Abstract
Liver Slice Technology is a relatively new addition to the battery of in vitro assays of xenobiotic metabolism and toxicity evaluation. As with any developing technology, evaluation and refinement of the technique will be an essential component of its implementation to routine use. Three goals of this article will be to: (1) provide a brief survey of currently used methods for immediate and cultured liver slices, (2) review the use of liver slices in the assessment and quantification of pharmacological and toxicological responses, and (3) discuss the possible use of Liver Slice Technology for the investigation of drug interactions.
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Ekins, S., Williams, A., Murray, G. I., Burke, M. D., Marchant, N. C., Engeset, J., and Hawksworth, G. M. (1996) Xenobiotic metabolism in rat dog, and human precision-cut liver slices, freshly isolated hepatocytes and vitrified precision-cut liver slices. Drug Metab. Dispos. 24, 990–995.
Sidelmann, U. G., Cornett, J., Tornelund, J., and Hansen, S. H. (1996) A compara tive study of precision cut liver slices, hepatocytes and microsomes from wistar rat using metronidazole as a model susbtrate. Xenobiotica 26, 709–722.
Carlile, D. J., Katayoun, Z., and Houston, B. J. (1997) Scaling factors to relate drug metabolic clearance in hepatic microsomes, isolated heptocytes and the intact liver: Studies with induced livers using Diazepam. Drug Metab. Dispos. 25, 903–911.
Ruegg, C. E., Gandolfi, A. J., Nagle, R. B., and Brendel, K. (1987) Differential patterns of injury to the proximal tubule of renal cortical slices following in vitro exposure to mercuric chloride, potassium dichromate, or hypoxic conditions. Toxicol. Appl. Pharmacol. 90, 261–273.
Stefaniak, M. S., Krumdieck, C. L., Spall, R.D., Gandolfi, A. J., and Brendel, K. (1992) Biochemical and Histological characterization of agar-filled precision cut lung slices in dyanmic organ culture as an in vitro tool. In Vitro Toxicol. 5, 7–19.
Parrish, A. R., Shipp, N. G., Spall, R. D., Dorr, R. T., Krumdieck, C. L., Gandolfi, A. J., and Brendel, K. (1992) Organ culture of rat myocardial slices: An alternative in vitro tool in organ-specific toxicology. Toxicol. Methods 2, 101–111.
Lake, B. G., Beamand, J. A., Japenga, A. C., Renwick, A., Davies, S., and Price, R. J. (1993) Induction of cytochrome P 450 dependent enzyme activities in cultured rat liver slices. Food Chem. Toxicol. 31, 377–386.
Beamand, J. A., Price, R. J., Cunninghame, M. E., and Lake, B. G. (1993) Culture of precision-cut liver slices: effect of some peroxisome proliferators. Food Chem. Toxicol. 31, 137–147.
Ghokale, M. S., Bunton, T. E., Zurlo, J., and Yeager, J. D. (1997) Cytochrome P 450 isozyme activities in cultured rat and mouse liver slices. Xenobiotica 27, 341–355.
Lake, B. G., Ball, S. E., Renwick, A., Tredger, J. M., Kao, J., Beamand, J. A., and Price, R. J. (1997) Induction of CYP 3A isoforms in cultured precision cut human liver slices. Xenobtiotica 27, 1165–1173.
VandenBranden, M., Wrighton, S. A., Ekins, S., Gillespie, J. S., Binkley, S. N., Ring, B. J., et al. (1998) Alterations of the catalytic activities of drug-metabolizing enzymes in cultures of human liver slices. Drug Metab. Dispos. 26, 1063–1068.
Dogetrom, P. and Rothuzien, J. (1993) A species comparison of tolbutamide metabolism in precision-cut liver slices from rats and dogs. Drug Metab. Dispos. 21, 705–709.
Kane, A. S. and Thohan, S. (1996) Dynamic culture offish hepatic tissue slices to assess phase I and phase II biotransformation, in Techniques in Aquatic Toxicology (Ostrander, G.K., ed.), CRC Press, Boca Raton, FL, pp. 371–391.
