Hepatic drug-metabolizing enzyme activity in rats pretreated with (−)-emetine or (±)-2,3-dehydroemetine

1. Pretreatment of female rats with (−)-emetine or (±)-2,3-dehydroemetine (at 18μmol/kg body wt. for 24h) prolongs the hexobarbital-induced sleeping-time of the treated animals. 2. This effect is not observed on pretreating animals with other compounds closely related to (−)-emetine, such as (−)-isoemetine or (+)-O-methylpsychotrine. 3. Liver microsomal drug-metabolizing enzyme activity in vitro as measured by N-demethylation of aminopyrine and azo-reduction of Neoprontosil is inhibited in rats pretreated with (−)-emetine or with (±)-2,3-dehydroemetine. 4. These inhibitory effects on drug metabolism in vitro are not observed in corresponding experiments involving pretreatment of rats with (−)-isoemetine or (+)-O-methylpsychotrine. 5. Co-administration of emetine or 2,3-dehydroemetine and sodium phenobarbital or 1,1-dichloro-2-o-chlorophenyl-2-p-chlorophenylethane to rats abolishes or greatly diminishes the stimulation of drug-metabolizing enzyme activity in vitro usually obtained by the administration of phenobarbital or 1,1-dichloro-2-o-chlorophenyl-2-p-chlorophenylethane alone. 6. Further, in rats pretreated with sodium phenobarbital and subsequently injected with emetine or 2,3-dehydroemetine the pre-stimulated drug-metabolizing enzyme activity in vitro is diminished. 7. The inhibitory effects on drug-metabolizing enzyme activity after pretreatment with (−)-emetine or (±)-2,3-dehydroemetine do not appear to be related to NADPH generation.

Download Full-text

Effect of hexachlorophene, tribromsalan, trichlorcarban and cloflucarban on hexobarbital sleeping time and hepatic drug-metabolizing enzyme activity in vitro in the rat

Biochemical Pharmacology ◽

10.1016/0006-2952(79)90101-1 ◽

1979 ◽

Vol 28 (3) ◽

pp. 375-380 ◽

Cited By ~ 4

Author(s):

Lyman W. Condie ◽

Donald R. Buhler

Keyword(s):

Enzyme Activity ◽

Hepatic Drug ◽

Sleeping Time ◽

Drug Metabolizing Enzyme ◽

Hexobarbital Sleeping Time ◽

Metabolizing Enzyme

Download Full-text

Effect of Splenectomy on the Activity of Drug-Metabolizing Enzymes in the Liver of Rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y71-022 ◽

1971 ◽

Vol 49 (3) ◽

pp. 161-166 ◽

Cited By ~ 7

Author(s):

Jules Brodeur ◽

Claude Marchand

Keyword(s):

Indirect Evidence ◽

Female Rats ◽

Microsomal Enzymes ◽

Drug Metabolizing Enzyme ◽

Effect Of Splenectomy ◽

Maximal Induction ◽

Metabolizing Enzyme ◽

Cytochrome P 450 ◽

Liver Microsomal Enzymes

Splenectomy was performed in adult female rats in order to investigate the influence of removal of the spleen on liver microsomal enzymes and cytochrome P-450 in vitro, as well as on the pharmacological activity of certain drugs in intact animals. Splenectomy significantly decreases the amount of cytochrome P-450 at 1 and 4 days after the operation, but not at 7 days. The activity of the enzymes catalyzing the metabolism of parathion, p-nitroanisole, and zoxazolamine is also decreased 4 days after splenectomy, whereas that of the enzymes involved in the metabolism of hexobarbital is unchanged. The maximal induction by phenobarbital of the enzymatic activities catalyzing the metabolism of parathion, p-nitroanisole, and zoxazolamine is prevented by splenectomy. Splenectomy exerts very little effect on plasma levels of hexobarbital and hexobarbital sleeping time; however, in both control and phenobarbital-pretreated rats, splenectomy results in a marked increase in the duration of zoxazolamine paralysis. These results indicate that splenectomy exerts inhibitory effects on certain liver microsomal enzymes, and provide some indirect evidence in support of the view that the hepatic blood supply is important for maintaining normal levels of drug-metabolizing enzyme activity in the liver.

Download Full-text