Microsomal enzyme inducers and hypervitaminosis A in rats.

Pretreatment of rats with pregnenolone-16alpha-carbonitrile (PCN) completely prevented the osseous lesions produced by vitamin A overdosage, whereas pretreatment with phenobarbital or with phenytoin (diphenylhydantoin) provided only partial prophylaxis. These microsomal enzyme inducers also decreased vitamin A concentration in the liver and seemed to protect against hypervitaminosis A by enhancing the metabolism of the vitamin. Electron microscopy of the liver showed large, vitamin A-storing perisinusoidal cells. The number, size, and lipid content of these cells were decreased in rats treated simultaneously with vitamin A and PCN, but not in rats pretreated with phenobarbital or phenytoin. Vitamin A, given alone, produced moderate accumulation of smooth endoplasmic reticulum (SER) in hepatocytes, without accelerating microsomal drug-metabolizing enzyme activity; phenobarbital, phenytoin, and PCN also elicited SER accumulation, particularly when administered with vitamin A.