Summary
In rats, the activity of some hepatic redox-enzymes was measured following the administration of the enzyme-inducing substances phenobarbital, α-hexachlorocyclohexane (α-HCH = α-benzene hexachloride), CFT 1201 (phenyl-diallylacetic acid ester of diethylaminoethanol), or 3,4-benzpyrene. In particular, the time course of changes in enzyme activities was studied.
1. α-HCH and CFT 1201, like phenobarbital, increase the concentration of cytochrome P450 and accelerate the NADPH-dependent reduction of cytochrome c. All three substances reduce the activity of NADH-cytochrome c-reductase. On the other hand, only α-HCH, increases aldehyde oxidase activity in the hyaloplasm.
2. Phenobarbital and α-HCH both enhance the rate of demethylation of aminopyrine considerably more than they increase the concentration of cytochrome P450. Similarly, benzpyrene produces an increase in the rate of hydroxylation of acetanilide that is higher than the increase in concentration of P450.
3. CFT 1201 inhibits acetanilide-oxidation in vivo, but not in vitro.
4. Phenobarbital induces microsomal enzymes more strongly than does α-HCH, whereas this latter compound—as earlier observations have shown—stimulates liver cell proliferation much more than phenobarbital.
Zusammenfassung
Die Aktivität einiger Redoxenzyme der Rattenleber wurde nach Behandlung mit folgenden induzierenden Substanzen untersucht: Phenobarbital, α-Hexachlorcyclohexan (α-HCH), CFT 1201 (Phenyldiallylessigsäure-diäthylaminoäthylester) sowie 3,4-Benzpyren. Der zeitliche Ablauf der Aktivitätsänderungen wurde verfolgt.
1. α-HCH und CFT 1201 erhöhen ebenso wie Phenobarbital die Cytochrom-P450-Konzentration und die NADPH-abhängige Reduktion von Cytochrom c. Die Aktivität der NADH-Cytochrom c-Reduktase wird durch die drei Substanzen gesenkt. Die Aktivität der Aldehyd-Oxydase aus Hyaloplasma wird nur durch α-HCH beschleunigt.
2. Phenobarbital und α-HCH steigern die Demethylierungsrate von Aminopyrin wesentlich mehr als die Konzentration des Cytochroms P450. Benzpyren erhöht die Hydroxylierungsgeschwindigkeit von Acetanilid stärker als die Konzentration des P450.
3. CFT 1201 hemmt die Acetanilid-Oxydation nur in vivo, nicht aber in vitro.
4. Phenobarbital induziert die mikrosomalen Enzyme stärker als α-HCH, während dieses — wie frühere Befunde zeigten — zu einer stärkeren Proliferation der Leberzellen führt.
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Herrn Prof. Dr. Ludwig Lendle zum 70. Geburtstag gewidmet.
Teile unserer Ergebnisse haben wir bereits in Form von Vorträgen veröffentlicht: Schulte Hermann et al., 1966; Koransky et al., 1966.
Wir danken für Unterstützung durch die Deutsche Forschungsgemeinschaft.
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Koransky, W., Magour, S., Noack, G. et al. Über den Einfluß induzierender Substanzen auf Fremdstoff-Oxydasen und andere Redoxenzyme der Leber. Naunyn-Schmiedebergs Arch. Pharmak. u. Exp. Path. 263, 281–296 (1969). https://doi.org/10.1007/BF00537603
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DOI: https://doi.org/10.1007/BF00537603