Comparison of cytochrome P-450 content and activities in liver microsomes of seven animal species, including man

Abstract

The cytochrome P-450 content found in human livers obtained post mortem was between 0.21-0.42 nmol/mg protein. The kinetic parameters of the mono-oxygenase activities--Km and Vmax--were determined in liver microsomes for N-demethylation (aminopyrine, benzphetamine, ethylmorphine), O-demethylation (4-nitroanisole), O-deethylation (7-ethoxycoumarin) and hydroxylation (benzo[a]pyrene), in an attempt to establish an inter-species comparison between man and the six animal species studied. The four substrates studied (aminopyrine, benzphetamine, ethylmorphine, benzo[a]pyrene) were shown to be less active in humans than the male rat, which is the most commonly used model. However, other animal species, such as the female Sprague-Dawley rat and the pig, are much more similar to man. From a procedural point of view, the optimal substrate concentrations vary from one experimental species to another. Due to the apparent Km observed, for example, the activities of the guinea-pig require a higher substrate concentration.

Effect of quinidine on the dextromethorphan O‐demethylase activity of microsomal fractions from human liver.

“…The values for total cytochrome P-450 content of the liver samples studied were similar to those reported in the literature when livers were obtained either post mortem (Souhaili-el Amri et al, 1986) or from kidney transplant donors shortly after circulatory arrest (Von Bahr et al, 1980;Meier et al, 1983) (Ramachander et al, 1977;Park et al, 1984;Barnhart & Massad, 1979;Schmid et al, 1985;Pfaff et al, 1983;Mascher, 1987;Motassin et al, 1987), but only Kronbach et al (1987) used h.p.l.c. to assay the in vitro production of dextrorphan by human liver microsomes.…”

Metabolism of diazepam and related benzodiazepines by human liver microsomes

“…Table II shows the protein concentrations, cytochrome P450 specific contents, NADPH cytochrome c (P450) reductase specific activities and ethylmorphine demethylase activities of the human liver microsomal preparations used here. All of the values are within published ranges for microsomes from similar sources (20)(21)(22)(23), which confmns that the preparation and use of these reconstituted enzyme systems was appropriate in the present studies.…”

Comparison in the efficiency of different murine lines for genotoxicity assays

“…The opposing differences as for the expression of the genotoxic damage caused by the CF could be since in response to different levels of expression of the genes that code for the cytochrome P-4501A1 enzyme in the liver, the mice and rats differ genetic and epigenetically when keeping in mind this fundamental hepatic enzyme in the I phase of the xenobiotic metabolism that participates in the metabolism of the CF in the liver when being used as cytostatic drug (Amri et al , 1986; Bell et al , 1993; Jana et al , 1998). …”