Galactosamine hydrochloride induces liver disease in rats that morphologically resembles drug-induced hepatitis in man. In this study we analyzed the character of the inflammatory reaction following the toxic damage resulting from the administration of galactosamine hydrochloride using a broad panel of monoclonal antibodies to lymphocyte subsets and macrophages. Fat-storing cells were identified with a polyclonal anti-desmin antibody. Cellular proliferation was assessed by labeling S-phase cells with the thymidine analog bromodeoxyuridine. Iqjection of galactosamine hydrochloride was associated with conspicuous hepatocyte necrosis and parenchymal granulocyte influx in the first 24 hr. Thereafter, mononuclear inflammatory cells predominated, mainly T lymphocytes and macrophages, with maximal numbers at 48 hr. The majority of T lymphocytes were CDS-positive cells and were located in the portal tracts and parenchyma. CD4positive T cells were scarce and confined to the portal tracts. Proliferation of fat-storing cells paralleled hepatocyte regeneration with maximal values after 48 to 72 hr.
The temporal relationship between infiltrating mononuclear cells, mainly T lymphocytes of CD8 phenotype and macrophages, fat-storing cell proliferation and hepatic regeneration suggests pathophysiological interactions between these cell types in liver injury in the rat after galactosamine hydrochloride administration. (HEPATOLOGY 1990;11:622-627.) In rats, a single injection of D-galactosamine hydrochloride (Gal-NH,) induces liver disease that morphologically resembles drug-induced hepatitis in man, with spotty hepatocyte necrosis and prominent portal and parenchymal inflammation. After its initial description in the 60s, a body of literature has emerged on this experimental model (1). Biochemical studies have indicated a direct relationship between hepatic cell death and depletion of uridine nucleotides, the development of liver cell membrane defects and alterations in the synthesis and secretion of plasma lipoproteins (1-5). Altered reticuloendothelial system function and endotoxemia are known to contribute to the development of ~ ~