title: Diallyl trisulfide attenuated n-hexane induced neurotoxicity in rats by modulating P450 enzymes.
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 Cmaxand AUC0-tof 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.
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Xujing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Xianjie
authors.initials: X
authors.lastname: Li
authors.affiliation: Jinan Municipal Center for Disease Control & Prevention, Jinan, Shandong Province, China.
authors.forename: Hongyin
authors.initials: H
authors.lastname: Yin
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Han
authors.affiliation: North East Regional Health Authority, Ocho Rios, Jamaica.
authors.forename: Gleniece
authors.initials: G
authors.lastname: Irving
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zeng
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong 250012, China. Electronic address: keqinx@sdu.edu.cn.
authors.forename: Keqin
authors.initials: K
authors.lastname: Xie
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006586:Hexanes / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D000498:Allyl Compounds; D006586:Hexanes; D013440:Sulfides; C042577:diallyl trisulfide; C026385:n-hexane; D003577:Cytochrome P-450 Enzyme System
keywords: 2,5-Hexanedione; CYP450; Diallyl trisulfide; Neurotoxicology; Pyrrole adducts; n-Hexane