Immunohistochemical study on galactosamine-induced subacute hepatitis in rats of JCL: Wistar-TGN (ARGHGEN) 1 Nts strain (Mini rats).

Immunohistochemical study was carried out on D-galactosamine hydrochloride (GaIN)-induced subacute hepatitis in rats of JCL: Wistar-TGN (ARGHGEN) 1Nts strain (Mini rats), in which the expression of growth hormone gene is suppressed by the presence of an antisense transgene. Mini rats were given 1000 mg/kg of GaIN once a week for 4 consecutive weeks and killed at 1, 2, 3 and 4 weeks after the first administration. At 1 week after the first administration, proliferation of small epithelial cells positive for both alpha-fetoprotein and cytokeratin 7, i.e. so-called oval cells, was observed in the whole area of each hepatic lobule, and prominent deposition of fibronectin, laminin and type IV collagen was detected around these oval cells. Together with these extracellular matrix components, many activated Ito cells positive for both desmin and alpha-smooth muscle actin were observed. With time, most of the oval cells formed duct-like structures and lost their positive stainability for alpha-fetoprotein, and many Ito cells became inactive. Deposition of fibronectin decreased rapidly from 2 weeks after the first administration. At 4 weeks after the first administration, deposition of laminin was detected only around the duct-like structures, where that of type IV collagen was also still prominent. These results suggest that a large population of oval cells differentiated into bile duct epithelial cells and that Ito cells and extracellular matrix components might play a role in this process.