Sex-specific respiratory and systemic endocrine effects of acute acrolein and trichloroethylene inhalation
Acrolein and trichloroethylene (TCE) are considered priority hazardous air pollutants due to associations with cardiopulmonary health effects; however, acute neuroendocrine stress-related systemic reactions are not fully characterized. Employing acrolein, a potent airway irritant, and TCE, with low irritancy, we hypothesized that airway injury and inflammation would be involved in eliciting neuroendocrine-mediated systemic alterations. Male and female Wistar-Kyoto rats were exposed nose-only to air, acrolein or TCE in incremental concentrations over 30 min, followed by 3.5-hr exposure to the highest concentration (acrolein - 0.0, 0.1, 0.316, 1, 3.16 ppm; TCE - 0.0, 3.16, 10, 31.6, 100 ppm) while performing head-out plethysmography (HOP), and animals were necropsied immediately post-exposure. HOP revealed TCE reduced tidal volume while acrolein decreased minute volume and increased inspiratory time and PenH in a concentration-dependent manner (males>females). Acrolein, but not TCE, inhalation led to significant increases in nasal-lavage fluid (NALF) protein and lactate-dehydrogenase activity, as well as inflammatory cell influx and higher IL-6 levels (males ≥ females). However, neither acrolein nor TCE increased bronchoalveolar-lavage fluid (BALF) injury markers, although BALF macrophages and neutrophils were increased in acrolein-exposed males and females. Females had higher baseline plasma corticosterone and lower circulating lymphocytes compared to males. Acrolein increased circulating adrenocorticotrophic hormone and consequently corticosterone and caused lymphopenia, but only in males. Acrolein-induced systemic changes were also associated with reduced circulating thyroid-stimulating hormone, prolactin, and testosterone in males. In conclusion, males were more sensitive to acrolein-induced nasal injury and inflammation, but both sexes showed modest lung-inflammation response. TCE did not induce acute respiratory irritancy effects. Acrolein-induced changes were associated with sex-specific systemic neuroendocrine alterations linked to hypothalamic-pituitary-adrenal and sympathetic-adrenal-medullary axes activation.