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Title: Increased formation of S-nitrothiols and nitrotyrosine in cirrhotic rats during endotoxemia
Authors: Ottesen, L.H.
Harry, D.
Frost, M.
Davies, S.
Khan, K.
Halliwell, B. 
Moore, K.
Keywords: Bile duct ligation
Experimental study
Free radicals
Issue Date: 2001
Citation: Ottesen, L.H., Harry, D., Frost, M., Davies, S., Khan, K., Halliwell, B., Moore, K. (2001). Increased formation of S-nitrothiols and nitrotyrosine in cirrhotic rats during endotoxemia. Free Radical Biology and Medicine 31 (6) : 790-798. ScholarBank@NUS Repository.
Abstract: Plasma S-nitrosothiols are believed to function as a circulating form of nitric oxide that affects both vascular function and platelet aggregation. However, the formation of circulating S-nitrosothiols in relation to acute and chronic disease is largely unknown. Plasma S-nitrosothiols were measured by chemiluminescence in rats with biliary cirrhosis or controls, and the effect of lipopolysaccharide (LPS) on their formation was determined. Plasma S-nitrosothiols were increased in rats with cirrhosis (206 ± 59 nM) compared to controls (51 ± 6 nM, p < .001). Two hours following injection of LPS (0.5 mg/kg) plasma S-nitrosothiols increased to 108 ± 23 nM in controls (p < .01) and to 1335 ± 423 nM in cirrhotic rats (p < .001). The plasma clearance and half-life of S-nitrosoalbumin, the predominant circulating S-nitrosothiol, were similar in control and cirrhotic rats, confirming that the increased plasma concentrations were due to increased synthesis. Because reactive nitrogen species, such as peroxynitrite, may cause the formation of S-nitrosothiols in vivo, we determined the levels of nitrotyrosine by gas chromatography/mass spectrometry as an index for these nitrating and nitrosating radicals. Hepatic nitrotyrosine levels were increased at 7.0 ± 1.2 ng/mg in cirrhotic rats compared to controls (2.0 ± 0.2 ng/mg, p < .01). Hepatic nitrotyrosine levels increased by 2.3-fold and 1.5-fold in control and cirrhotic rats, respectively, at 2 h following injection of LPS (p < .01). Strong positive staining for nitrotyrosine was shown by immunohistochemistry in all the livers of the rats with cirrhosis. We conclude that there is increased formation of S-nitrosothiols and nitrotyrosine in biliary cirrhosis, and this is markedly upregulated during endotoxemia. © 2001 Elsevier Science Inc.
Source Title: Free Radical Biology and Medicine
ISSN: 08915849
DOI: 10.1016/S0891-5849(01)00647-5
Appears in Collections:Staff Publications

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