Metabolism and elimination kinetics of mono ‐hydroxylated PAHs metabolites (OH‐PAHs) following single exposure to different combinations of PAH4 in rats

AbstractThe metabolism of polycyclic aromatic hydrocarbons (PAHs) and the elimination kinetics of their mono-hydroxylated metabolites (OH-PAHs) following single exposure to different combinations of four PAHs (PAH4) were studied. Male Sprague –Dawley rats were orally exposed to a single dose of benzo[a]pyrene (B[a]P) or PAH2 (B[a]P + chrysene), PAH3 (B[a]P + chrysene + benz[a]anthracene (B[a]A)) and PAH4 (B[a]P + chrysene + B[a]A + benzo[b]fluoranthene (B[b]F)) with each combination adjusted to the same dose of individual compound. OH- PAHs including 3-OHB[a]P, 3-hydroxychrysene (3-OHC), 3-OHB[a]A and 1-hydroxypyrene (1-OHP) were detected in serum and urine samples collected at 6 intervals over a 72-h period post-dosing. The hepatic mRNA levels of cytochrome P450 (CYPs) were determined to ascertain the expression induction of PAHs metabolic enzymes. Results showed OH-PAHs (except 1-OHP) peaked within 8 h in serum and were excreted from urine within 24-48 h. The serum and urinary concentration of 3-OHB[a]P was significantly increased after PAH4 exposure compared to other PAHs combinations. Inversely, urinary concentration of 3-OHC was decreased after PAH4 exposure. While the kinetics of 3-OHB[a]A or 1-OHP were not different depending on the PAHs combinations. Also, CYPs were markedly induced by PAHs. Notably, the induction levels of CYP1A1 and CYP1B1 were significantly higher after PAH4 exposure compared to B[a]P exposu re. The results indicated the metabolism of B[a]P was a...

Source: Journal of Applied Toxicology - May 16, 2023 Category: Toxicology Authors: Miao Yang, Kanmin Mao, Xin Cao, Hongjuan Liu, Xinzheng Wang, Weifeng Mao, Liping Hao Tags: RESEARCH ARTICLE Source Type: research