Aggravation of Galactosamine Hepatotoxicity by Albumin in Rats

Abstract

Abstract:The effect of rat albumin (RALB) on D-galactosamine (GalN) hepatotoxicity was investigated in male Crl:CD(SD) rats aged 6 weeks. The animals were divided into control, RALB, GalN, and RALB + GalN groups. GalN (800 mg/kg) was intraperitoneally administered immediately after an intravenous injection of RALB (100 mg/kg). The animals were euthanized 6 or 24 h later and subjected to laboratory investigations and histological examinations of the liver. Furthermore, in order to determine the contributing factors of the effect on the hepatotoxicity, intra-and intergroup comparisons were made between liver-injured and normal animals for parameters showing marked fluctuations at 6 h post-dosing. As a result, RALB induced fluctuations in many parameters, but no histological changes were observed in the liver at both 6 and 24 h. GalN induced mild or moderate hepatocyte necrosis (necrosis and/or apoptosis of hepatocytes) at 6 and 24 h, respectively, accompanied by increases in the serum ALT and AST levels. Concurrent administration of RALB with GalN markedly aggravated the GalN-induced hepatotoxicity, as shown by severe hepatocyte necrosis accompanied by further increases in the serum ALT, AST, and T-BIL levels in the surviving animals at 6 and 24 h, and by very severe hepatocyte necrosis with congestion in the dead animals. Moreover, serum tumor necrosis factor-α (TNF-α) level was also increased at 6 h in the RALB + GalN group, but not in the RALB or GalN alone groups. In conclusion, RALB was shown to aggravate GalN hepatotoxicity in rats, and the increased serum TNF-α level is considered to be a contributing factor of the aggravation. (J Toxicol Pathol 2008; 21: 175-183)

Correlation between synthesis of α2-macroglobulin as acute phase protein and degree of hepatopathy in rats

“…AST and ALT in rats administered a single dose of galactosamine at 1100 mg/kg are reported to be 100.86 and 121.57 U/mL, respectively [26]. AST and ALT in rats administered galactosamine at dose of 800 mg/kg are reported to be 96 and 199 U/ L, respectively [27]. AST and ALT showed higher values in this study than in hepatopathy model rats reported previously.…”