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Chem Biol Interact. 2017 Mar 1;265:1-7. doi: 10.1016/j.cbi.2017.01.013. Epub 2017 Jan 20.

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

Author information

1
Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong 250012, China.
2
Jinan Municipal Center for Disease Control & Prevention, Jinan, Shandong Province, China.
3
North East Regional Health Authority, Ocho Rios, Jamaica.
4
Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong 250012, China. Electronic address: keqinx@sdu.edu.cn.

Abstract

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.

KEYWORDS:

2,5-Hexanedione; CYP450; Diallyl trisulfide; Neurotoxicology; Pyrrole adducts; n-Hexane

PMID:
28115069
DOI:
10.1016/j.cbi.2017.01.013
[Indexed for MEDLINE]

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