Immunolpathology of Acute Galactosamine Hepatitis in Rats

Abstract

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. Injection 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 CD8-positive cells and were located in the portal tracts and parenchyma. CD4-positive 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.

Synaptophysin: A Novel Marker for Human and Rat Hepatic Stellate Cells

“…56 -59 Stimulation of sympathetic nerves was described as having a deteriorating effect on Gal hepatitis in rats. 60 Taken together with the evidence on the role of hepatic stellate cells in regeneration [1][2][3] and fibrosis, 4 -6 it is tempting to suggest that the central nervous system influences regeneration and fibrosis through hepatic stellate cells. The central nervous system could, for instance, influence the stellate cells' production of extracellular matrix components or the secretion of growth factors from stellate cells, with stellate cells functioning as the end organ effector cells of the central nervous system.…”

“…In addition , the presence of synaptic vesicles in stellate cell processes suggests a hitherto unknown mechanism of interaction with neighboring cells. Hepatic stellate cells have been demonstrated to be involved in conditions ranging from acute necrotizing and regenerating liver disorders [1][2][3] to chronic and fibrosing hepatic diseases. 4 -6 Essential functions exerted in these conditions are the production of extracellular matrix components, 7-9 the production of transforming growth factor ␤1 (TGF-␤1) 10,11 and hepatocyte growth factor (HGF), [12][13][14][15][16] and the role of effector cell responsible for microvascular tone regulation in the liver.…”

Human and Rat Hepatic Stellate Cells Express Neurotrophins and Neurotrophin Receptors

“…[24][25][26][27][28] On the other hand HSCs are known to proliferate and migrate towards areas of necrosis and areas of regeneration in varying pathologic conditions. [29][30][31] Finally, HSCs are contractile cells and are thought to be implicated in the regulation of microvascular tone in the liver. 32,33 HSCs express vimentin, desmin, ␣-smooth muscle actin (␣-SMA), [34][35][36][37][38][39] glial fibrillary acidic protein, [40][41][42] nestin, 42 neural cell adhesion molecule 43,44 and synaptophysin.…”

Intrahepatic Amino Acid and Glucose Metabolism in A D–Galactosamine-Induced Rat Liver Failure Model

“…44,51 It is noteworthy that D-galactosamine does not show a preferential target zone of damage along the hepatic acinus. 53 Because urea synthesis and glutamine synthesis are expressed in different regions of the hepatic acinus, 54 different results may be obtained when using hepatotoxins that exhibit regio-selectivity, such as acetaminophen. 55 Metabolic flux analysis, which balances the major input and output metabolites according to well-known stoichiometric constraints, was able to systematically identify pathway fluxes that were altered by D-galactosamine treatment.…”

“…23,24 We recently developed a mass-balance model to characterize changes in liver metabolism during the hypermetabolic response to injury. 25 Liver injury induced by D-galactosamine is morphologically similar to acute viral 26,27 or drug-induced 28 hepatitis in hu-mans, and it can produce hepatic encephalopathy or brain edema in animal models. [29][30][31] In a previous study, we characterized the survival and blood chemistry in D-galactosamineinduced hepatic failure in rats.…”