Increased Production of Nitric Oxide Mediates Selective Organ-Specific Effects of Endotoxin on Oxidative Stress

Author(s): Seyhan Sahan-Firat, Necmiye Canacankatan, Belma Korkmaz, Hatice Yildirim, Lulufer Tamer, C. Kemal Buharalioglu, A. Nihal Sari, Meltem Kacan, Demet Unsal, Bahar Tunctan

Journal Name: Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents)

Volume 11 , Issue 2 , 2012

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Endotoxemic shock is a systemic inflammatory response that is associated with increased nitric oxide (NO) production by inducible NO synthase (iNOS) which contributes to hypotension, vascular hyporeactivity, and multiple organ failure. Oxidative stress (OS) is a major contributing factor to high morbidity and mortality in endotoxemic shock. We have previously demonstrated that endotoxin-induced fall in blood pressure is associated with an increase in nitrite levels in serum, kidney, heart, thoracic aorta (TA), and superior mesenteric artery (SMA), a decrease in malondialdehyde (MDA) levels in the kidney, heart, TA, and SMA, and an increase in myeloperoxidase (MPO) activity in the heart and TA, but a decrease in the kidney and SMA of rats. In this study, we further investigated whether increased production of iNOS-derived NO contributes to endotoxin induced changes in the biomarkers of OS in the liver, lungs, brain, spleen, and femoral artery (FA) of rats. Endotoxin-induced increase in nitrite production was associated with a decrease in reduced glutathione levels in the liver, lungs, brain, spleen, and FA. MPO activity was increased by endotoxin in the lungs, spleen, and FA, but decreased in the liver and brain. MDA levels were increased by endotoxin in the lungs, brain, spleen, and FA, but were decreased in the liver. Activities of superoxide dismutase and catalase were decreased in the liver and spleen, but were increased in the lungs, brain, and FA. These effects of endotoxin were prevented by a selective iNOS inhibitor, phenylene-1,3-bis[ethane-2-isothiourea] dihydrobromide. These data suggest that iNOS-derived NO mediates selective organ-specific effects of endotoxin on OS.

Keywords: Endotoxemia, inducible NO synthase, inflammation, nitric oxide, oxidative stres, rat

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Article Details

Year: 2012
Page: [161 - 172]
Pages: 12
DOI: 10.2174/187152312803305740
Price: $65

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