{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T20:14:04Z","timestamp":1772309644620,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2006,4,18]],"date-time":"2006-04-18T00:00:00Z","timestamp":1145318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background:\u2002<\/jats:bold> 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)\u2010treated rats. The present study investigated the relative contribution of NO synthase (NOS) isoforms on the severity of hepatic encephalopathy in TAA\u2010treated rats.<\/jats:p><jats:p><jats:bold>Method:\u2002<\/jats:bold> Fulminant hepatic failure was induced in male Sprague\u2010Dawley rats by intraperitoneal injection of TAA (350\u2003mg\/kg\/day) for 3\u2003days. Rats were divided into three groups to receive N<jats:sup>\u03c9<\/jats:sup>\u2010nitro\u2010L\u2010arginine methyl ester (L\u2010NAME, a non\u2010selective NOS inhibitor, 25\u2003mg\/kg\/day in tap water), L\u2010canavanine (an inducible NOS inhibitor, 100\u2003mg\/kg\/day via intraperitoneal injection) or normal saline (N\/S) from 2\u2003days prior to TAA administration and lasting for 5\u2003days. Severity of encephalopathy was assessed by the counts of motor activity. Plasma levels of tumor necrosis factor\u2010\u03b1 (TNF\u2010 \u03b1) were determined by enzyme\u2010linked immunosorbent assay (ELISA), and total bilirubin, alanine aminotransferase (ALT) and creatinine were determined by colorimetric assay.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Compared with L\u2010canavanine or N\/S\u2010treated rats (0% and 4%, respectively), the mortality rate was significantly higher in rats receiving L\u2010NAME administration (29%, <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.005). Inhibition of NO created detrimental effects on the counts of motor activities (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05). Rats treated with L\u2010NAME had significantly higher plasma levels of total bilirubin, ALT, creatinine and TNF\u2010 \u03b1 as compared with rats treated with L\u2010canavanine or N\/S (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.01).<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> Chronic L\u2010NAME administration, but not L\u2010canavanine, had detrimental effects on the severity of hepatic damage and motor activities in TAA\u2010treated rats. These results suggest that constitutive NOS activities play a major protective role in rats with fulminant hepatic failure.<\/jats:p>","DOI":"10.1111\/j.1440-1746.2006.04310.x","type":"journal-article","created":{"date-parts":[[2006,4,21]],"date-time":"2006-04-21T01:27:58Z","timestamp":1145582878000},"page":"1194-1199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Detrimental effects of nitric oxide inhibition on hepatic encephalopathy in rats with thioacetamide\u2010induced fulminant hepatic failure: Role of nitric oxide synthase isoforms"],"prefix":"10.1111","volume":"21","author":[{"given":"Chi\u2010Jen","family":"Chu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching\u2010Chih","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teh\u2010Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fa\u2010Yauh","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Full\u2010Young","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Chou","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Che\u2010Chang","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui\u2010Chun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun\u2010Sang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shou\u2010Dong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,6,16]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-7125(16)30639-3"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-206-43770"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/333664a0"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb14233.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840170116"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840200538"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1991.67"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.75.3.528"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(98)00052-5"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(95)80338-6"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(94)80091-X"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.2001.00775.x"},{"key":"e_1_2_6_14_2","first-page":"H1493","article-title":"Effect of angiotensin\u2010converting\u2010enzyme inhibition on bradykinin metabolism by vascular endothelial cells","volume":"264","author":"Grafe M","year":"1993","journal-title":"Am. 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