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

Okuno, Hiroyasu; Murase, Toshihiko; Nakanishi, Sadao; Shiozaki, Yasuko; Sameshima, Yoshiko

doi:10.1254/jjp.44.303

Cited by 3 publications

(2 citation statements)

References 26 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: 59%

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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: 59%

“…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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The anti-fibrogenic effect of a pharmaceutical composition of [5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione] (Oltipraz) and Dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate (DDB)

Kang

Kim

et al. 2002

Arch Pharm Res

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Liver fibrosis is a prepathological state wherein damaged liver tissues in chronic liver diseases, such as hepatitis, are not repaired to normal tissues, but converted to fibrous tissue. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a cancer chemopreventive agent, is effective against a wide variety of chemical carcinogens. Recently, we reported that oltipraz inhibits liver fibrogenesis (Kang et al., 2002). In the present study, the effects of oltipraz in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) on dimethylnitrosamine (DMN)-induced liver fibrogenesis were assessed in rats. Oltipraz (30 mg/kg body weight, p.o., 3 times per week for 4 weeks) was found to inhibit the increases in plasma ALT, AST and bilirubin by DMN, whereas DDB (30 mg/kg body weight, p.o., 3 times per week for 4 weeks) attenuated the increases in the plasma ALT and bilirubin. The lowered plasma protein and albumin contents in DMN-treated rats were completely restored by oltipraz, but not by DDB. DDB decreases liver cell injury and inflammation through inhibition of nuclear factor-kB. DMN increased the accumulation of liver collagen, as indicated by the increase in the 4-hydroxyproline content in liver homogenates, which was reduced by treatment with oltipraz, but not by DDB. Given the differential effect between oltipraz and DDB, the potential enhancement of antifibrotic efficacy by the drugs was assessed in the animal model. Despite the minimal effect of DDB on DMN-induced fibrogenesis, DDB (5-25 mg/kg), administered together with oltipraz (25-5 mg/kg), showed an additive protective effect against hepatotoxicity and fibrosis induced by DMN, which was shown by the blood chemistry parameters and histopathological analysis. The adequate composition ratio of oltipraz to DDB was 5:1. These results provide information on the pharmaceutical composition, comprising of oltipraz and DDB as the active components, for the treatment and/or prevention of liver fibrosis and cirrhosis.

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Comparison of the Effects of Various Inducers on 7-Alkoxycoumarin O-Dealkylase Activities in Liver Microsomes

Okuno¹,

Nakanishi²,

Kitao³

et al. 1989

Japanese Journal of Pharmacology

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

Cited by 3 publications

References 26 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.

The anti-fibrogenic effect of a pharmaceutical composition of [5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione] (Oltipraz) and Dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate (DDB)

Comparison of the Effects of Various Inducers on 7-Alkoxycoumarin O-Dealkylase Activities in Liver Microsomes

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