Hepatic encephalopathy in rats with thioacetamide-induced fulminant hepatic failure: role of endotoxin and tumor necrosis factor-alpha
Chu, C.J.; Chen, C.T.; Wang, S.S.; Lee, F.Y.; Chang, F.Y.; Lin, H.C.; Wu, S.L.; Lu, R.H.; Chan, C.C.; Huang, H.C.; Lee, S.D.
Zhonghua Yi Xue Za Zhi 64(6): 321-330
2001
ISSN/ISBN: 0578-1337 PMID: 11534799 Document Number: 538635
Hepatic encephalopathy, a complex neuropsychiatric syndrome secondary to acute liver failure, chronic parenchymal liver disease or portal-systemic shunting, may possibly develop through mediators of endotoxin and tumor necrosis factor-alpha (TNF-alpha). However, there are no published data concerning the relationships between the severity of encephalopathy and the plasma levels of endotoxin and TNF-alpha. Male Sprague-Dawley rats weighing about 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection ofthioacetamide (350 mg/kg/day) for 3 consecutive days. Severity of encephalopathy was assessed by measuring motor counts using an Opto-Varimex animal activity meter. Plasma levels of endotoxin and TNF-alpha were determined by chromogenic Limulus assay and ELISA method, respectively. Our study revealed that higher plasma levels of endotoxin (> 5.9 pg/ml) and TNF-alpha (> 18.8 pg/ml) were significantly associated with more blunted motor activities in rats with fulminant hepatic failure (p < 0.05). A significant correlation was observed between plasma concentrations of endotoxin and TNF-alpha (r = 0.59, p < 0.001). Plasma levels of endotoxin were weakly correlated with the total movements in an open field (r = -0.34, p = 0.032) and the counts of ambulatory (r = -0.38, p = 0.014) and vertical movements (r = -0.40, p = 0.010). There were no correlations between the motor counts and plasma levels of TNF-alpha (p > 0.05). In addition to endotoxin and TNF-alpha, other factors may participate in the pathogenesis of hepatic encephalopathy in rats with thioacetamide-induced fulminant hepatic failure.