Inhibitory effect of hexachloro-p-xylene on hepatic drug-metabolizing enzymes in mice
Abstract
Our another experiment showed that the drug-metabolizing enzymes in rat liver could be induced by hexachloro-p-xylene (HCX), a clonorchicide similar to DDT in chemical structure, physicochemical properties and disposition in the body. In this study we found that HCX exerted an inhibitory effect on the drug-metabolizing enzymes in mouse liver.
A single dose of HCX (12.5-150 mg/ kg) ig to mice increased the duration of the hypnosis of sodium pentobarbital. The rate of biotransformation of pentobarbital in vivo was reduced in mice pretreated with HCX100 mg/kg, ig and the t1/2 β of pentobarbital in treated mice was 6.1 h, while that in control mice was 2.3 h.
The rate of biotransformation of sodium pentobarbital and aminopyrine in liver homogenates of mice pretreated with HCX 100 mg/kg ig was reduced significantly, but the cytochrome P-450 and cytochrome b5 contents unchanged.
HCX, either a single dose or multiple doses, showed inhibitory effect on hepatic drug-metabolizing enzymes in mice. In rats, however, a single dose of HCX did not affect the duration of the hypnosis of sodium pentobarbital significantly, but multiple doses reduced pentobarbital hypnotic time and exerted a stimulatory effect on hepatic drug-metabolizing enzymes.
These results indicated a species difference in the effect of HCX on hepatic drug-metabolizing enzymes.
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Keywords:
A single dose of HCX (12.5-150 mg/ kg) ig to mice increased the duration of the hypnosis of sodium pentobarbital. The rate of biotransformation of pentobarbital in vivo was reduced in mice pretreated with HCX100 mg/kg, ig and the t1/2 β of pentobarbital in treated mice was 6.1 h, while that in control mice was 2.3 h.
The rate of biotransformation of sodium pentobarbital and aminopyrine in liver homogenates of mice pretreated with HCX 100 mg/kg ig was reduced significantly, but the cytochrome P-450 and cytochrome b5 contents unchanged.
HCX, either a single dose or multiple doses, showed inhibitory effect on hepatic drug-metabolizing enzymes in mice. In rats, however, a single dose of HCX did not affect the duration of the hypnosis of sodium pentobarbital significantly, but multiple doses reduced pentobarbital hypnotic time and exerted a stimulatory effect on hepatic drug-metabolizing enzymes.
These results indicated a species difference in the effect of HCX on hepatic drug-metabolizing enzymes.
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