Trout liver slices for metabolism and toxicity studies.
Aquatic species are increasingly used in metabolism and toxicity studies, both from the perspective of potential for chemical exposure and usefulness as nonmammalian model systems. In the present study, trout liver slices were compared with freshly isolated trout hepatocytes with regard to metabolic capabilities and biochemical indices of cell health. Liver slices were also used to discern toxicant-induced changes in liver cell histology. Levels of ATP and glutathione were similar between liver slice and isolated hepatocyte preparations. The cytochrome P450-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 protein in isolated cells. 7-Ethoxycoumarin metabolism was also comparable between preparations (1.36 vs. 1.22 nmol/min/mg protein). For conjugative metabolism, glucuronidation of 7-hydroxycoumarin or 1-naphthol did not differ in the two in vitro systems. However, neither slices nor isolated hepatocytes sulfated 7-hydroxycoumarin, whereas 1-naphthylsulfate 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 hepatotoxicants 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 levels were unchanged. Histopathological damage was seen in slices incubated for 24 hr with either toxicant, but was most pronounced with allyl alcohol. These data indicate that liver slices are an excellent in vitro model for metabolism and toxicity studies in aquatic species.
Singh, Y; Cooke, JB; Hinton, DE; Miller, MG
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