ToxSci Advance Access published online on May 5, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh156
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Comparative Biosciences and the Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin, 53706
* To whom correspondence should be addressed. E-mail: elfarra{at}svm.vetmed.wisc.edu.
3-Butene-1,2-diol (BDD) is a major metabolite of 1,3-butadiene (BD), but the role of BDD in BD toxicity and carcinogenecity remains unclear. In this study, the acute toxicity of BDD was investigated in male Sprague-Dawley rats and B6C3F1 mice. Of the rats given 250 mg/kg BDD, 2 out of 4 died within 24 h; rats experienced hypoglycemia, significant alterations of liver integrity tests, and had lesions in the liver 4 h after treatment, but no lesions were detected in extrahepatic tissues. Rat hepatic GSH and GSSG levels were significantly depleted at both 1 and 4 h after the BDD treatment. Rats administered 200 mg/kg BDD also had liver lesions but no death or hypoglycemia was observed 4 or 24 h after treatment; these rats had depleted hepatic GSH and GSSG levels at 1 h but not at 4 or 24 h after treatment. Mice administered 250 mg/kg BDD exhibited modest alterations of liver integrity tests, but no death, hypoglycemia, or lesions in any tissue, and hepatic GSH and GSSG levels were depleted at 1 h but not at 4 h. The plasma half-life of BDD was four times longer in rats than in mice. Additional studies in rats showed the depletion of hepatic GSH and GSSG preceded the BDD-induced hypoglycemia and hepatotoxicity. Thus, the long half-life of BDD in rat plasma and the sustained depletion of hepatic GSH and GSSG may in part explain the higher sensitivity of the rat to BDD-induced hepatotoxicity. Furthermore, the results indicate BDD may play a role in BD-induced toxicity.
Accepted April 21, 2004
Systems Evaluation
Species and Tissue Differences in the Toxicity of 3-Butene-1,2-diol in Male Sprague-Dawley Rats and B6C3F1 Mice
2 Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, 53706
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  W. G. E. J. Schoonen, C. P. A. M. Kloks, J.-P. H. T. M. Ploemen, M. J. Smit, P. Zandberg, G. J. Horbach, J.-R. Mellema, C. Thijssen-vanZuylen, A. C. Tas, J. H. J. van Nesselrooij, et al. Uniform Procedure of 1H NMR Analysis of Rat Urine and Toxicometabonomics Part II: Comparison of NMR Profiles for Classification of Hepatotoxicity Toxicol. Sci., July 1, 2007; 98(1): 286 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.W. Powley, Y. Li, P.B. Upton, V.E. Walker, and J.A. Swenberg Quantification of DNA and hemoglobin adducts of 3,4-epoxy-1,2-butanediol in rodents exposed to 3-butene-1,2-diol Carcinogenesis, September 1, 2005; 26(9): 1573 - 1580. [Abstract] [Full Text] [PDF]
|
|