Pregnenolone-16-carbonitrile (PCN) is a synthetic steroid and an
inducer of the cytochrome P450 3A gene in rats. The aim of this study was to evaluate
the effects of PCN administration on vitamin-E status and antioxidant enzyme protein
levels in rats fed a vitamin-E supplemented diet. Two groups of Wistar rats were fed
for three weeks with a basal diet (containing 50 ppm of -tocopherol) or the same diet containing tenfold more -tocopherol. In the last three days, each group was divided
into two subgroups which were given a single intraperitoneal injection of PCN at 75
mg/kg/day (P50 and P500 groups) or DMSO (C50 and C500 groups). PCN
significantly reduced -tocopherol contents in the liver and plasma. Tenfold
supplementation of -tocopherol (P500 group) could return liver -tocopherol levels to that of the C50 group. The TBARS concentration was significantly elevated by
PCN administration in the liver and lung by Two-way ANOVA analysis. PCN showed
a significant reduction in the protein levels of catalase and glutathione peroxidase (GPx). Dietary vitamin-E supplementation altered the protein levels of GPx and
superoxide dismutase, but not catalase. Vitamin-E supplementation protected against
PCN-induced lipid peroxidation and compromized vitamin-E status by CYP3A
induction and antioxidant enzyme reduction. The mechanism of this protection
appears to be due to scavenging the reactive metabolite by vitamin-E rather than increasing antioxidant enzyme levels.
