In:
Journal of Gastroenterology and Hepatology, Wiley, Vol. 21, No. 7 ( 2006-07), p. 1194-1199
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 N ω ‐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.
Type of Medium:
Online Resource
ISSN:
0815-9319
,
1440-1746
DOI:
10.1111/jgh.2006.21.issue-7
DOI:
10.1111/j.1440-1746.2006.04310.x
Language:
English
Publisher:
Wiley
Publication Date:
2006
detail.hit.zdb_id:
2006782-3
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