Studies on drug metabolism and liver ultrastructure after conjoint treatment with pregnenolone-16alpha-carbonitrile and dl-ethionine.

Zoxazolamine paralysis, hexobarbital anesthesia and digitoxin convulsions were diminished in rats by 3 days of pretreatment with pregnenolone-16alpha-carbonitrile (PCN). Simultaneous injection of dl-ethionine did not block this effect of PCN. Dl-Ethionine decreased, while PCN or PCN + ethionene increased, zoxazolamine metabolism by the 9,000g supernatant fraction of the liver. Dl-ethionine neutralized the influence of PCN and phenobarbital on zoxazolamine metabolism in rats that were pretreated with PCN or phenobarbital for 1 day, and it inhibited the action of phenobarbital on hexobarbital anesthesia. PCN augmented the liver weight of animals given dl-ehtionine whereas dl-ethionine in itself did not. PCN produced SER proliferation in hepatocytes and dl-ethionine caused lipid accumulation, SER proliferation and myelin-figure formation. When administered conjointly, these compounds had an additive effect on the liver cell ultrastructure.