Archives of Toxicology

, Volume 61, Issue 2, pp 155–157 | Cite as

Cytochrome P-450-dependent covalent binding of carbon disulfide to rat liver microsomal protein in vitro and its prevention by reduced glutathione

  • R. R. Dalvi
Short Communication
  • 39 Downloads

Abstract

Carbon disulfide, a hepatotoxic solvent, is metabolized by liver microsomal enzymes to reactive sulfur atoms which get bound to the microsomal enzymes, causing inhibition of the enzyme system. These studies were carried out to examine whether glutathione can protect the liver enzymes from the sulfur binding and against carbon disulfide toxicity. When liver microsomes isolated from phenobarbital-pretreated rats were incubated with35S-CS2, NADPH and glutathione, almost 60% decrease in sulfur binding to microsomal protein was observed under the experimental conditions. It was further observed that the addition of glutathione to microsomal incubations resulted in almost complete recovery of the activity of the enzyme system as measured by cytochrome P-450 concentration and benzphetamine metabolism. The data suggest that the presence of glutathione in sufficient amount in the liver of subject exposed to CS2 may significantly decrease the liver toxicity of this highly toxic compound.

Key words

Carbon disulfide Rats Liver microsomal enzymes Glutathione 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Beutler E (1976) Disorders in glutathione metabolism. Life Sci 16: 1499–1506Google Scholar
  2. Catignani GL, Neal RA (1975) Evidence for the formation of a protein bound hydrodisulfide resulting from the microsomal mixed function oxidase catalyzed desulfuration of carbon disulfide. Biochem Biophys Res Commun 65: 629–636Google Scholar
  3. Cochin J, Axelrod J (1959) Biochemical and pharmacological changes in the rat following chronic administration of morphine, nalorphine and normorphine. J Pharmacol Exp Ther 125: 105–110Google Scholar
  4. Dalvi RR, Neal RA (1978) Metabolism in vivo of carbon disulfide to carbonyl sulfide and carbon dioxide in the rat. Biochem Pharmacol 27: 1608–1609Google Scholar
  5. Dalvi RR, Robbins TJ (1978) Comparative studies on the effect of cadmium, cobalt, lead and selenium on hepatic microsomal monooxygenase enzymes and glutathione levels in mice. J Environ Pathol Toxicol 1: 601–607Google Scholar
  6. Dalvi RR, Poore RE, Neal RA (1974) Studies of the metabolism of carbon disulfide by rat liver microsomes. Life Sci 14: 1785–1796Google Scholar
  7. Dalvi RR, Hunter AL, Neal RA (1975) Toxicological implications of the mixed-function oxidase catalyzed metabolism of carbon disulfide. Chem-Biol Interact 10: 347–361Google Scholar
  8. Kuljak S, Stern P (1971) Protective effects of glutathione and xanthinol nicotinate against carbon disulphide poisoning in the mouse. Arh Hig Rada Toksikol 22: 137–141Google Scholar
  9. Mitchell JR, Jollow DJ, Poter WZ, Gillette JR, Brodie BB (1973) Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J Pharmacol Exp Ther 187: 211–217Google Scholar
  10. Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 239: 2370–2378Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • R. R. Dalvi
    • 1
  1. 1.Toxicology Laboratory, School of Veterinary MedicineTuskegee UniversityTuskegeeUSA

Personalised recommendations