Inhibition of lipopolysaccharide-induced liver injury in rats treated with a hepatic drug-metabolizing enzyme inducer p,p′-DDT

Phenobarbitone (PB) (75 mg/kg) was administered orally for three consecutive days to pregnant or lactating rats at different pre- and postnatal stages in order that the perinatal animals would receive the agent either by transplacental passage or via the milk. Control animals received equivalent volumes of saline. The dams, fetuses, and pups were killed 24 h after the last dose. Hepatic p-nitroanisole O-demethylase (OD), carboxylesterase (CE), and bromosulfophthalein–glutathione (BSP–GSH) conjugating enzyme activities in a 12 100 g – 20 min supernatant of a 20% w/v homogenate were measured. The morphology of the developing rat liver in the absence and presence of PB was examined by electron microscopy.The results demonstrated that the transplacental passage of PB to rat fetuses at term or 3 days prepartum had no effect on either the hepatic drug-metabolizing enzyme activities or on the ultrastructural appearance of the liver. Increased hepatic OD activity was observed in the pregnant animal but no effect was observed in the lactating dam. Phenobarbitone received by the suckling rat had two distinct effects. Compared to control activities, twofold increases in hepatic OD activity were observed in rat pups as early as 4 days after birth, associated with a marked proliferation in hepatic smooth endoplasmic reticulum. In contrast, PB-related significant increases in neonatal hepatic CE and BSP–GSH conjugating enzyme activities were not observed until 21 days of age. In the 4-day-old treated pups, characteristic morphological changes included numerous small membrane whorls in addition to increased smooth endoplasmic reticulum and microbodies in the liver.

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Bioavailability of the diterpenoid 14-deoxy-11,12-didehydroandrographolide in rats and up-regulation of hepatic drug-metabolizing enzyme and drug transporter expression

Phytomedicine ◽

10.1016/j.phymed.2019.152841 ◽

2019 ◽

Vol 61 ◽

pp. 152841 ◽

Cited By ~ 3

Author(s):

Chih-Ching Yen ◽

Yun-Ta Liu ◽

Ying-Jyan Lin ◽

Ya-Chen Yang ◽

Chien-Chih Chen ◽

...

Keyword(s):

Drug Transporter ◽

Hepatic Drug ◽

Drug Metabolizing Enzyme ◽

Metabolizing Enzyme ◽

Transporter Expression

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TIME COURSE OF INDUCTION OF RAT HEPATIC DRUG METABOLIZING ENZYME ACTIVITIES FOLLOWING DIETARY ADMINISTRATION OF FLAVONOIDS

Journal of Toxicology and Environmental Health ◽

10.1080/009841096160709 ◽

1996 ◽

Vol 49 (5) ◽

pp. 481-496 ◽

Cited By ~ 23

Author(s):

Marie H l ne Siess Jean Philippe Ma

Keyword(s):

Enzyme Activities ◽

Time Course ◽

Hepatic Drug ◽

Drug Metabolizing Enzyme ◽

Metabolizing Enzyme

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Studies on Metabolism and Disposition of Sizofiran (SPG), an Anti-tumor Polysaccharide. II. Effects on Hepatic Drug-Metabolizing Enzyme System in Rats

YAKUGAKU ZASSHI ◽

10.1248/yakushi1947.110.2_159 ◽

1990 ◽

Vol 110 (2) ◽

pp. 159-162

Author(s):

Shohji TANJI ◽

Kazuo AKIMA ◽

Minoru YOSHIOKA ◽

Kazuo NOMURA ◽

Masahiro HORIBA ◽

...

Keyword(s):

Enzyme System ◽

Hepatic Drug ◽

Drug Metabolizing Enzyme ◽

Metabolizing Enzyme

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

Biochemical Journal ◽

10.1042/bj1170491 ◽

1970 ◽

Vol 117 (3) ◽

pp. 491-498 ◽

Cited By ~ 10

Author(s):

H. H. Miller ◽

R. K. Johnson ◽

J. D. Donahue ◽

W. R. Jondorf

Keyword(s):

Enzyme Activity ◽

Female Rats ◽

Inhibitory Effects ◽

Hepatic Drug ◽

Azo Reduction ◽

Drug Metabolizing Enzyme ◽

Metabolizing Enzyme ◽

Sodium Phenobarbital ◽

Stimulation Of

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.

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