Hepatic encephalopathy in rats with thioacetamide-induced fulminant hepatic failure: role of endotoxin and tumor necrosis factor-alpha.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Chu
C J
CJ
Department of Medicine, Taipei Veterans General Hospital, National Yang-Ming University School of Medicine, Taiwan, ROC.
Chen
C T
CT
Wang
S S
SS
Lee
F Y
FY
Chang
F Y
FY
Lin
H C
HC
Wu
S L
SL
Lu
R H
RH
Chan
C C
CC
Huang
H C
HC
Lee
S D
SD
D000818:Animals; D004731:Endotoxins / Q000097:blood / Q000633:toxicity*; D006501:Hepatic Encephalopathy / Q000209:etiology*; D017093:Liver Failure / Q000150:complications* / Q000401:mortality; D008297:Male; D009043:Motor Activity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000633:toxicity*
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D013853:Thioacetamide