Previous studies have shown that antibodies in the sera of halothane hepatitis patients recognize trifluoroacetylated liver microsomal proteins (neoantigens) of 100 kDa, 76 kDa, 59 kDa, 57 kDa, and 54 kDa. In the present investigation, factors that might affect the level of expression of the neoantigens were investigated. A study of the time course of neoantigen expression in halothane-treated rats revealed that the 100 kDa, 76 kDa, 59 kDa, and 57 kDa neoantigens were longer-lived than the 54 kDa neoantigen and could be detected in the liver up to a week after the administration of halothane. Pretreatment of rats with isoniazid, which is known to induce cytochrome P-450 IIE1, appeared to increase the expression of each of the neoantigens, whereas inducers of several other forms of cytochrome P-450 had either very little effect or decreased the expression of several of the neoantigens. Female rats appeared to express some of the neoantigens at a higher level than that found in males. Examination of the organ distribution of the trifluoroacetylated neoantigens showed that, of the tissues examined, only the liver contained appreciable levels of the neoantigens. These results indicate that the level of expression and possibly the immunogenicity of the trifluoroacetylated neoantigens may be influenced by their half-lives and the repertoire of cytochrome P-450 present in the liver.
|Original language||English (US)|
|Number of pages||6|
|Journal||Drug Metabolism and Disposition|
|State||Published - Nov 1 1990|
ASJC Scopus subject areas
- Pharmaceutical Science