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ToxSci Advance Access published online on February 16, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi113
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Toxicological Sciences © The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received December 17, 2004
Accepted February 7, 2005

Systems Toxicology

Enhancement by estradiol 3-benzoate in thioacetamide-induced liver cirrhosis of rats

Jin Seok Kang 1, Hideki Wanibuchi 1, Keiichirou Morimura 1, Rawiwan Puatanachokchai 1, Elsayed I. Salim 1, Atsushi Hagihara 1, Shuichi Seki 2, and Shoji Fukushima 1*

1 Department of Pathology, Osaka City University Medical School
2 Department of Hepatology, Graduate School of Medicine, Osaka City University Medical School

* To whom correspondence should be addressed.
Shoji Fukushima, E-mail: fukuchan{at}med.osaka-cu.ac.jp


  Abstract

As part of an investigation on the role of estrogen in liver disease, we tested the effects of estradiol-3-benzoate (EB) in the thioacetamide (TAA)-induced rat liver cirrhosis model. Male F344 rats (n=100) were divided into 6 groups. Animals of groups 1-4 received TAA (0.03% in drinking water) for 12 weeks, and groups 5 and 6 served as controls without TAA. For the exposure period, EB pellets were implanted subcutaneously to give doses of 0 (groups 1 and 5), 1 (group 2), 10 (group 3) and 100 µg (groups 4 and 6) simultaneously. All animals were sacrificed at week 12. Significant increase of liver cirrhosis, liver weight, collagen content and lipid peroxidation in the livers was evident in groups 3 and 4 (p<0.05) compared with group 1. Formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was significantly elevated in group 4 (p<0.01), along with expression of alpha-smooth muscle actin (alpha-SMA) and stellate cell activation-associated protein (STAP), as determined by RT-PCR analysis (p<0.01). However, there were no differences in liver weight, collagen content, lipid peroxidation, 8-OHdG formation, and alpha-SMA and STAP mRNA expression between groups 5 and 6. We conclude that EB treatment enhances TAA-induced cirrhosis, associated with increase of oxidative stress and activation of hepatic stellate cells.

Keywords: Estradiol-3-benzoate (EB); Thioacetamide (TAA); Cirrhosis; Alphasmooth muscle actin (alpha-SMA); Stellate cell activation-associated protein (STAP).
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