Biotransformation of scoparone used to monitor changes in cytochrome P450 activities in primary hepatocyte cultures derived from rats, hamsters and monkeys

Differences in the effects of model inducers of cytochrome P450 on the biotransformation of scoparone in rat and hamster liver

“…It is not very likely that this has occurred in our experiments, since the bulk of the ether used will be evaporated during microsome preparation. Moreover, in an earlier publication (Mennes et al 1991) we have shown that species differences were observed in hepatocytes derived from untreated rats and hamsters after pentobarbital anaesthesia, which differences are highly comparable with the data obtained in the present study.…”

“…In primary cultures of rat hepatocytes the individual P450s decline at a rate similar to that of the total P450 concentration thus reducing biotransformation rates while maintaining metabolic profiles Mennes et al 1991). In contrast to rat hepatocytes, in hamster and monkey liver cells the metabolic profile of the coumarin derivative scoparone (6,7-dimethoxycoumarin), which in rats depends on at least four P450s (Miiller-Enoch et al 1985), is changed during primary culture (Mennes et al 1991). This indicates a certain degree of variability in the rates of decline of the P450 enzymes involved in hepatocytes from the latter two species.…”

“…Inter-species differences in biotransformation can be studied in vivo, in microsomal incubates and in primary hepatocyte cultures (Holme et al 1986;Powis et al 1987;Seddon et al 1989;Mennes et al 1991). In such cell systems, the level of cytochrome P450 shows a decrease during culture time, usually resulting in a drastically lowered P450 activity (Paine 1990;Wortelboer et al 1990;Mennes et al 1991).…”

“…In such cell systems, the level of cytochrome P450 shows a decrease during culture time, usually resulting in a drastically lowered P450 activity (Paine 1990;Wortelboer et al 1990;Mennes et al 1991). In primary cultures of rat hepatocytes the individual P450s decline at a rate similar to that of the total P450 concentration thus reducing biotransformation rates while maintaining metabolic profiles Mennes et al 1991).…”

“…In such cell systems, the level of cytochrome P450 shows a decrease during culture time, usually resulting in a drastically lowered P450 activity (Paine 1990;Wortelboer et al 1990;Mennes et al 1991). In primary cultures of rat hepatocytes the individual P450s decline at a rate similar to that of the total P450 concentration thus reducing biotransformation rates while maintaining metabolic profiles Mennes et al 1991). In contrast to rat hepatocytes, in hamster and monkey liver cells the metabolic profile of the coumarin derivative scoparone (6,7-dimethoxycoumarin), which in rats depends on at least four P450s (Miiller-Enoch et al 1985), is changed during primary culture (Mennes et al 1991).…”