title: The effects of H2S on the activities of CYP2B6, CYP2D6, CYP3A4, CYP2C19 and CYP2C9 in vivo in rat.
abstract: Hydrogen sulfide (H2S) is a colorless, flammable, extremely hazardous gas with a "rotten egg" smell. The human body produces small amounts of H2S and uses it as a signaling molecule. The cocktail method was used to evaluate the influence of H2S on the activities of CYP450 in rats, which were reflected by the changes of pharmacokinetic parameters of five specific probe drugs: bupropion, metroprolol, midazolam, omeprazole and tolbutamide, respectively. The rats were randomly divided into two groups, control group and H2S group. The H2S group rats were given 5 mg/kg NaHS by oral administration once a day for seven days. The mixture of five probes was given to rats through 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. In comparing the H2S group with the control group, there was a statistically pharmacokinetics difference for midazolam and tolbutamide; the area under the plasma concentration-time curve (AUC) was decreased for midazolam (p < 0.05) and increased for tolbutamide (p < 0.05); while there was no statistical pharmacokinetics difference for bupropion, metroprolol and omeprazole. H2S could not influence the activities of CYP2B6, CYP2D6 and CYP2C19 in rats, while H2S could induce the activity of CYP3A4 and inhibit the activity of CYP2C9 in rats.
authors: Xianqin
authors: X
authors: Wang
authors: Anyue
authors: A
authors: Han
authors: Congcong
authors: C
authors: Wen
authors: Mengchun
authors: M
authors: Chen
authors: Xinxin
authors: X
authors: Chen
authors: Xuezhi
authors: X
authors: Yang
authors: Jianshe
authors: J
authors: Ma
authors: Analytical and Testing Center, Wenzhou Medical University, Wenzhou 325035, China. guanyanglinwzmc@gmail.com.
authors: Guanyang
authors: G
authors: Lin
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D016642:Bupropion / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D065702:Cytochrome P-450 CYP2B6; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006207:Half-Life; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D013058:Mass Spectrometry; D008874:Midazolam / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D009853:Omeprazole / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004791:Enzyme Inhibitors; D016642:Bupropion; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; C507848:CYP2C9 protein, rat; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; C465260:Cyp3a2 protein, rat; D065702:Cytochrome P-450 CYP2B6; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D009853:Omeprazole; D008874:Midazolam; D006862:Hydrogen Sulfide