IMMUNOHISTOCHEMICAL STUDY OF HEPATIC-FIBROSIS INDUCED IN RATS BY MULTIPLE GALACTOSAMINE INJECTIONS

Multiple injections of D-galactosamine induce liver fibrosis and cirrh osis in rats. The purpose of this immunopathological study was to corr elate inflammation and hepatic extracellular matrix remodeling after r epeated administration of galactosamine. Rats were given 10, 20, 30, 4 0, 60, 80, 100 and 140 intraperitoneal injections of D-galactosamine ( 500 mg/kg body wt, three times weekly). Controls received injections o f saline solution. Cryostat sections of lives tissue obtained on biops y or autopsy were immunostained with a panel of monoclonal and polyclo nal monospecific antibodies reactive with macrophages, T and B lymphoc ytes, desmin, the extracellular matrix components fibronectin; laminin ; collagen types I, III and IV; and the fibronectin receptor alpha 5 b eta 1. Total RNA was extracted and Northern-blot analysis was performe d with a specific cDNA probe for rat collagen type III. Spotty liver c ell necrosis and mild portal and parenchymal inflammation was seen aft er 10 injections of galactosamine. After 20 to 40 injections, expansio n of portal tracts, prominent bile ductular proliferation and gradual formation of fibrous septa were encountered with the development of ci rrhosis at later intervals. These progressive histological changes wer e Paralleled by a gradual increase of desmin-positive cells in develop ing septa with deposition of fibronectin; collagen types I, III and IV ; and Iaminin. Northern-blot analysis showed that this accumulation of extracellular matrix was not accompanied by increase of mRNA for coll agen type III. In conclusion, repetitive administration of galactosami ne causes progressive liver disease with prominent bile ductule prolif eration and development of fibrous septa. These pathological alteratio ns bear some resemblance to the morphological changes in chronic bilia ry disease in human beings.