Liver Cirrhosis Research - Alcohol, Treatment, Drugs, Effects, Causes

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

Kang JS, Wanibuchi H, Morimura K, Puatanachokchai R, Salim EI, Hagihara A, Seki S, Fukushima S

Department of Pathology, Graduate School of Medicine, Osaka City University Medical School, Asahi-machi, Osaka 545-8585, Japan.

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 mug (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.

Published 13 April 2005 in Toxicol Sci, 85(1): 720-6.
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Liver Cirrhosis Research Today Archive:

Volume 1 (2004)
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Volume 2 (2005)
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