Detrimental effects of nitric oxide inhibition on hepatic encephalopathy in rats with thioacetamide-induced fulminant hepatic failure: Role of nitric oxide synthase isoforms

Chi Jen Chu, Ching Chih Chang, Teh Fang Wang, Fa Yauh Lee*, Full Young Chang, Yi Chou Chen, Che Chang Chan, Hui Chun Huang, Sun Sang Wang, Shou Dong Lee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: Hepatic encephalopathy is a complex neuropsychiatric syndrome. A previous study showed that chronic nitric oxide (NO) inhibition aggravated the severity of encephalopathy in thioacetamide (TAA)-treated rats. The present study investigated the relative contribution of NO synthase (NOS) isoforms on the severity of hepatic encephalopathy in TAA-treated rats. Method: Fulminant hepatic failure was induced in male Sprague-Dawley rats by intraperitoneal injection of TAA (350 mg/kg/day) for 3 days. Rats were divided into three groups to receive Nω-nitro-L-arginine methyl ester (L-NAME, a non-selective NOS inhibitor, 25 mg/kg/day in tap water), L-canavanine (an inducible NOS inhibitor, 100 mg/kg/day via intraperitoneal injection) or normal saline (N/S) from 2 days prior to TAA administration and lasting for 5 days. Severity of encephalopathy was assessed by the counts of motor activity. Plasma levels of tumor necrosis factor-α (TNF- α) were determined by enzyme-linked immunosorbent assay (ELISA), and total bilirubin, alanine aminotransferase (ALT) and creatinine were determined by colorimetric assay. Results: Compared with L-canavanine or N/S-treated rats (0% and 4%, respectively), the mortality rate was significantly higher in rats receiving L-NAME administration (29%, P < 0.005). Inhibition of NO created detrimental effects on the counts of motor activities (P < 0.05). Rats treated with L-NAME had significantly higher plasma levels of total bilirubin, ALT, creatinine and TNF- α as compared with rats treated with L-canavanine or N/S (P < 0.01). Conclusion: Chronic L-NAME administration, but not L-canavanine, had detrimental effects on the severity of hepatic damage and motor activities in TAA-treated rats. These results suggest that constitutive NOS activities play a major protective role in rats with fulminant hepatic failure.

Original languageEnglish
Pages (from-to)1194-1199
Number of pages6
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume21
Issue number7
DOIs
StatePublished - Jul 2006

Keywords

  • Fulminant hepatic failure
  • Hepatic encephalopathy
  • Nitric oxide synthase isoforms
  • Thioacetamide

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