The reticuloendothelial system has been implicated in
galactosamine-induced liver injury because of a correlation between phagocytic alterations induced by colloidal
carbon or
endotoxin, and development of liver
necrosis. To evaluate this concept, the influence of
galactosamine on liver function and histology was determined in rats in which the reticuloendothelial system was normal, stimulated, or depressed.
Methyl palmitate was used as a reticuloendothelial system suppressant, and
glucan was used as a reticuloendothelial system activating agent. Administration of
galactosamine to control rats resulted in
hypoglycemia and increased serum
bilirubin concentration, elevated serum glutamic oxalacetic
transaminase, lactic
dehydrogenase and
glutamic pyruvic transaminase activities, and retention of
sodium sulfobromophthalein. Histological studies revealed hepatic
necrosis, and a polymorphonuclear and lymphocytic cellular infiltrate in
galactosamine-treated rats. Pretreatment of rats with
methyl palmitate inhibited
galactosamine-induced alterations in serum
glucose concentration, glutamic oxalacetic
transaminase and lactic
dehydrogenase activities, and
sodium sulfobromophthalein retention. Liver
necrosis and inflammatory reactions were also reduced in
methyl palmitate-treated
galactosamine-injected animals. In contrast, activation of the reticuloendothelial system by
glucan increased
galactosamine-induced alterations in serum
bilirubin,
glucose and
cholesterol concentrations, glutamic oxalacetic
transaminase, glutamic pyruvic transaminase and lactic
dehydrogenase activities, and
sodium sulfobromophthalein retention. Liver
necrosis and
inflammation were also increased. These findings suggest that the degree of
galactosamine-induced liver injury is directly correlated with macrophage function when specific macrophage-modifying agents are used.