title: Increased production of nitric oxide mediates selective organ-specific effects of endotoxin on oxidative stress.
abstract: 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.
authors.affiliation: Department of Pharmacology, Yenisehir Campus, Mersin University, Mersin, Turkey. seyhansahan06@gmail.com
authors.forename: Seyhan
authors.initials: S
authors.lastname: Sahan-Firat
authors.forename: Necmiye
authors.initials: N
authors.lastname: Canacankatan
authors.forename: Belma
authors.initials: B
authors.lastname: Korkmaz
authors.forename: Hatice
authors.initials: H
authors.lastname: Yildirim
authors.forename: Lulufer
authors.initials: L
authors.lastname: Tamer
authors.forename: C Kemal
authors.initials: CK
authors.lastname: Buharalioglu
authors.forename: A Nihal
authors.initials: AN
authors.lastname: Sari
authors.forename: Meltem
authors.initials: M
authors.lastname: Kacan
authors.forename: Demet
authors.initials: D
authors.lastname: Unsal
authors.forename: Bahar
authors.initials: B
authors.lastname: Tunctan
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D009928:Organ Specificity; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004731:Endotoxins; D009569:Nitric Oxide; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; D005978:Glutathione