ISOLATED PERFUSED LIVER TECHNOLOGY FOR STUDYING METABOLIC AND TOXICOLOGICAL PROBLEMS

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Abstract
The isolated perfused liver system is a versatile model for investigating the effects and mechanisms of action of hepatotoxins and the metabolism of endogenous and exogenous compounds. The interpretation of metabolic data and apparent toxic events is dependent upon the viability and reproducibility of the model. In this study, a new approach has been undertaken to assess the viability of isolated liver preparations. This has involved the continuous monitoring of multistage processes namely, the synthesis and secretion of radiolabelled proteins, glycoproteins and lipoproteins on the one hand and the uptake of macromolecules by receptor-mediated endocytosis on the other. The consistency of these complex integrated processes from one liver to another and in particular the steady-state rate of production of radiolabelled macromolecules over 6h perfusion periods suggests that this model can be used with confidence for metabolic/toxicological investigations. The selectivity of the responses to chemical challenge(s) shows that this system can be exploited for (a) screening potential hepatotoxins; (b) identifying areas of metabolism which are affected and (c) advancing basic knowledge of liver biochemistry.