Effect of alcohol on the heme and porphyrin synthesis interaction with phenobarbital and pyrazole

The effect of alcohol in addition with respectively phenobarbital and pyrazole on the heme porphyrin synthesis in the liver of male rats was studied. After a single dose of 2 g alcohol/kg p.o. the activity of the delta-aminolevulinic acid synthetase (ALA synthetase) in the liver of starving rats increased 2- to 3-fold within 3 h. The porphyrin concentration in the liver of these animals was increased maximally by 75%. The activity of the delta-aminolevulinic acid dehydratase (ALA dehydratase), of the microsomal monoxygenase and of the concentration of cytochrome P-450 and ATP in the liver were not altered. A previous injection of pyrazole (6 mumol/kg) could abolish the inducing effect of alcohol on the ALA synthetase. The inducing effect of alcohol was increased by a previous injection of phenobarbital (80 mg/kg). The activity of the microsomal monoxygenase and the concentration of cytochrome P-450 was not altered by administration of an 8% alcohol solution instead of drinking water. The activity of the ALA synthetase in the liver of these animals was increased 3- to 4-fold only when they starved before sacrifice. In fed animals the activity of this enzyme was in the range of the control animals. The increase of the cytochrome P-450 concentration in the liver after 80 mg phenobarbital sodium/kg was lowered by alcohol. The experiments show that alcohol differs from other known porphyrinogenic agents. An alteration of the cytochrome P-450 concentration could not be demonstrated as the cause of the induction of the ALA synthetase. The observed porphyrinogenic effect is not caused by alcohol itself by either by its metabolites or by the changes of the liver metabolism caused by the effect of alcohol on the NAD/NADH ratio.