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Effects of carbon tetrachloride on adrenocortical structure and function in guinea pigs.

Publication ,  Journal Article
Brogan, WC; Eacho, PI; Hinton, DE; Colby, HD
Published in: Toxicology and applied pharmacology
August 1984

Studies were carried out to evaluate the effects of carbon tetrachloride (CCl4) on adrenocortical structure and function in guinea pigs. Treatment with CCl4 reduced adrenal microsomal cytochrome P-450 concentrations and markedly decreased adrenal benzo(a)pyrene (BP) hydroxylase and benzphetamine (BZ) demethylase activities. Adrenal microsomal 17 alpha- and 21-hydroxylase activities were relatively unaffected by CCl4. Similar changes in adrenal metabolism resulted from incubation of microsomal suspension with CCl4 plus NADPH in vitro. Morphologically, CCl4 treatment resulted in necrotic changes in the inner portions of the adrenal cortex. The zona reticularis and inner fasciculata contained numerous cells with pyknotic nuclei, fragmented nuclei, and vacuolated cytoplasm. Cells in the outer fasciculata and zona glomerulosa of the adrenals appeared normal. In adrenals obtained from normal guinea pigs, xenobiotic metabolism was highly localized to the inner portion of the cortex, the site of CCl4-induced necrosis. The CCl4-induced type I spectral change, a tentative measure of binding to cytochrome(s) P-450, was also greater in microsomes from the inner than from the outer zones. In addition, the initiation of lipid peroxidation by CCl4 plus NADPH, as well as the formation of covalently bound metabolites from 14CCl4, was far greater with inner than outer zone microsomes. The results indicate that the effects of CCl4 on the adrenal cortex are localized to the inner zone which probably represents the site of activation of the toxin. In addition, adrenal xenobiotic-metabolizing monooxygenases seem to be more vulnerable to the toxic effects of CCl4 than the microsomal steroid hydroxylases.

Duke Scholars

Published In

Toxicology and applied pharmacology

DOI

EISSN

1096-0333

ISSN

0041-008X

Publication Date

August 1984

Volume

75

Issue

1

Start / End Page

118 / 127

Related Subject Headings

  • Toxicology
  • Oxygenases
  • Oxidoreductases, N-Demethylating
  • NADH Dehydrogenase
  • Mixed Function Oxygenases
  • Microsomes, Liver
  • Male
  • Guinea Pigs
  • Cytochrome P-450 Enzyme System
  • Carbon Tetrachloride
 

Citation

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Brogan, W. C., Eacho, P. I., Hinton, D. E., & Colby, H. D. (1984). Effects of carbon tetrachloride on adrenocortical structure and function in guinea pigs. Toxicology and Applied Pharmacology, 75(1), 118–127. https://doi.org/10.1016/0041-008x(84)90082-6
Brogan, W. C., P. I. Eacho, D. E. Hinton, and H. D. Colby. “Effects of carbon tetrachloride on adrenocortical structure and function in guinea pigs.Toxicology and Applied Pharmacology 75, no. 1 (August 1984): 118–27. https://doi.org/10.1016/0041-008x(84)90082-6.
Brogan WC, Eacho PI, Hinton DE, Colby HD. Effects of carbon tetrachloride on adrenocortical structure and function in guinea pigs. Toxicology and applied pharmacology. 1984 Aug;75(1):118–27.
Brogan, W. C., et al. “Effects of carbon tetrachloride on adrenocortical structure and function in guinea pigs.Toxicology and Applied Pharmacology, vol. 75, no. 1, Aug. 1984, pp. 118–27. Epmc, doi:10.1016/0041-008x(84)90082-6.
Brogan WC, Eacho PI, Hinton DE, Colby HD. Effects of carbon tetrachloride on adrenocortical structure and function in guinea pigs. Toxicology and applied pharmacology. 1984 Aug;75(1):118–127.
Journal cover image

Published In

Toxicology and applied pharmacology

DOI

EISSN

1096-0333

ISSN

0041-008X

Publication Date

August 1984

Volume

75

Issue

1

Start / End Page

118 / 127

Related Subject Headings

  • Toxicology
  • Oxygenases
  • Oxidoreductases, N-Demethylating
  • NADH Dehydrogenase
  • Mixed Function Oxygenases
  • Microsomes, Liver
  • Male
  • Guinea Pigs
  • Cytochrome P-450 Enzyme System
  • Carbon Tetrachloride