Role of macrophage function in galactosamine induced liver injury
Description
Correlations between phagocytic alterations induced by colloidal carbon or endotoxin, and the development of liver necrosis has implicated the reticuloendothelial system (RES) in galactosamine (GaIN) induced liver injury. In order to further evaluate this concept, the influence of GaIN on liver function and histology was ascertained in rats in which the RES was either normal, stimulated or depressed. Methyl palmitate or glucan were employed as selective RES suppressant or activating agents, respectively. Biochemical and histological profiles and endotoxemia were studied 24 hours following intraperitoneal administration of GaIN (lg/kg) in either control, glucan or methyl palmitate-treated rats. Biochemical profiles included: serum glucose, phosphorus, total bilirubin, urea nitrogen, uric acid, total protein, albumin, globulin, cholesterol, alkaline phosphatase, glutamic oxalacetic transaminase (SGOT), lactic dehydrogenase (LDH), glutamic pyruvic transaminase (SGPT), creatinine phosphokinase (CPK), triglyceride, plasma electrolytes, and plasma sodium sulfobromphthalein (BSP) retention The Limulus Lysate Gelation Test (LGT) was employed for the quantitative determination of endotoxemia in control, glucan, methyl palmitate and GaIN-treated rats and in rats undergoing combined procedures Administration of GaIN to control rats resulted in significant elevations in SGOT, total bilirubin, urea nitrogen, and profound plasma retention of BSP. Hypoglycemia and hypoglobulinemia were also observed. Histological studies denoted hepatic necrosis with, a polymorphonuclear and, lymphocytic cellular infiltrate in GaIN-treated rats Pretreatment of rats with intravenously administered methyl palmitate (2g/kg) to induce macrophage dysfunction prevented GaIN induced alterations in the serum glucose, SGOT, LDH, and BSP. Liver necrosis and inflammatory reactions were also significantly reduced in methyl palmitate-GaIN-treated animals In contrast, RES activation with intravenously administered glucan (10 mg/kg) on days (-7 & -3), enhanced GaIN-induced alterations in serum bilirubin, glucose, cholesterol, SGOT, SGPT, LDH and BSP. Liver necrosis and inflammation were also significantly enhanced Endotoxemia was not detected in any of the rats regardless of treatment or time following GaIN, methyl palmitate or glucan administration. These composite findings denote that GaIN hepatitis need not be inversely correlated to macrophage functional status, but may be directly correlated when specific macrophage modifying agents such as glucan and methyl palmitate are employed