No inhibition of γ‐glutamyl transpeptidase‐positive foci by vitamin e with or without phenobarbital

Abstract

The effect of vitamin E on γ‐glutamyl transpepti‐dase‐positive foci, with or without phenobarbital, was investigated. Groups of six female Sprague‐Dawley rats were initiated with diethylnitrosamine (15 mg/kg) at 24 hours of age. After weaning, they were fed diets with 10% (wt/wt) fish oil; the diets contained 0, 5,000, or 15,000 ppm vitamin E supplementation with or without phenobarbital (500 ppm) for six months. Phenobarbital significantly increased liver weight and liver weight as a percentage of body weight ( p < 0.05), suggesting a liver hypertrophic effect of phenobarbital. Phenobarbital significantly decreased hepatic phospholipid arachidonate, eicosapentaenoate, and docosa‐hexaenoate (p < 0.05) this may indicate that phenobarbital stimulates phospholipase A₂ activity and results in the increased release of polyunsaturated fatty acids from phos‐pholipids and the decrease of hepatic phospholipid polyunsaturated‐to‐saturated fat ratio. In rats fed phenobarbital, hepatic vitamin E content was lower than in rats fed no phenobarbital; this suggests that phenobarbital causes oxidative stress or induces enzymes that metabolize the vitamin. Phenobarbital exposure significantly increased hepatic prostaglandin F_2a and glutathione S‐transferase activity (p < 0.05). Vitamin E did not influence hepatic γ‐glutamyl trans‐peptidase‐positive foci area and number with or without phenobarbital, and phenobarbital showed a strong promoting action on enzyme‐altered hepatic foci.