Restitutive response of Mini rat liver to injury induced by a single oral administration of thioacetamide.
Mini rats are a transgenic rat strain carrying antisense gene for rat growth hormone (GH), resulting in retarded growth and a lower blood GH level (136 +/- 42.0 ng/mL) compared with that of age-matched parental strain Wistar rats (329 +/- 337 ng/mL). Mini rats have been used by several investigators as a GH deficiency model. In this work, we gave a single oral administration of thioacetamide (TAA), a hepatotoxicant, to both Mini rats and Wistar rats to ascertain the influence of GH deficiency on liver response to chemically induced injury and subsequent regeneration. TAA administration caused liver injury in both strains, with a greater extent of injury in Mini rats. Proliferation of bile epithelial cells and so-called oval cells was prominent at Day 3 in Mini rats only, and this change correlated well with serum total bilirubin concentrations. Antibody against Ki-67 antigen revealed that cellular proliferation after TAA-induced liver injury was suppressed but prolonged in the Mini rat liver. Although hepatic stellate cells and Kupffer cells/macrophages were more abundant in the livers of TAA-treated Mini rats, the hepatic expression patterns of hepatocyte growth factor and transforming growth factor beta 1 were comparable to those of Wistar rats. Insulin-like growth factor-I gene expression was significantly reduced in the Mini rat liver. Our results imply that a lower GH level may exacerbate chemically induced liver injury, enhance infiltration/proliferation of non-parenchymal cells, suppress regeneration of hepatocytes, and induce proliferation of bile epithelial cells and oval cells when the liver is injured by TAA.
Medicinal Safety Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Y
Y
Tani
Y
Y
Kamai
K
K
Yamate
H
H
Mizuno
H
H
Yamamoto
T
T
Hosokawa
K
K
Doi
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D013006:Growth Hormone / Q000097:blood / Q000172:deficiency*; D017228:Hepatocyte Growth Factor / Q000235:genetics; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide / Q000633:toxicity*; D016212:Transforming Growth Factor beta / Q000235:genetics
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013853:Thioacetamide; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone