Skip to main content
Log in

Blood clearance tests for detecting 2,3,7,8-tetrachlorodibenzo-p-dioxin hepatotoxicity in rats and rabbits

  • Published:
Archives of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

The objective was to determine if a blood clearance test would detect liver dysfunction in rats and rabbits treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Guinea pigs were included as a negative control, because TCDD does not produce detectable hepatotoxicity in this species. TCDD was given as a single dose to male rats (25μg/kg, po), rabbits (25μg/kg, ip) and guinea pigs (2μg/kg, ip) and liver function was assessed 10 days later by determining blood clearance of indocyanine green (ICG) and ouabain. Activity in serum of sorbitol dehydrogenase (SDH), glutamic pyruvic transaminase (SGPT) and gamma glutamyl transpeptidase (γGTP) were also measured and light microscopy performed on the liver. The results showed that hepatotoxicity in the rabbit could be detected by a reduction in ICG blood clearance and an elevation in SDH activity. In the rat, ouabain blood clearance was reduced and SDH activity elevated. None of the liver function tests were altered in the guinea pig. These results underline the usefulness of blood clearance tests using ICG and ouabain in detecting TCDD hepatotoxicity in animals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bleiberg, J., M. Wallen, R. Brodkin, and I. L. Applebaum: Industrially acquired porphyria. Arch. Dermatol.89, 793 (1964).

    PubMed  Google Scholar 

  • Courtney, K. D., D. W. Gaylor, M. D. Hogan, H. L. Falk, R. R. Bates, and I. Mitchell: Teratogenic evaluation of 2,4,5,-T. Science168, 864 (1970).

    PubMed  Google Scholar 

  • Cox, E., G. Roxburgh, and S. E. Wright: The metabolism of ouabain in the rat. J. Pharm. Pharmacol.11, 535 (1959).

    PubMed  Google Scholar 

  • Crummett, W. B., and R. H. Stehl: Determination of chlorinated dibenzo-p-dioxins and dibenzofurans in various materials. Environ. Health Perspect.5, 15 (1973).

    PubMed  Google Scholar 

  • Greig, J. B., G. Jones, W. H. Butler, and J. M. Barnes: Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Food Cosmet. Toxicol.11, 585 (1973).

    PubMed  Google Scholar 

  • Gupta, B. N., J. G. Vos, J. A. Moore, J. G. Zinkl, and B. C. Bullock: Pathological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in laboratory animals. Environ. Health Perspect. Experimental Issue No. 5, 125 (1973).

  • Hwang, S. W.: Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the biliary excretion of indocyanine green in rat. Environ. Health Perspect. Experimental Issue No. 5, 227 (1973).

  • Klaassen, C. D., and G. L. Plaa: Plasma disappearance and biliary excretion of indocyanine green in rats, rabbits and dogs. Toxicol. Appl. Pharmacol.15, 374 (1969).

    PubMed  Google Scholar 

  • May, G.: Chloracne from the accidental production of tetrachlorodibenzodioxin. Brit. J. Indust. Med.30, 276 (1973).

    Google Scholar 

  • McConnell, E. E., J. A. Moore, J. K. Haseman, and M. W. Harris: The comparative toxicity of chlorinated dibenzo-p-dioxins in mice and guinea pigs. Toxicol. Appl. Pharmacol.44, 335 (1978).

    PubMed  Google Scholar 

  • McDevitt, D. G., A. S. Nies, and G. R. Wilkinson: Influence of phenobarbital on factors responsible for hepatic clearance of indocyanine green in the rat: relative contributions of induction and altered liver blood flow. Biochem. Pharmacol.26, 1247 (1977).

    PubMed  Google Scholar 

  • Paumgartner, G., P. Probst, R. Kraines, and C. M. Leevy: Kinetics of indocyanine green removal from blood. Ann N.Y. Acad. Sci.170, 134 (1970).

    Google Scholar 

  • Peterson, R. E., B. V. Madhukar, K. H. Yang, and F. Matsumura: Depression of adenosine triphosphatase activities in isolated liver surface membranes of 2,3,7,8-tetrachloro dibenzo-p-dioxin-treated rats: Correlation with effects on ouabain biliary excretion and bile flow. J. Pharmacol. Exp. Ther.210, 275 (1979).

    PubMed  Google Scholar 

  • Peterson, R. E., N. Hamada, K. H. Yang, B. V. Madhukar and F. Matsumura: Reversal of 2,3,7,8-tetrachlorodibenzo-p-dioxin induced depression in ouabain biliary excretion by pregnenolone-16α-carbonitrile and spironolactone in isolated rat perfused livers. Toxicol. Appl. Pharmacol. In press (1979).

  • Poland, A., and A. Kende: 2,3,7,8-Tetrachlorodibenzo-p-dioxin: Environmental contaminant and molecular probe. Fed. Proc.35, 2404 (1976).

    PubMed  Google Scholar 

  • Reggiani, G.: Medical problems raised by the TCDD contamination in Seveso, Italy. Arch. Toxicol.40, 161 (1978).

    Google Scholar 

  • Russell, J. Q., and C. D. Klaassen: Species variations in the biliary excretion of ouabain. J. Pharmacol. Exp. Ther.183, 513 (1972).

    PubMed  Google Scholar 

  • Schulz, K. H.: Klinische und experimentelle Untersuchungen zur atiologie der chloracne. Arch. Klin. Exp. Dermatol.206, 589 (1957).

    PubMed  Google Scholar 

  • Schwetz, B. A., J. M. Norris, G. L. Sparschu, V. K. Rowe., P. J. Gehring, J. L. Emerson, and C. G. Gerbig: Toxicology of chlorinated dibenzo-p-dioxins. Environ. Health Perspect. Experimental Issue No. 5, 87 (1973).

  • Secchi, G. C., and A. Ghidoni: Interesse clinico della determinazione dell' attivita sorbitolderdrogenasica plasmatica in patalogia epatica. Enzymol. Biol. Clin.2, 99 (1962).

    Google Scholar 

  • Steel, R. G. D., and J. H. Torrie: Principles and Procedures of Statistics. New York: McGraw-Hill (1960).

    Google Scholar 

  • Wiesner, I. S., H. M. Rawnsley, F. P. Brooks, and J. R. Senior: Sorbitol dehydrogenase in the diagnosis of liver disease. Am. J. Dig. Dis.10, 147 (1965).

    PubMed  Google Scholar 

  • Wilkinson, G. R., and S. Schenker: Drug disposition and liver disease. Drug Metab. Rev.4(2), 139 (1975).

    PubMed  Google Scholar 

  • Wilkinson, G. R., and S. Schenker: Effects of liver disease on drug disposition in man. Biochem. Pharmacol.25, 2675 (1976).

    PubMed  Google Scholar 

  • Yang, K. H., W. A. Croft, and R. E. Peterson: Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on plasma disappearance and biliary excretion of foreign compounds in rats. Toxicol. Appl. Pharmacol.40, 485 (1977).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by USPHS ES01332. Preliminary results were presented at the Eighteenth Annual Meeting of the Society of Toxicology, New Orleans, LA, March 1979.

Supported by USPHS predoctoral training grant ES07071-01.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Seefeld, M.D., Albrecht, R.M., Gilchrist, K.W. et al. Blood clearance tests for detecting 2,3,7,8-tetrachlorodibenzo-p-dioxin hepatotoxicity in rats and rabbits. Arch. Environ. Contam. Toxicol. 9, 317–327 (1980). https://doi.org/10.1007/BF01057411

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01057411

Keywords

Navigation