ToxSci Advance Access originally published online on February 16, 2005
Toxicological Sciences 2005 85(1):720-726; doi:10.1093/toxsci/kfi113
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Enhancement by Estradiol 3-Benzoate in Thioacetamide-Induced Liver Cirrhosis of Rats
* Department of Pathology and Department of Hepatology, Graduate School of Medicine, Osaka City University Medical School, Osaka 545-8585, Japan
Received December 17, 2004; accepted February 7, 2005
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 six 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.
Key Words: estradiol-3-benzoate; thioacetamide; cirrhosis; alpha-smooth muscle actin; Stellate cell activation-associated protein.