Diallyl trisulfide attenuated n-hexane induced neurotoxicity in rats by modulating P450 enzymes

•DATS pretreatment attenuated n-hexane induced peripheral neuropathy in rat.•DATS changed the metabolic profiling of n-hexanes.•DATS suppressed the bioactivation of n-hexane via modulating P450 enzymes.

Chronic exposure to n-hexane can induce serious nerve system impairments without effective preventive medicines. Diallyl trisulfide (DATS) is a garlic-derived organosulfur compound, which has been demonstrated to have many beneficial effects. The current study was designed to evaluate whether DATS could restrain n-hexane induced neurotoxicity in rats and to explore the underlying mechanisms. Rats were treated with n-hexane (3 g/kg, p.o.) and different doses of DATS (10, 20 and 30 mg/kg, p.o.) for 8 weeks. Behavioral assessment showed that DATS could inhibit n-hexane induced neurotoxicity, demonstrated by the improvement of the grip strength and decline of gait scores. Toxicokinetic analysis revealed that the Cmax and AUC0-t of 2,5-hexanedione (product of n-hexane metabolic activation) and 2,5-hexanedione protein adducts in serum were significantly declined in DATS-treated rats, and the levels of pyrrole adducts in tissues were significantly reduced. Furthermore, DATS activated CYP1A1 and inhibited n-hexane induced increased expression and activity of CYP2E1 and CYP2B1. Collectively, these findings indicated that DATS protected the rats from n-hexane-induced neurotoxicity, which might be attributed to the modulation of P450 enzymes by DATS.