dicumarol has been researched along with 1-naphthol* in 2 studies
2 other study(ies) available for dicumarol and 1-naphthol
| Article | Year |
|---|---|
Mechanisms of toxic injury to isolated hepatocytes by 1-naphthol.
The mechanism(s) of toxicity of 1-naphthol and two of its possible metabolites, 1,2- and 1,4-naphthoquinone, to freshly isolated rat hepatocytes has been studied. 1-Naphthol and both naphthoquinones exhibited a dose-dependent toxicity to hepatocytes. [1-14C]-1-Naphthol was metabolised by hepatocytes predominantly to its glucuronic acid and sulphate ester conjugates, but small amounts of covalently bound products were also formed. Blebbing on the surface of the hepatocytes was observed following exposure to 1-naphthol and the naphthoquinones, together with a dose-dependent decrease in intracellular glutathione (GSH), which preceded the onset of cytotoxicity. The toxicity of 1-naphthol and the naphthoquinones was potentiated by dicoumarol, an inhibitor of DT-diaphorase (NAD(P)H:quinone oxidoreductase). This enhanced toxicity was accompanied by a greater amount of surface blebbing, an increased depletion of intracellular GSH, particularly in the case of 1-naphthol and 1,4-naphthoquinone, and a decreased metabolism of 1-naphthol to its conjugates with variable effects on the amount of covalently bound products formed. These results support the suggestion that the toxicity of 1-naphthol may be mediated by the formation of 1,2-naphthoquinone and/or 1,4-naphthoquinone, which may then be metabolised by one electron reduction to naphthosemiquinone radicals. These, in turn, may covalently bind to important cellular macromolecules or enter a redox cycle with molecular oxygen thereby generating active oxygen species. Both of these processes appear to play a role in producing the cytotoxic effects of 1-naphthol. Topics: Animals; Dicumarol; Glutathione; In Vitro Techniques; Liver; Male; Naphthols; Naphthoquinones; Rats; Rats, Inbred Strains | 1984 |
Generation of low-level chemiluminescence during the metabolism of 1-naphthol by rat liver microsomes.
The metabolism of 1-naphthol in rat liver microsomal fractions supplemented with NADPH is accompanied by low-level chemiluminescence which reflects the formation of molecular excited states. Photoemission consists of two phases which both are dependent on microsomal protein and 1-naphthol concentration. The involvement of cytochrome P-450 in the microsomal metabolism of 1-naphthol was indicated by an inhibition of chemiluminescence by aminopyrine or metyrapone. Oxygen is required for light emission. Whereas phase I is hardly influenced by superoxide dismutase, phase II is suppressed. Chemiluminescence was not associated with malondialdehyde accumulation, in contrast to NADPH-dependent lipid peroxidation in microsomal fractions in the absence of 1-naphthol. Phase I of chemiluminescence appears to directly reflect cytochrome P-450-dependent hydroxylation, and phase II is attributed to redox cycling of products arising from these reactions, e.g. the 1,4- and/or 1,2-naphthoquinones as oxidation products of the corresponding dihydroxynaphthalenes. Topics: Aminopyrine; Animals; Dicumarol; In Vitro Techniques; Luminescent Measurements; Malondialdehyde; Metyrapone; Microsomes, Liver; Naphthols; Oxygen Consumption; Quinone Reductases; Rats | 1984 |