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5141092 
Journal Article 
Effects of Carbon Tetrachloride Administration to Guinea Pigs on Cytochromes P-450 and Antioxidant Levels in the Inner and Outer Zones of the Adrenal Cortex 
Staats, DA; Lohr, DP; Colby, HD 
1990 
Yes 
Drug Metabolism and Disposition
ISSN: 0090-9556
EISSN: 1521-009X 
18 
4 
The effects of carbon-tetrachloride (56235) (CCl4) on the adrenal cytochrome-P-450 (P450) monooxygenase system were studied in guinea-pigs. The ability of alpha-tocopherol (vitamin-E) to modulate the effects was also examined. Male English-short-hair-guinea-pigs were fed synthetic diets deficient or adequate in vitamin-E for 9 to 10 weeks and then injected intraperitoneally with 0 or 0.4mg/kg CCl4. Animals were killed after 24 hours and weighed. The adrenals were removed and weighed. Adrenal cytosolic ascorbic-acid concentration and microsomal vitamin-E and P450 concentrations and benzo(a)pyrene-hydroxylase (BaPOH) and steroid-21-hydroxylase (S21OH) activity in the inner and outer cortical zones were determined. Body and adrenal weights were not significantly affected by diet. Vitamin-E concentrations in the cortical outer zone were significantly higher than in the inner zone in guinea-pigs fed the vitamin-E adequate diet. Cytosolic ascorbic-acid concentration was not affected by diet. Vitamin-E concentrations in the outer and inner zones were significantly decreased in animals on the vitamin-E deficient diet. CCl4 did not significantly affect vitamin-E concentrations in the inner or outer cortical zone. Cytosolic ascorbic-acid concentration was significantly decreased by CCl4. The decrease was not affected by vitamin-E status. CCl4 significantly decreased inner and outer zone P450 concentration and BaPOH and S21OH activity. These changes were independent of vitamin-E status. The authors conclude that CCl4 causes significant functional changes in portions of the adrenal cortex. Microsomal vitamin-E concentration appears to have little or no effect on CCl4 induced degradation of the P450 monooxygenase system.