed serum metabolic profiling, analyzing circulating biomolecules. Acrolein induced potent nasal but not pulmonary injury and vascular leakage (increased NALF total protein, albumin, and LDH activity) in both males and females. However, the inflammatory response was apparent in both nasal and pulmonary airways but only in males. Acrolein increased plasma corticosterone only in males, also displaying glucocorticoid-like effects of lymphopenia and hyperglycemia. Further, serum pituitary hormone levels of triiodothyronine, prolactin, and testosterone were greatly diminished in acrolein-exposed males. Metabolomic analysis of both sexes revealed increased lipolysis, muscle protein catabolism, and shifts in mitochondrial respiration markers associated with changes in steroid metabolism and sympathetic stress activity in males but not in females. In conclusion, acrolein induces neuroendocrine stress reactions that are linked to changes in circulating metabolites reflective of alterations in metabolic processes within liver, adipose, and muscle tissue. Moreover, males show increased susceptibility to global metabolic derangement, which may have implications for sex-specific risk for metabolic diseases (Does not reflect US EPA policy).