title: Enhancement by estradiol 3-benzoate in thioacetamide-induced liver cirrhosis of rats.
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 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.
authors.affiliation: Department of Pathology, Graduate School of Medicine, Osaka City University Medical School, Asahi-machi, Osaka 545-8585, Japan.
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Kang
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
authors.forename: Keiichirou
authors.initials: K
authors.lastname: Morimura
authors.forename: Rawiwan
authors.initials: R
authors.lastname: Puatanachokchai
authors.forename: Elsayed I
authors.initials: EI
authors.lastname: Salim
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hagihara
authors.forename: Shuichi
authors.initials: S
authors.lastname: Seki
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
mesh_terms: 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*
chemical_list: 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