Ekins, S. (1996) Short term maintenance of phase I and phase II metabolism in precision-cut liver slices in dynamic organ culture. Drug Metab. Dispos. 24, 364–366.
Chenery, R. J. (1988) The utility of hepatocytes in drug metabolism studies, in Progress in Drug Metabolism and Disposition, vol. 11 (Gibson, G. G., ed.), Taylor and Francis, London, pp. 217–265.
Paine, A. J. (1990) The maintenance of cytochrome P-450 in rat hepatocyte cultures to the study of drug metabolism, toxicity and induction of the P-450 system. Chem. Biol. Interact. 74, 1–31.
Smith, P. F., Gandolfi, A. J., Krumdieck, C. L., Putnam, C. W., Zukoski, C. F., Davis, W. M., and Brendel, K. (1985) Dynamic organic culture of precision cut liver slices for in vitro toxicology. Life Sci. 36, 1367–375.
Thohan, S. and Chung, H. (1999) Cytotoxicity profiles for a series of investigational compounds using Liver Slice Technology and human derived cell cultures, in Toxicity Assessment Alternatives: Methods Issues and Alternatives (Salem, H. and Katz, S. A., eds.), Humana Press, Totowa, NJ, pp. 35–52.
Barr, J., Brendel, K., Sipes, I. G., and Weir, A. J. (1991) Liver slices in dynamic organ culture. I. An alternative in vitro technique for the study of rat hepatic drug metabolism. Xenobiotica 21, 331–339.
Fisher, R. L., Shaughnessy, R. P., Jenkins, P. M., Austin, M. L., Roth, G. L., Gandolfi, A. J., and Brendel K. (1995) Dynamic organ culture is superior to multiwell plate culture for maintaining precision-cut tissue slices: optimization of tissue culture. Toxicol. Methods 5, 99–113.
Ekins, S., Murray, G. I., Burke, M. D., Williams, A., Marchant, N. C., and Hawksworth, G. M. (1995) Quantitative differences in phase I and II metabolism between rat precision-cut liver slices and isolated hepatocytes. Drug Metab. Dispos. 23, 1274–1279.
Smith, P. F., Fisher, R., Shubat, P. J., Gandolfi, A. J., Krumdieck, C. L., and Brendel, K. (1987) In vitro cytotoxicity of allyl alcohol and bromobenzenes in a novel organ culture system. Toxicol. Appl. Pharmacol. 87, 509–522.
Thomas, L, DeFeo, B., Mariani, M. F., and Van Rossum, G. D. V. (1989) Comparison of metabolic effects of carbon tetrachloride and 1,2-dicholoroethane added in vitro to slices of rat liver. In Vitro Toxicol. 3, 59–68.
Connors, S., Rankin, D. R., Gandolfi, A. J., and Brendel, K. (1990) Cocaine hepatotoxicity in cultured liver slices: A species comparison. Toxicology 61, 171–190.
Sawyer, J. S., Daller, J. A., Brendel, K., Yohem, K., and Putnam, C. (1994) The hepatotoxicities of endotoxin and ethanol: comparisons in vitro using the precision-cut liver slice model. Life Sci. 55, 1407–1417.
Brodfuehrer, J. I., Chapman, D. E., Wilke, T. J., and Powis, G. (1990) Comparative studies of the in vitro metabolism and covalent binding of 14C-benzene by liver slices and microsomal fraction of mouse, rat, and human. Drug Metab. Dispos. 18, 20–27.
Worboys, P. D., Bradbury, A., and Houston, J. B. (1997) Kinetics of drug metabolism in rat liver slices: Relationship between metabolic clearance and slice uptake rate. Drug Metab. Dispos. 25, 460–467.
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Thohan, S., Rosen, G.M. (2002). Liver Slice Technology as an In Vitro Model for Metabolic and Toxicity Studies. In: Armstrong, D. (eds) Oxidants and Antioxidants. Methods in Molecular Biology™, vol 196. Humana Press. https://doi.org/10.1385/1-59259-274-0:291
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DOI: https://doi.org/10.1385/1-59259-274-0:291
Publisher Name: Humana Press
Print ISBN: 978-0-89603-851-6
Online ISBN: 978-1-59259-274-6
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