TROUT LIVER SLICES FOR METABOLISM AND TOXICITY STUDIES

Aquatic species are increasingly used in metabolism and toxicity studi es, both from the perspective of potential for chemical exposure and u sefulness as nonmammalian model systems. In the present study, trout l iver slices were compared with freshly isolated trout hepatocytes with regard to metabolic capabilities and biochemical indices of cell heal th. Liver slices were also used to discern toxicant-induced changes in liver cell histology. Levels of ATP and glutathione were similar betw een liver slice and isolated hepatocyte preparations. The cytochrome P 450-dependent rate of formation of biphenyl metabolites was 0.48 +/- 0 .04 nmol/min/mg protein in slices and 0.43 +/- 0.06 nmol/min/mg protei n in isolated cells. 7-Ethoxycoumarin metabolism was also comparable b etween preparations (1.36 vs. 1.22 nmol/min/mg protein). For conjugati ve metabolism, glucuronidation of 7-hydroxycoumarin or 1-naphthol did not differ in the two in vitro systems. However, neither slices nor is olated hepatocytes sulfated 7-hydroxycoumarin, whereas 1-naphthylsulfa te represented as much as 20% of total 1-naphthol metabolites in both preparations. Histological evaluation of control liver slices after a 24-hr incubation indicated only minor changes, Response to the hepatot oxicants allyl formate and allyl alcohol was evaluated in slices only. Both compounds, after a 4-hr treatment and at concentrations between 0.1 and 1.0 mM, caused extensive depletion of glutathione, but ATP lev els were unchanged. Histopathological damage was seen in slices incuba ted for 24 hr with either toxicant, but was most pronounced with allyl alcohol. These data indicate that liver slices are an excellent in vi tro model for metabolism and toxicity studies in aquatic species.