The Effects of H(2)S on the Activities of CYP2B6, CYP2D6, CYP3A4, CYP2C19 and CYP2C9 in Vivo in Rat

Hydrogen sulfide (H(2)S) is a colorless, flammable, extremely hazardous gas with a “rotten egg” smell. The human body produces small amounts of H(2)S and uses it as a signaling molecule. The cocktail method was used to evaluate the influence of H(2)S 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 H(2)S group. The H(2)S 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 H(2)S 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. H(2)S could not influence the activities of CYP2B6, CYP2D6 and CYP2C19 in rats, while H(2)S could induce the activity of CYP3A4 and inhibit the activity of CYP2C9 in rats.