Role of free nitrogen and oxygen radicals in the pathogenesis of lipopolysaccharide-induced endotoxemia

Sanikidze, Т; Tkhilava, N. G.; Papava, M; Datunashvili, I; Gongadze, M. T.; Gamrekelashvili, D. D.; Bakhutashvili, V I

doi:10.1007/s10517-006-0130-3

Cited by 12 publications

(10 citation statements)

References 11 publications

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“…We also measured 3-NT levels in spleen tissues by HPLC method to investigate the ONOO --mediated damage mechanism after endotoxin administration at 6 th h, and determined that 3-NT levels increased during endotoxemia. These results indicated that LPS administration resulted in activation of macrophages in the spleen to produce reactive oxygen and nitrogen species [1,32,33]. When released in vivo into biological fluids, NO is autooxidized to NO 2 -and NO 3 -.…”

Section: Discussionmentioning

confidence: 89%

“…The reaction product, ONOO -, is a powerful oxidant and cytotoxic species [8]. ONOO -is known to be capable of leading to nitration of tyrosine residues, and nitrotyrosine is a specific biomarker of ONOO -generation [2,5,33]. Bian and Murad [1] investigated that the distrubution of nitrotyrosine in spleen, lung and liver, all of which are rich in macrophages and endothelial cells in LPS-treated rats, and they showed that the density of some nitrated proteins was significantly enhanced after LPS treatment by immunublotting and immunohistochemical methods.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Taurine on Nitric Oxide and 3-Nitrotyrosine Levels in Spleen During Endotoxemia

et al. 2011

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Taurine (2-aminoethanesulfonic acid) is a free sulfur-containing β-amino acid which has antioxidant, antiinflammatory and detoxificant properties. In the present study, the role of endotoxemia on peroxynitrite formation via 3-nitrotyrosine (3-NT) detection, and the possible antioxidant effect of taurine in lipopolysaccharide (LPS)-treated guinea pigs were aimed. 40 adult male guinea pigs were divided into four groups; control, endotoxemia, taurine and taurine+endotoxemia. Animals were administered taurine (300 mg/kg), LPS (4 mg/kg) or taurine plus LPS intraperitoneally. After 6 h of incubation, when highest blood levels of taurine and endotoxin were attained, the animals were sacrificed and spleen samples were collected. The amounts of 3-nitrotyrosine and taurine were measured by HPLC, and reactive nitrogen oxide species (NOx) which are stable end products of nitric oxide was measured spectrophotometrically in spleen tissues. LPS administration significantly decreased the concentration of taurine whilst increased levels of 3-NT and NOx compared with control group. It was determined that taurine treatment decreased the levels of 3-nitrotyrosine and NOx in taurine+endotoxemia group. The group in which taurine was administered alone, contradiction to well-known antioxidant effect, taurine caused elevated concentration of 3-NT and NOx. This data suggest that taurine protects spleen against oxidative damage in endotoxemic conditions. However, the effect of taurine is different when it is administered alone. In conclusion, taurine may act as an antioxidant during endotoxemia, and as a prooxidant in healthy subjects at this dose.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Effects of Taurine on Nitric Oxide and 3-Nitrotyrosine Levels in Spleen During Endotoxemia

et al. 2011

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“…So far, the mechanisms of this effect are unclear. Plaferon-LB is thought to rehabilitate the electron transport at the sites of the I and IV complexes of mitochondrial chain and leads to a decrease in the production of free radicals and the normalization of a cell's redox status [15,16]. Intensive experimental and clinical studies have revealed significant beneficial preventive effects of Plaferon-LB in models of cardiac infarction and global cerebral ischemia [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Treatment of Cerebral Infarction: An Experimental Study

