Comparison of the toxicity of allyl alcohol, coumarin and menadione in precision-cut rat, guinea-pig, Cynomolgus monkey and human liver slices
Archives of Toxicology(1996)
摘要
The toxicity of allyl alcohol, coumarin and menadione has been studied in precision-cut liver slice cultures. Liver slices
were prepared from male Sprague- Dawley rats, male Dunkin-Hartley guinea-pigs and from samples of Cynomolgus monkey and human
liver using a Krumdieck tissue slicer. The liver slices were cultured with the test compounds for 24h in a dynamic organ culture
system. Toxicity was assessed by measurement of protein synthesis, potassium content and the MTT assay. At the concentrations
examined, menadione produced marked toxicity in liver slices from all four species, whereas rat liver slices were less susceptible
to allyl alcohol toxicity. Coumarin produced concentration-dependent toxic effects in rat and guinea-pig liver slices, whereas
Cynomolgus monkey and human liver slices were relatively resistant, especially at low coumarin concentrations. At some concentrations
of the test compounds examined, the MTT assay appeared to be a less sensitive indicator of toxicity than either protein synthesis
or potassium content. These results demonstrate the usefulness of precision-cut liver slices for assessing species differences
in xenobiotic-induced toxicity.
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关键词
Key words Allyl alcohol,Coumarin,In vitro toxicity,Menadione,Precision-cut liver slices
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