INCREASE IN RAT LIVER TRYPTOPHAN OXYGENASE ACTIVITY AFTER ACUTE ETHANOL TREATMENT: DEPENDENCE ON FEEDING STATE AND ROUTE OF ETHANOL ADMINISTRATION

Abstract

A time course and dose-response study of the effects of acute ethanol administration on the activlty of liver tryptophan oxygenase was carried out in fed and starved rats. Ethanol doses ranging from 0.5 to 5.0 g/kg body weight were given either intragastrically or intraperitoneally. In a detailed time curve for an oral 3.3 g/kg dose of ethanol in starved rats, the total activity of tryptophan oxygenase was increased 1.5-fold 2 hr after ethanol administration and the activity of the holoenzyme (haem-saturated form) increased one hour later, thus indicating that increased haem-saturation is not the critical stimulus for accumulation of the enzyme after acute ethanol ingestion. Both the total and holoenzyme activities reached a peak, whlch was4.5–5.5 times the control activity, 5–6 hr after ethanol treatment. The increase in the enzyme activities was not directly dependent on the dose of ethanol, but rather the peak blood ethanol concentration, which had to reach a critical level to trigger enzyme activation. In fed rats when ethanol was given orally, this critical blood ethanol level was not achieved even with the highest ethanol dose and no significant increases in tryptophan oxygenax activities were seen. 4-Methylpyrazole (75 mg/kg) inhibited the ethanol-induced increase in the total tryptophan oxygenase actlvity by 30%, but did not affect that in the holoenzyme activity. Cyanamide (5 mg/kg) did not affect the ethanol-induced increases in either total enzyme or holoenzyme activities. t -Butanol (1.0 g/kg) caused increases of the same order of magnitude as ethanol did. It was concluded that 70% of the increase in total tryptophan oxygenase activity after acute ethanol ingestion is probably caused by an action of ethanol itself. while 30% may be caused by ethanol metabolism. However, the increase in haem-saturation was apparently caused by an action of ethanol itself.