Coculture of rabbit liver and myocardial slices: Potentiation of the cardiotoxicity of allyl alcohol but not allylamine

The coculture of precision-cut rabbit liver and myocardial slices as a tool to investigate metabolite-mediated cardiotoxicity was examined by determining the effect of metabolic activation on the cardiotoxicity of allylamine (AAM) and allyl alcohol (AOH). AAM is activated by benzylamine oxidase, a predominantly cardiovascular enzyme, to acrolein. Acrolein is also produced from AOH by alcohol dehydrogenase, which is primarily found in the liver. Under suitable conditions, the coculture of liver and myocardial slices had no detrimental effect on the viability of either tissue type, as assessed by protein synthesis. AAM and AOH (10^-7 and 10^-5 M) were not significantly toxic to liver slices. AAM, but not AOH, was toxic to myocardial slices in organ culture. In coculture, 10^-5 M AOH was significantly toxic in comparison to both control myocardial slices and myocardial slices exposed to the same concentration of AOH without the presence of liver slices. These results indicate that the coculture of liver and myocardial slices is a viable approach to the in vitro study of metabolism-mediated toxicity in the heart.