ABSTRACT
OBJECTIVE:To study the effects of Tibetan medicine Zuotai on the activities of cytochrome oxidase (CYP1A2) and drug metabolism enzyme N-acetyltransferase 2(NAT2)in rats. METHODS:70 SD rats were equally randomized into a normal control (normal saline) group,the groups of single administration of low,middle and high-dose (1.2,3.8 and 12 mg/kg) Zuotai and the groups of multiple administrations thereof(once daily for 12 consecutive days). The rats were given drugs ig. caffeine(25 mg/kg)was given ig to the rats in the normal control group and the groups of single administration on the 2nd day,and to those in the groups of multiple administrations on the 13th day. 5 h later,their urine was collected and added with vitamin C based on 10 mg/ml. High performance liquid chromatography (HPLC) was adopted to determine the cafeine metabolites contents of 5-acetami-do-6-formamido-3-methyl-uric acid(AFMU),1-methylxanthine(1X),1-methyl-uric acid(1U)and 1,7-dimethyl uric acid(17U) in rats’urine,and the activities of CYP1A2 and NAT2 were reflected through (AFMU+1X+1U)/17U and AFMU/(AFMU+1X+1U). RESULTS:Compared with normal control group,the(AFMU+1X+1U)/17U and AFMU/(AFMU+1X+1U)in rats were de-creased,namely the activities of CYP1A2 and NAT2 were lower in the groups of single administration of middle-dose Zuotai and multiple administrations of middle and high-dose Zuotai than in the normal control group. There was statistical difference (P<0.05). CONCLUSIONS:Zuotai can obviously inhibit the activities of CYP1A2 and NAT2 in rats.
ABSTRACT
To study the effect of Tibetan medicine Zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2, three different doses (1.2, 3.8 and 12 mg x kg(-1)) of Zuotai were administrated orally to rats once a day or once daily for twelve days, separately. Rats were administrated orally caffeine (CF) on the second day after Zuotai administration, and the urine concentration of CF metabolite 5-acetylamino-6-formylamino-3-methyl-uracil (AFMU), 1-methyluric acid (1U), 1-methylxanthine (1X), 1, 7-dimethylxanthine (17U) at 5 h after study drug administration was determined by RP-HPLC. The activity of CYP1A2 and NAT2 was evaluated by the ratio of metabolites (AFMU+1X+1U)/17U and the ratio of AFMU/(AFMU+1X+1U), respectively. The protein and mRNA expression of CYP1A2 and NAT2 were determined by ELISA and RT-PCR method, respectively. After single administration of Zuotai 3.8 mg x kg(-1) and repeated administration of Zuotai 3.8 and 12 mg x kg(-1), the activity of CYP1A2 and NAT2 decreased significantly compared with control group and there was no significant difference between other dose group and control group. The protein expression of CYP1A2 was significant lower than that in control group after repeated administration of Zuotai 12 mg x kg(-1), and the mRNA expression of CYP1A2 decreased significantly compared with that of control group after single administration of Zuotai 3.8 mg x kg(-1) and repeated admistration of Zuotai 12 mg x kg(-1), separately. The protein expression of NAT2 decreased significantly compared with that of control group after single and repeated administration of Zuotai 3.8 mg x kg(-1), respectively, and the mRNA expression of CYP1A2 decreased significantly compared with control group after single administration of Zuotai 3.8 mg x kg(-1). This study found that Tibetan medicine Zuotai had significant effect on the activity, protein and mRNA expression of CYP1A2 and NAT2.