Use of XXXX organ slices to evaluate the biotransformation and drug-induced side-effects of pharmaceuticals.

@entity1 @entity137 @entity101 @entity870 @entity5322 @entity409 @entity2041 @entity205 @entity35
@entity1 liver and kidney organ slices were used to investigate the biotransformation competence of the slices in combination with several markers of cell viability and function. The immunosuppressant @entity205 ( @entity870 ) is extensively metabolized in liver slices to the three known primary metabolites and many secondary metabolites. In kidney cortex slices the biotransformation of @entity870 is far more pronounced in @entity1 than in @entity35 . In @entity1 liver slices, levels of @entity5322 , the proteins metabolizing @entity870 , are depressed about 25% by 1 and 10 mumol/L @entity870 within 24 h, indicating that high blood or tissue concentrations will inhibit @entity870 clearance. A clinical marker for @entity409 is the release of cellular alpha- @entity2041 -S-transferases (alpha GST). In this study the alpha GST levels were used to assess donor organ quality, organ slice incubation conditions, and compound exposure. A marker for cell death in @entity1 cells is the solubilization and release of nuclear matrix proteins (Numa). Increases were apparent only after 48 h of culture. A side-effect of @entity870 is that it induces @entity101 and perturbs the lipid profile of transplant recipients. A potential marker for lipid disturbances is levels of serum lipoprotein (a) (Lp(a)), which is synthesized in the liver and found only in @entity1 , apes, and nonhuman primates. @entity870 increases Lp(a) levels in the @entity1 liver slice cultures about 2-fold. This study has demonstrated that the biotransformation capability of the organ slices contributes to the optimization of the in vitro system and to the evaluation of markers for drug induced side-effects or @entity137 .(ABSTRACT TRUNCATED AT 250 WORDS)
