title: The effects of acute hydrogen sulfide poisoning on cytochrome P450 isoforms activity in rats.
abstract: Hydrogen sulfide (H2S) is the second leading cause of toxin related death (after carbon monoxide) in the workplace. H2S is absorbed by the upper respiratory tract mucosa, and it causes histotoxic hypoxemia and respiratory depression. Cocktail method was used to evaluate the influences of acute H2S poisoning on the activities of cytochrome P450 isoforms CYP2B6, CYP2D6, CYP3A4, CYP1A2, CYP2C19, and CYP2C9, which were reflected by the changes of pharmacokinetic parameters of six specific probe drugs, bupropion, metoprolol, midazolam, phenacetin, omeprazole, and tolbutamide, respectively. The experimental rats were randomly divided into two groups, control group and acute H2S poisoning group (inhaling 300 ppm for 2 h). The mixture of six probes was given to rats by oral administration and the blood samples were obtained at a series of time points through the caudal vein. The concentrations of probe drugs in rat plasma were measured by LC-MS. The results for acute H2S poisoning and control groups were as follows: there was a statistically significant difference in the AUC and C max for bupropion, metoprolol, phenacetin, and tolbutamide, while there was no statistical pharmacokinetic difference for midazolam and omeprazole. Acute H2S poisoning could inhibit the activity of CYP2B6, CYP2D6, CYP1A2, and CYP2C9 in rats.
authors.affiliation: Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Xianqin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Mengchun
authors.initials: M
authors.lastname: Chen
authors.affiliation: Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Jianshe
authors.initials: J
authors.lastname: Ma
authors.affiliation: Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Wen
authors.affiliation: Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Pan
authors.affiliation: The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Lufeng
authors.initials: L
authors.lastname: Hu
authors.affiliation: The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Guanyang
authors.initials: G
authors.lastname: Lin
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000506:poisoning*; D006862:Hydrogen Sulfide / Q000506:poisoning*; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010599:Pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D006862:Hydrogen Sulfide