The Effects of H2S on the Activities of CYP2B6, CYP2D6, CYP3A4, CYP2C19 and CYP2C9 in Vivo in Rat

Xianqin Wang,Jianshe Ma,Xinxin Chen,Congcong Wen,Anyue Han,Guanyang Lin,Xuezhi Yang,Mengchun Chen

doi:10.3390/ijms141224055

Xianqin Wang, Jianshe Ma + Show 6 more

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https://doi.org/10.3390/ijms141224055

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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.

Highlights

H2S is a natural decaying product of organic matter, which is highly toxic as a result of environmental and industrial exposure [1]
H2S could not influence the activities of CYP450 isoforms CYP2B6, CYP2D6, CYP2C19 in vivo in rats, while H2S could induce the activity of CYP3A4 and inhibit the activity of
H2S could not influence the activities of CYP450 isoforms CYP2B6, CYP2D6, CYP2C19 in vivo in rats, while H2S could induce the activity of CYP3A4 and inhibit the activity of CYP2C9 in vivo in rats

Summary

Introduction

H2S is a natural decaying product of organic matter, which is highly toxic as a result of environmental and industrial exposure [1]. The results from an increasing number of studies are reporting that H2S is produced endogenously in various parts of the body and that H2S is involved in many physiological functions in mammals, especially in the nervous system and cardiovascular system [2,3,4]. H2S has been referred to as the third gaseous signaling molecule alongside nitric oxide (NO) and carbon monoxide (CO) [2,5,6]. It is involved in the relaxation of smooth muscle and as a vasodilator [7] and is active in the brain, where it increases the response of the NMDA receptor and facilitates long term potentiation [8].

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