Evaluation of protective effects of Chi-Zhi-Huang decoction on Phase I drug metabolism of liver injured rats by cocktail probe drugs.
OBJECTIVE
Chi-Zhi-Huang decoction (PGR) is one of the traditional Chinese medicine (TCM) preparations with unique effect on withdrawing jaundice and has been used to treat icteric patients in China for many years. In this research, we aim at to evaluate the potential activity of PGR in restoring hepatic drug metabolism in a damaged liver.


METHODS
A cocktail approach with caffeine (10mg/kg), dapsone (10mg/kg) and chlorzoxazone (20mg/kg) respectively as probe drug of cytochrome P450 (CYP) isoform of CYP 1A2, 3A4 and 2E1 was used to evaluate its possible effects on Phase I oxidative metabolism. Pretreated with three dosages of PGR water extract (0.75, 1.5 and 3g/kg, po) for 5 days, male Wistar rats (220-240 g) were intoxicated by phenylisothiocyanate (PITC, 100mg/kg, po) 24h before probes intravenous injection. The pharmacokinetics of the probes in the blood was determined simultaneously by HPLC, and their non-compartmental parameters were used to evaluate the metabolic difference among the groups. Moreover, the levels of liver enzymes (ALT, AST, ALP) and bilirubins were also measured for insight of liver function.


RESULTS
The findings in this study suggest that PGR induces CYP 3A4, does not have much effect on CYP 2E1, and inhibits CYP 1A2 at high dosage.


CONCLUSIONS
The current pharmacokinetic approach allowed the protective effects of PGR on oxidative drug metabolism in damaged liver to be systemically examined and will certainly help in the explanation of synergistic effect of the composites formula.
Tang
Hao
H
Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China.
Min
Guangtao
G
Ge
Bin
B
Li
Yumin
Y
Liu
Xia
X
Jiang
Shengxiang
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000378:metabolism; D002110:Caffeine / Q000493:pharmacokinetics / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002753:Chlorzoxazone / Q000493:pharmacokinetics / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D003622:Dapsone / Q000493:pharmacokinetics / Q000633:toxicity; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D010946:Plants, Medicinal / Q000737:chemistry; D020011:Protective Agents; D051381:Rats; D017208:Rats, Wistar
D004365:Drugs, Chinese Herbal; D020011:Protective Agents; C532051:chi-zhi-huang; D002110:Caffeine; D003622:Dapsone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002753:Chlorzoxazone; D001663:Bilirubin