Effects of pregnenolone-16α-carbonitrile on vitamin E status and protein levels of antioxidant enzymes in male rats fed a vitamin E-supplemented diet

Abstract

The aim of this study was to evaluate the effects of the administration of pregnenolone-16alpha-carbonitrile (PCN), an inducer of the cytochrome P450 3A gene in rats, on vitamin E status and antioxidant enzyme protein levels in rats fed a vitamin E-supplemented diet. Two groups of male Wistar rats were fed for 3 weeks with a basal diet containing 50 ppm of alpha-tocopherol or the same diet containing 10 times more alpha-tocopherol. In the final 3 days, each group was divided into two subgroups which were given a single daily intraperitoneal injection of PCN at 75 mg/kg (groups PCN and PCN+VE) or DMSO (groups DS and DS+VE). PCN treatment alone significantly reduced the alpha-tocopherol content of the liver and plasma and this effect was prevented by supplementation with 10-fold more alpha-tocopherol. alpha-Tocopherol levels in the kidneys, lung, heart, and testes were significantly higher in both vitamin E-supplemented groups than in the control groups. TBARS levels in the liver and lung were significantly increased in both PCN-treated groups, as shown by two-way ANOVA analysis. PCN also caused a significant reduction in protein levels of catalase and glutathione peroxidase (GPx) in both groups. Dietary vitamin E supplementation caused a decrease in liver protein levels of GPx and superoxide dismutase, but not catalase, in both groups and protected against PCN-induced lipid peroxidation, which was caused by CYP3A induction and a reduction in antioxidant enzyme levels.

The antioxidant response of the liver of male Swiss mice raised on a AIN 93 or commercial diet

“…Vitamin E is an important fat-soluble antioxidant in the body and operates with some of the antioxidant enzymes tested in this study, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), to protect cells from attack by ROS [23]. SOD provides the first line of defense against oxygen derived free radicals [6].…”

Vitamin E in Oxidant Stress-Related Cardiovascular Pathologies: Focus on Experimental Studies

“…However, a deeper understanding of its source and of its role in cardiovascular pathology is necessary before new trials are attempted. More competent anti-oxidative reagents are awaited, superoxide dismutase mimetics, thiols, xanthine oxidase and NAD(P)H oxidase inhibitors, which regulate intracellular redox reaction and subsequently inhibit oxidative stress, are among promising candidates of future drug developments currently receiving much interest [197,200,211].…”