Metabolism and elimination kinetics of mono-hydroxylated PAHs metabolites following single exposure to different combinations of PAH4 in rats

The 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), and PAH4 (B[a]P + chrysene + B[a]A + benzo[b]fluoranthene) with each combination adjusted to the same dose of individual compound. OH-PAHs including 3-hydroxybenzo[a]pyrene, 3-hydroxychrysene, 3-hydroxybenz[a]anthracene, and 1-hydroxypyrene (1-OHP) were detected in serum and urine samples collected at six 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-hydroxybenzo[a]pyrene was significantly increased after PAH4 exposure compared with other PAHs combinations. Inversely, urinary concentration of 3-hydroxychrysene was decreased after PAH4 exposure, and the kinetics of 3-hydroxybenz[a]anthracene 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 with B[a]P exposure. The results indicated the metabolism of B[a]P was accelerated after PAH4 exposure which might be partly due to the induction of CYPs. These results confirmed PAHs are rapidly metabolized and suggested potential interactions of PAHs may happen among PAH4 mixture.

Automated summary

The metabolism and elimination kinetics of polycyclic aromatic hydrocarbons (PAHs) and their mono-hydroxylated metabolites (OH-PAHs) were studied after single exposure to different combinations of PAHs (PAH4). Serum and urine samples were collected at six intervals over 72 hours post-dosing to detect OH-PAHs. The mRNA levels of cytochrome P450 (CYPs) were determined to assess the expression induction of PAH metabolic enzymes. Results showed that PAH4 exposure led to increased serum and urinary levels of 3-hydroxybenzo[a]pyrene, decreased urinary levels of 3-hydroxychrysene, and had no effect on the kinetics of 3-hydroxybenz[a]anthracene or 1-hydroxypyrene. PAH4 exposure also significantly induced the expression of CYP1A1 and CYP1B1. These findings suggest that the metabolism of benzo[a]pyrene is accelerated after PAH4 exposure, possibly due to the induction of CYPs. The results also indicate potential interactions among PAHs in PAH4 mixtures.