Multiple
injections of D-
galactosamine induce
liver fibrosis and
cirrhosis in rats. The purpose of this immunopathological study was to correlate
inflammation and hepatic extracellular matrix remodeling after repeated administration of
galactosamine. Rats were given 10, 20, 30, 40, 60, 80, 100 and 140
intraperitoneal injections of D-
galactosamine (500 mg/kg body wt, three times weekly). Controls received
injections of
saline solution. Cryostat sections of liver tissue obtained on biopsy or autopsy were immunostained with a panel of monoclonal and polyclonal monospecific
antibodies reactive with macrophages, T and B lymphocytes,
desmin, the extracellular matrix components
fibronectin;
laminin;
collagen types I, III and IV; and the
fibronectin receptor alpha 5 beta 1. Total
RNA was extracted and Northern-blot analysis was performed with a specific
cDNA probe for rat
collagen type III. Spotty liver cell
necrosis and mild portal and parenchymal
inflammation was seen after 10
injections of
galactosamine. After 20 to 40
injections, expansion of protal tracts, prominent bile ductular proliferation and gradual formation of fibrous septa were encountered with the development of
cirrhosis at later intervals. These progressive histological changes were paralleled by a gradual increase of
desmin-positive cells in developing septa with deposition of
fibronectin;
collagen types I, III, and IV; and
laminin. Northern-blot analysis showed that this accumulation of extracellular matrix was not accompanied by increase of
mRNA for
collagen type III. In conclusion, repetitive administration of
galactosamine causes progressive
liver disease with prominent bile ductule proliferation and development of fibrous septa. These pathological alterations bear some resemblance to the morphological changes in chronic biliary disease in human beings.