Enhancement by estradiol 3-benzoate in thioacetamide-induced liver cirrhosis of rats.
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.
Kang
Jin Seok
JS
Department of Pathology, Graduate School of Medicine, Osaka City University Medical School, Asahi-machi, Osaka 545-8585, Japan.
Wanibuchi
Hideki
H
Morimura
Keiichirou
K
Puatanachokchai
Rawiwan
R
Salim
Elsayed I
EI
Hagihara
Atsushi
A
Seki
Shuichi
S
Fukushima
Shoji
S
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D003094:Collagen / Q000378:metabolism; D000078842:Cytoglobin; D004195:Disease Models, Animal; D004357:Drug Synergism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010544:Peroxidases / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D011959:Receptors, Estradiol / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013853:Thioacetamide / Q000633:toxicity*
D000199:Actins; D003094:Collagen; D000078842:Cytoglobin; D004958:Estradiol; D010544:Peroxidases; D011959:Receptors, Estradiol; D013853:Thioacetamide; C000627268:Cygb protein, rat; C498862:Acta2 protein, rat; C074283:estradiol 3-benzoate