抄録
The effect of adriamycin-oxidized dextran (ADM-OXD) on sinusoidal structure was studied using male Wistar rats. Ultramorphological monitoring and biochemical monitoring were performed after massive administration of ADM-OXD at a dose of 60mg/kg. Destruction of sinusoidal structure followed by damage to hepatocytes was subsequently observed. As early as 12 to 24 hours after ADM-OXD administration, endothelial cells and Kupffer cells were found to be degenerative or necrotic under transmission electron microscopic observation, and a tendency to disintegrate was observed in the sinusoidal wall structure. Scanning electron microscopic observation at 24 hours after administration revealed the destruction of the fenestral structure of endothelial cells, while morphological necrosis of hepatocytes and pronounced elevation of serum transaminase activity were noted at 48 hours. Mild endotoxemia was induced from soon after drug injection. In connection with this, serum complement activity began to decrease and was found to have fallen markedly at 24 hours, indicating significant consumption of alternative complement elements. ADM-OXD-induced hepatic dysfunction was found to be exacerbated by treatment with extrinsic lipopolysaccharide (LPS) and abated by treatment with endotoxin neutralizing agent (polymyxin B). Complement activity inhibitor also significantly abated hepatotoxicity. In situ liver perfusion of nitro bule tetrazolium (NBT) revealed that ADM-OXD administration did not produce stimulation of Kupffer cells. Anti-TNF-a treatment was found to have no abating effect on ADM-OXD-induced hepatic dysfunction. Biochemically, complement activation through endotoxemia may be assumed to participate in inducing hepatocyte damage, while mor-phologically, it is likely that destruction of the sinusoidal wall structure effects the susceptibility of hepatocytes to extrinsic environmental change.
