Acrolein-induced transcriptomic alterations in male Wistar-Kyoto rats

Acute acrolein inhalation in male rats resulted in multi-tissue transcriptomic alterations that were observed through Illumina mRNA sequencing. Specifically, site-specific respiratory expression profile differences were noted between air- and acrolein-exposed groups. Nasal epithelial tissue demonstrated 452 differentially expressed genes (DEGs) (310 up-regulated and 142 down-regulated)and lung tissue demonstrated 95 DEGs (80 up-regulated and 15 down-regulated). Notable transcriptomic alterations were also observed in liver tissue of acrolein-exposed rats, with 1699 identified DEGs (788 up-regulated and 911 down-regulated). A variety of mRNA expression profile differences resulting from acute acrolein inhalation was observed in other peripheral tissues, including adipose, muscle, adrenals, hippocamus, and hypothalamus. Gene changes were largely representative of oxidative and inflammatory response in the nose, as well as xenobiotic metabolism changes in the lung. Liver changes, which were most numerous, included alterated metabolic signaling (Sirtuin and FXR signaling), as well as alterated oxidoreductive, GPCR, and glucocorticoid pathways. Together, these data demonstrate acrolein, a well-characterized respiratory irritant, induces systemic neuroendocrine immunological and metabolic stress. Adult male Wistar-Kyoto rats were exposed to air (0ppm) or acrolein nose-only for 4hr total exposure duration. For the first 30 minutes of exposure, increasing half-log exposure concentrations were used at 0, 0.1, 0.316, and 1 ppm, such that each concentration was employed for 7.5 minutes, with this 30 minute window being followed by 3.5 hours at the highest concentration of acrolein of 3.16 ppm. Exposures were conducted ~0700-1100 AM and performed under general room temperature and humidity. Immediately after exposure, rats were necropsied, tissues collected and flash frozen in liquid nitrogen, and frozen for later analysis. Later, RNA was extracted and sequenced.