Assessment of drug-drug interaction for silymarin.

Silymarin was assessed for drug-drug interaction by permeability studies with Caco-2 cells, for cytochrome P450 induction with human primary hepatocytes and for cytochrome P450 inhibition with human liver microsomes. Studies with Caco-2 cells revealed no interference of silymarin with the permeability of nifedipine. Silymarin did not induce cytochromes P450 2C9 and 3A4 at concentrations of 0.

Polychlorinated aromatic hydrocarbon lethality, mixed-function oxidase induction, and uroporphyrinogen decarboxylase inhibition in the chick embryo: dissociation of dose-response relationships.

Effects on survival of chick embryos and on the activity of hepatic enzymes involved in heme biosynthesis and hemoprotein function were compared as a function of dose of 3,4,3',4'-tetrachlorobiphenyl (TCB), 3,4,5,3',4',5'-hexachlorobiphenyl (HCB), 2,3,6,2',3',6'-HCB, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at 24 hr and at 9 days after polyhalogenated aromatic hydrocarbon (PAH) administration. 2,3,6,2',3',6'-HCB did not alter enzyme activities or survival. The other PAH increased delta-aminolevulinic acid synthetase up to 10- to 20-fold after 24 hr or 9 days of exposure.

Benoxaprofen suppression of polychlorinated biphenyl toxicity without alteration of mixed function oxidase function.

Polyhalogenated hydrocarbons are widely distributed environmental pollutants. Several members of the class, including certain polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans and dibenzodioxins, produce a characteristic toxicity syndrome, manifestations of which are increased mortality, oedema, hyperkeratosis, thymic involution and hepatotoxicity. The toxic hydrocarbons are also inducers of cytochrome P448-mediated mixed function oxidases.

Kinetic evidence for heterogeneous responsiveness of mixed function oxidase isozymes to inhibition and induction by allylisopropylacetamide in chick embryo liver.

Changes in hepatic mixed function oxidase kinetics after administration of allylisopropylacetamide (AIA) to chick embryos indicate that the activities of different cytochrome P-450 isozymes, including those participating in the metabolism of the same substrates, can be simultaneously increased and inhibited by a single xenobiotic. Up to 4 h after administration in ovo, or in vitro, AIA exclusively inhibited mixed function oxidases. At 24 h after administration in ovo, AIA simultaneously decreased the Vmax of the isozymes active in 7-ethoxycoumarin deethylation and in biphenyl and antipyrine hydroxylations in control liver and caused new isozymes with higher Km and Vmax values to appear.