Sanikidze

Beridze

Mitagvaria³

et al. 2012

International Journal of Neuroscience

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We investigated the effect of the amniotic-derived peptide Plaferon-LB on cerebral tissue damage during photochemical insults in rats. Plaferon-LB (US patent number: 20070123467 A1) was extracted from the amniochorionic membrane of a human placenta and showed a relatively strong antihypoxic effect compared to other interferon. Thrombotic infarction was induced by photochemical illumination after intravenous injection of Rose Bengal. The infarct volume, cerebral tissue oxygen tension, cerebral blood flow, and capillary damage were measured in the following groups: untreated control rats, Plaferon-LB-alone rats, insult-alone rats, and insult in Plaferon-LB pretreated rats. The technique of electron paramagnetic resonance (EPR) spectroscopy was used to study free-radical metabolites in the blood and brain tissue ex vivo. Plaferon-LB alone had no effect on systemic blood pressure, cerebral blood flow, and reactive metabolites in the brains of intact animals. In the insult-alone group, a focal hemorrhage was observed in the ischemic area. The cerebral blood flow and tissue oxygen pressure declined to zero within an hour and remained at this level throughout the insult. The treatment with Plaferon-LB 0.5 hr before illumination resulted in a significant reduction of the median infarct size in the insult-alone group. The total length and percentage ratio of thrombotic vessels were significantly diminished in the infarct area. The intensity of Fe2+, Mn2+ -, Mo5+ -xanthinoxidase-containing complexes, and nitric oxide EPR signals was decreased, and the electron transport in the mitochondria was normalized. The results indicate a significant beneficial effect of Plaferon-LB on cerebral infarct, which is likely due to its antioxidative properties.

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“…Oxidant stress plays a major role in septic shock and systemic inflammatory response syndrome (SIRS) [1,2]. The generation of reactive nitrogen and oxygen species increased in lipopolysaccharide-induced endotoxaemia in mice [3]. These changes contributed to the dysfunction of the mitochondrial electron transport chain and the development of oxidative stress [3].…”

Section: Introductionmentioning

confidence: 99%

“…The generation of reactive nitrogen and oxygen species increased in lipopolysaccharide-induced endotoxaemia in mice [3]. These changes contributed to the dysfunction of the mitochondrial electron transport chain and the development of oxidative stress [3]. Sepsis represents a dysregulated innate immune response to an offending pathogen.…”

Section: Introductionmentioning

confidence: 99%

Polymyxin B-immobilized fibre haemoperfusion reduces urinary 8-hydroxy-2'-deoxyguanosine levels in patients with septic shock

Nakamura¹,

Kawagoe²,

Ueda³

et al. 2006

TCIC

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Objective. To determine whether urinary 8-hydroxy-2?-deoxyguanosine (8-OHdG) levels are altered in patients with septic shock and whether polymyxin B-immobilized fibre (PMX-F) haemoperfusion reduces the 8-OHdG level in these patients. Design and subjects. Twenty patients with septic shock and 20 age-matched healthy volunteers were included in the study. The septic shock patients were divided into two treatment groups: a PMX-F treatment group (n 012) and a non-PMX-F treatment group (n08). Standard supportive care was continued without change during PMX-F haemoperfusion. Clinical markers, including plasma endotoxin, were measured before and after the first and the second PMX-F treatment and the following day. Urinary 8-OHdG levels were also examined before and after the first and the second PMX-F treatment (24 h pooled urine) and the following day. Results. Urinary 8-OHdG levels were significantly higher in septic shock patients (median 38.0 ng/mg creatinine; range 16.0Á52.0 ng/mg creatinine) than in healthy volunteers (5.5 ng/mg creatinine; range 4.5Á7.5 ng/mg creatinine) (pB0.01). Urinary 8-OHdG levels correlated significantly with plasma endotoxin levels (pB 0.01), the Acute Physiology and Chronic Health Evaluation score (pB0.01) and the Sepsis-related Organ Failure Assessment score (pB0.01). PMX-F haemoperfusion reduced the plasma endotoxin and urinary 8-OHdG levels significantly after the first (p B0.01) and the second treatment (pB0.001) and the following day (pB0.001). However, these markers did not change significantly with non-PMX treatment. Conclusions. An increased urinary 8-OHdG level appears to be associated with septic shock, and PMX-F haemoperfusion is effective in reducing urinary 8-OHdG levels in patients with septic shock.

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Role of free nitrogen and oxygen radicals in the pathogenesis of lipopolysaccharide-induced endotoxemia

Cited by 12 publications

References 11 publications

Effects of Taurine on Nitric Oxide and 3-Nitrotyrosine Levels in Spleen During Endotoxemia

Effects of Taurine on Nitric Oxide and 3-Nitrotyrosine Levels in Spleen During Endotoxemia

Neuroprotective Treatment of Cerebral Infarction: An Experimental Study

Polymyxin B-immobilized fibre haemoperfusion reduces urinary 8-hydroxy-2'-deoxyguanosine levels in patients with septic shock

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