Poly(adp-Ribose) Synthetase Inhibition Prevents Lipopolysaccharide-Induced Peroxynitrite Mediated Damage in Diaphragm

Özdülger, Ali; Cinel, İsmail; Ünlü, Ali; Cinel, Leyla; Mavioglu, Ilhan; Tamer, Lülüfer; Atik, Uğur; Oral, Uğur

doi:10.1016/s1043-6618(02)00037-3

Cited by 16 publications

(11 citation statements)

References 34 publications

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“…In the present study, LPS induced multiple organ oxidative damages (heart, kidney, spleen) characterized by increased MDA concentration. These results were in agreement with previous studies, which reported increased MDA concentrations in the serum, liver, kidney, heart and diaphragmatic muscle (Portoles et al, 1993;Zheng et al, 2000;Ozdulger et al, 2002;Keskin et al, 2005). In the studies associated with antioxidants such as SOD, GPX, CAT and GSH, when only antioxidants are evaluated, conflicting results were reported.…”

Section: Discussionsupporting

confidence: 91%

Effect of flunixin meglumin on the antioxidant status in endotoxemia

Konyalιoğlu¹,

Er²,

Üney³

et al. 2007

Acta vet. (Beogr.)

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In this study, the effects of flunixin meglumin on the antioxidant status during endotoxemia were investigated. Thirty Balb/C mice were divided into three equal groups. Mice with no treatment formed the control group (group I). Mice treated with lipopolysaccharide (LPS) and LPS + flunixin meglumin (FM) formed groups II and III, respectively. All mice were sacrificed and tissue samples were collected 6 hours after treatments. Activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), as well as levels of malondialdehyde (MDA) and glutathione (GSH) were determined spectrophotometrically. LPS caused a significant (p<0.05) increase in levels of MDA (heart, kidney, spleen) which is an accepted biomarker of oxidative stress, and changed the levels of SOD, GPX, CAT and GSH. When FM was administered simultaneously with LPS, FM inhibited (p<0.05) the increase of MDA levels in all tissues. As results, LPS caused MDA levels and oxidative stress to increase. However, FM depressed the LPS induced increase of MDA levels. This antioxidant effect of FM may be beneficial in endotoxemia

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Section: Discussionsupporting

confidence: 91%

Effect of flunixin meglumin on the antioxidant status in endotoxemia

Konyalιoğlu¹,

Er²,

Üney³

et al. 2007

Acta vet. (Beogr.)

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“…Indeed, it has been extensively reported that sepsis induces peroxynitrite formation. For example, increased levels of 3-nitrotyrosine have been detected in skeletal muscle, lung, liver, kidney, and gut in animal models of sepsis (1,4,9,31,38,45). In humans, plasma 3-nitrotyrosine levels are undetectable in normal subjects but rise as high as 118 Ϯ 22 M in septic patients (17).…”

Section: Discussionmentioning

confidence: 99%

Ascorbate protects against vascular leakage in cecal ligation and puncture-induced septic peritonitis

Zhou

Kamenos

Pendem

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Vascular leakage in multiple organs is a characteristic pathological change in sepsis. Our recent study revealed that ascorbate protects endothelial barrier function in microvascular endothelial cell monolayers through inhibiting serine/threonine protein phosphatase 2A (PP2A) activation (Han M, Pendem S, Teh SL, Sukumaran DK, Wu F, Wilson JX. Free Radic Biol Med 48: 128-135, 2010). The present study addressed the mechanism of protection by ascorbate against vascular leakage in cecal ligation and puncture (CLP)-induced septic peritonitis in mice. CLP caused NADPH oxidase activation and endothelial nitric oxide synthase (eNOS) uncoupling to produce superoxide, increased NO production by inducible NOS (iNOS) and neuronal NOS (nNOS) activity, and elevated 3-nitrotyrosine (a product of peroxynitrite) formation and PP2A activity in the hindlimb skeletal muscles at 12 h after CLP. The increase in PP2A activity was associated with decreased levels of phosphorylated serine and threonine in occludin, which was immunoprecipitated from freshly harvested endothelial cells of the septic skeletal muscles. Moreover, CLP increased the vascular permeability to fluorescent dextran and Evans blue dye in skeletal muscles. An intravenous bolus injection of ascorbate (200 mg/kg body wt), given 30 min prior to CLP, prevented eNOS uncoupling, attenuated the increases in iNOS and nNOS activity, decreased 3-nitrotyrosine formation and PP2A activity, preserved the phosphorylation state of occludin, and completely inhibited the vascular leakage of dextran and Evans blue. A delayed ascorbate injection, given 3 h after CLP, also prevented the vascular permeability increase. We conclude that ascorbate injection protects against vascular leakage in sepsis by sequentially inhibiting excessive production of NO and superoxide, formation of peroxynitrite, PP2A activation, and occludin dephosphorylation. Our study provides a scientific basis for injection of ascorbate as an adjunct treatment for vascular leakage in sepsis.

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“…Sepsis-induced neutrophil-mediated tissue injury has been demonstrated in a variety of organs including the lungs (84 -86), diaphragm (87), kidneys (86), intestine (88,89), and liver (86). Sepsis-induced neutrophil-mediated tissue injury has been demonstrated in a variety of organs including the lungs (84 -86), diaphragm (87), kidneys (86), intestine (88,89), and liver (86).…”

Section: Neutrophils and Monocyte/macrophages In Inflammationmentioning

confidence: 99%