Further studies on the in vivo effect of diisopropyl 1,3-dithiol-2-ylidenemalonate (NKK-105) on the liver microsomal drug oxidation system in rats

Katoh, Minoru; Kitada, Munehiro; Satoh, Tetsuo; Kitagawa, Haruo; Sugimoto, Tatsuyoshi; Kasai, Tamotsu

doi:10.1016/0006-2952(81)90412-3

Cited by 24 publications

(8 citation statements)

References 28 publications

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“…On the other hand, the effect of malotilate, which is considered a new type of inducer (13,14), on 7-alkoxycoumarin 0-dealkylase activities was clearly different from that of any other inducer examined in these experiments. Therefore, malotilate may have affected the population of P-450 species, and there might be a possibility that malotilate induced a form(s) of P-450 that is different from any of the already known species.…”

Section: Discussioncontrasting

confidence: 63%

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Comparison of the effects of various inducers on 7-alkoxycoumarin O-dealkylase activities in liver microsomes.

et al. 1989

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Abstract-The effects of six inducers and malotilate on 7-alkoxycoumarin 0 dealkylase activities in rat liver microsomes were examined. Phenobarbital (PB) (100 mg/kg) was administered intraperitoneally to rats for 6 days; 3-methylcholan threne (3-MC) (40 mg/kg), e9-naphthoflavone ((3-NF) (40 mg/kg), isosafrole (150 mg/kg) and polychlorinated biphenyls (PCB) (100 mg/kg) were administered intraperitoneally for 3 days; isoniazid (INH) (50 mg/kg) was administered intra peritoneally for 10 days; and malotilate (500 mg/kg) was administered orally for 3 days. The 0-dealkylase activities toward 7-methoxycoumarin (7-MC), 7 ethoxycoumarin (7-EC) and 7-propoxycoumarin (7-PC) were examined 24 hr after the final administration of the drugs. The ratios of 7-EC 0-deethylase and 7 PC 0-depropylase to 7-MC 0-demethylase activity in the control and six inducer treated groups were compared. The ratios in the groups treated with the six com pounds, each of which induces a different form(s) of cytochrome P-450 (P-450), were clearly different from each other. Therefore, the measurement of 7-alkoxy coumarin 0-dealkylase activities should be extremely useful for the routine deter mination of the molecular species of P-450. On the other hand, the ratio in the malotilate-treated group was different from that in any other inducer-treated group, so that there might be a possibility that malotilate induced a form(s) of P-450 that is different from any of the already known species.

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Section: Discussioncontrasting

confidence: 63%

“…We also measured these 0-dealkylase activities in rats treated with malotilate, a new type of inducer (13,14), and compared them with those in the groups treated with the other six induces.…”

Section: Many Hydrophobicmentioning

confidence: 99%

Comparison of the effects of various inducers on 7-alkoxycoumarin O-dealkylase activities in liver microsomes.

et al. 1989

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“…Katoh et al (11) demonstrated that malotilate charac teristically increased the content of b5 and the activity of NADPH-cytochrome c reductase rather than the content of P-450 in rat liver microsomes. They also reported that p-nitroanisole 0-demethylase activity and N-demethylase activities toward amino pyrine, benzphetamine and ethylmorphine were enhanced, but aniline hydroxylase activity was reduced by malotilate adminis tration (12). Recently, Kawata et al (13) showed similar results.…”

Section: Diisopropylmentioning

confidence: 78%

“…The effect of malotilate on the activities of aniline hydroxylase, aminopyrine N-demethylase, benzo(a)pyrene (B(a)P) hydroxylase and 7-ethoxycoumarin (7-EC) 0-deethylase per nmol cytochrome P-450. (10)(11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

Effect of malotilate (diisopropyl 1,3-dithiol-2-ylidenemalonate) on drug metabolizing activity in rat liver microsomes.

et al. 1987

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Abstract-The effect of malotilate (diisopropyl 1,3-dithiol-2-ylidenemalonate) on drug metabolizing activity in rat liver microsomes was examined. Malotilte (500 mg/kg/day) was administered orally to rats for 3 days. The contents of cyto chrome P-450 (P-450) and cytochrome b5 (b5), the activity of NADPH-cytochrome c reductase, and the metabolization of aniline, aminopyrine, benzo(a)pyrene (B(a)P) and 7-ethoxycoumarin (7-EC) in the microsomal fraction were examined 24 hr after the final administration of malotilate. The content of b5 and the activity of NADPH-cytochrome c reductase were increased by the malotilate treatment, but the content of P-450 was not significantly affected. 7-EC 0-deethylation was markedly and aminopyrine N-demethylation was moderately enhanced; in contrast, aniline hydroxylation was significantly and B(a)P hydroxylation was slightly reduced. Such different effects of malotilate among the four substrate-me tabolizing activities may be due mainly to the increase in the content of b5, which participates in the transport of the second electron required for P-450 function to various extents. It is also possible that malotilate affects the population of P-450 subtypes, each having a different substrate specificity and a different affinity for b5.

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“…Malotilate is known to induce the microsomal electron transport system in rat liver, especially cytochrome b5 and NADPH-cytochrome c reductase (2,3). These enzymes are also induced by the administration of other xenobiotics (4-6).…”

mentioning

confidence: 99%

Effect of malotilate (diisopropyl 1,3-dithiol-2-ylidenemalonate) on the protein synthesis in rat liver.

et al. 1982

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Further studies on the in vivo effect of diisopropyl 1,3-dithiol-2-ylidenemalonate (NKK-105) on the liver microsomal drug oxidation system in rats

Cited by 24 publications

References 28 publications

Comparison of the effects of various inducers on 7-alkoxycoumarin O-dealkylase activities in liver microsomes.

Comparison of the effects of various inducers on 7-alkoxycoumarin O-dealkylase activities in liver microsomes.

Effect of malotilate (diisopropyl 1,3-dithiol-2-ylidenemalonate) on drug metabolizing activity in rat liver microsomes.

Effect of malotilate (diisopropyl 1,3-dithiol-2-ylidenemalonate) on the protein synthesis in rat liver.

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