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.
D000818:Animals; D001847:Bone Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004790:Enzyme Induction; D005260:Female; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008862:Microsomes, Liver / Q000201:enzymology*; D010243:Paralysis / Q000139:chemically induced / Q000188:drug therapy; D010634:Phenobarbital / Q000008:administration & dosage / Q000627:therapeutic use*; D010672:Phenytoin / Q000008:administration & dosage / Q000627:therapeutic use*; D011285:Pregnenolone Carbonitrile / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D014801:Vitamin A / Q000009:adverse effects* / Q000378:metabolism; D015049:Zoxazolamine / Q000494:pharmacology
D014801:Vitamin A; D011285:Pregnenolone Carbonitrile; D010672:Phenytoin; D015049:Zoxazolamine; D010634:Phenobarbital