Skip Navigation



ToxSci Advance Access published online on July 28, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh232
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
82/1/318    most recent
kfh232v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Richards, V. E.
Right arrow Articles by McQueen, C. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Richards, V. E.
Right arrow Articles by McQueen, C. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received May 12, 2004
Accepted July 23, 2004

Systems Toxicology

Hepatic Gene Expression and Lipid Homeostasis in C57Bl/6 Mice Exposed to Hydrazine or Acetylhydrazine

Victoria E. Richards 1, Binh Chau 1, M. Randy White 2, Charlene A. McQueen 1*

1 Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85721
2 PRI, Mt. Vernon, Pathology, Evansville, IN 47721

* To whom correspondence should be addressed. E-mail: mcqueen{at}pharmacy.arizona.edu.


  Abstract

Hydrazine (HD) and acetylhydrazine (AcHD) are metabolites of the antituberculosis drug isoniazid (INH) that have been implicated in INH-induced liver damage. The hepatotoxicity of AcHD and HD were compared in adult male C57Bl/6J mice by evaluating hepatic histopathology, plasma biochemistry, and hepatic gene expression. By all measures, HD had significantly greater effects than AcHD. There was no evidence of liver damage following exposure to AcHD (300 mg/kg, po). However, HD at this dose caused marked hepatic necrosis, macrovesicular degeneration and steatosis. Lipid accumulation was initiated 2 h after HD exposure with hepatic macrovesicular degeneration evident after 4 h and severe necrosis by 36 h. Gene expression profiles were compared 24 h following 100 mg/kg po of HD or AcHD. HD changed the hepatic expression of more genes than AcHD, particularly lipid synthesis, transport and metabolism genes that may be involved in steatosis. Hepatic expression of genes regulated by peroxisome proliferator activated receptors (PPAR) and sterol regulatory element binding protein (SREBP) transcription factors was increased only by HD. The hepatotoxicty and hepatic gene expression profile of HD, but not AcHD, indicate that exposure to HD initiates a process whereby the production and intracellular transport of hepatic lipids is favored over the removal of fatty acids and their metabolites.

Keywords: hydrazine; acetylhydrazine; cDNA microarray; steatosis; hepatotoxicity; peroxisome proliferator-activated receptor.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J R Soc InterfaceHome page
P. J. Ballester, I. Westwood, N. Laurieri, E. Sim, and W. G. Richards
Prospective virtual screening with Ultrafast Shape Recognition: the identification of novel inhibitors of arylamine N-acetyltransferases
J R Soc Interface, July 8, 2009; (2009) rsif.2009.0170v1.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
H.-Q. Yin, M. Kim, J.-H. Kim, G. Kong, M.-O. Lee, K.-S. Kang, B.-I. Yoon, H.-L. Kim, and B.-H. Lee
Hepatic Gene Expression Profiling and Lipid Homeostasis in Mice Exposed to Steatogenic Drug, Tetracycline
Toxicol. Sci., November 1, 2006; 94(1): 206 - 216.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.