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Abstract
The effect of repeated (4 weeks) oral administration of 2,4-, 2,5- or 2,6-xylidine
(at dose levels of 400--500 mg/kg/day) on the morphology and microsomal drug metabolising
enzyme activity of the liver was studied in rats. All 3 isomers caused hepatomegaly
which was considered to be due to proliferation of the smooth endoplasmic reticulum.
Decreases in glycogen content and glucose-6-phosphatase activity were demonstrated
histochemically. Biochemical investigations showed increases in microsomal protein
and cytochrome P-450 content in rats dosed with 2,4- or 2,5-xylidine and in glucuronyltransferase
activity in rats given 2,4-, 2,5- or 2,6-xylidine. Aniline hydroxylase activity was
increased in all treated rats except males dosed with 2,6-xylidine. The results of
the study indicate that all isomes of xylidine can be inducers of microsomal drug-metabolising
enzyme activity, that they may be metabolised by oxidation and that the xylidine molecule
may be eliminated as a conjugate with glucuronic acid.