Effects of coadministration of berberine chloride with cyclosporin on liver microsomal cytochrome P450 isoenzyme and mdr1 in rats
- VernacularTitle:盐酸小檗碱与环孢素A合用对大鼠肝P450同工酶和mdr1的影响
- Author:
Huawen XIN
;
Xiaochun WU
;
Qing LI
;
Airong YU
;
Mingyuan ZHONG
;
Min ZHU
;
Youying LIU
;
- Publication Type:Journal Article
- Keywords:
berberine chloride;
cyclosporin;
cytochrome P450;
multidrug resistance gene
- From:
Chinese Pharmacological Bulletin
1986;0(04):-
- CountryChina
- Language:Chinese
-
Abstract:
AIM To study the effects of coadministration of berberine chloride(Ber) with cyclosporin (CsA) on liver microsomal cytochrome P450 isoenzyme and multi drug resistance gene in rats. METHODS The activities of liver microsomal erythromycin demethylase(ERD) and aminopyrence N demethylase(ADM) were determined. The levels of mRNA expression of CYP3A1, CYP1A1, CYP2E1, mdr1a and mdr1b were assayed with RT PCR. RESULTS After administration for 6 days, all treatment groups except Ber at 100 mg?kg -1 exhibited inhibitory action on ERD activity in rats. ERD activity markedly decreased in all drug treatment groups after taking drug for 12 days. After administration for 6 days, 45 mg?kg -1 CsA, 100 mg?kg -1 Ber coadministrated with 45 mg?kg -1 CsA and 200 mg?kg -1 Ber plus 45 mg?kg -1 CsA had significant inhibitory effects on ADM activity in rats. All groups except 100 mg?kg -1 Ber and 150 mg?kg -1 ketoconazole had the same effects on ADM activity after treatment for 12 days. Again, after 12 days, all drug treatment groups except 100 mg?kg -1 Ber group was found of remarkable inhibition of the mRNA expression of CYP3A1, CYP2E1, mdr1a and mdr1b. The CYP1A1 gene was not detected in all groups. CONCLUSION The mechanism of Ber to increase CsA concentration is that Ber decreases the expression of CYP3A, mdr1a and mdr1b thereby reduces the metabolism and elimination of CsA by liver.
