Role of Induced Nitric Oxide in the Initiation of the Inflammatory Response After Postischemic Injury

Cuzzocrea, Salvatore; Chatterjee, Prabal K.; Mazzon, Emanuela; Dugo, Laura; Sarro, Angela De; Loo, Fons A. J. van de; Caputi, Achille P.; Thiemermann, Christoph

doi:10.1097/00024382-200208000-00014

Cited by 118 publications

(84 citation statements)

References 28 publications

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“…It is noteworthy that one study in which iNOS knockout mice were used and reperfusion was not performed (similar to our protocol) found that injury was severe and angiogenesis in the chronic stage was augmented [45]. This is consistent with our results, and indicates that reperfusion plays a critical role in the outcome [46].…”

Section: Discussionsupporting

confidence: 90%

Biphasic Action of Inducible Nitric Oxide Synthase in a Hindlimb Ischemia Model

Kimura

Goto

Yagi

et al. 2006

J. Clin. Biochem. Nutr.

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Summary We investigated the influence of inducible nitric oxide synthase (iNOS) on acute ischemic injury and chronic angiogenesis. In a hindlimb ischemia model, NO produced by endothelial NO synthase (eNOS) reduces ischemic injury and promotes angiogenesis. However, the effect of the large amounts of NO generated by induced iNOS is unclear. Experimental groups of mice were as follows: (1) wild-type group (Wild), (2) iNOS-knockout group (iNOS-KO), and (3) aminoguanidine-treated wild-type group (Wild + AG), which received aminoguanidine from day 0 to day 3 after ischemia. Acute ischemic injury was evaluated by measuring the plasma CK value and ischemic score. Chronic angiogenesis was evaluated by microangiography and with a non-contact type Doppler blood flowmeter on day 3. Compared with the Wild group (251 ± 34.7 IU/l), the CK value was significantly elevated in the iNOS-KO (497 ± 126.7 IU/l) and Wild + AG (587.2 ± 128.7 IU/l) groups. The ischemic score was significantly increased in the iNOS-KO (92%) and Wild ± AG (66.6%) groups compared with the Wild group (23%). Blood flow was significantly increased in the iNOS-KO group (58.7 ± 15.3%) compared with the Wild (38.1 ± 15.9%) and Wild ± AG (43.5 ± 9.8%) groups in the chronic stage. Microangiography revealed a significantly increased number of blood vessels in the iNOS-KO (0.29 ± 0.02) group compared with the Wild (0.12 ± 0.01) and Wild + AG (0.15 ± 0.02) groups. Our findings indicate that NO generated by iNOS has a biphasic action, reducing acute ischemic injury and inhibiting angiogenesis in the chronic stage.

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Section: Discussionsupporting

confidence: 90%

Biphasic Action of Inducible Nitric Oxide Synthase in a Hindlimb Ischemia Model

Kimura

Goto

Yagi

et al. 2006

J. Clin. Biochem. Nutr.

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“…Although NO produced through constitutive NO synthase can be an important protective molecule for the small intestine at the onset of intestinal I/R, 15 over-production of NO through the inducible NO synthase (iNOS), especially under the circumstance of oxidant stress, may prove detrimental. The tight positive correlation between Chiu's score and NO production ( Figure 2D) is consistent with the notion that over-production of NO could be detrimental.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that over-production of nitric oxide (NO) in intestinal mucosa tissue following intestinal I/R can aggravate lipid oxidative damage 14,15 and that an increase of endothelin-1 (ET-1) is involved in the pathogenesis of intestinal I/R-induced intestinal mucosal injury. 16,17 Therefore, the current study was undertaken to clarify whether propofol can prevent intestinal mucosa I/R injury, and to investigate its effects on NO, ET-1 release during intestinal I/R, in an in vivo rat model.…”

mentioning

confidence: 99%

Propofol attenuates intestinal mucosa injury induced by intestinal ischemia-reperfusion in the rat

Liu

Rinne

et al. 2007

Can J Anesth/J Can Anesth

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Purpose:We investigated whether propofol at a sedative dose can prevent intestinal mucosa ischemia/reperfusion (I/R) injury, and if propofol can attenuate oxidative stress and increases in nitric oxide (NO) and endothelin-1 (ET-1) release that may occur during intestinal I/R injury. Methods:Rats were randomly allocated into one of five groups (n = 10 each): (i) sham control; (ii) injury (one hour superior mesenteric artery occlusion followed by three hours reperfusion); (iii) propofol pre-treatment, with propofol given 30 min before inducing intestinal ischemia; (iv) simultaneous propofol treatment, with propofol given 30 min before intestinal reperfusion was started; (v) propofol post-treatment, with propofol given 30 min after intestinal reperfusion was initiated. In the treatment groups, propofol 50 mg·kg -1 was administrated intraperitoneally. Animals in the control and untreated injury groups received equal volumes of intralipid (the vehicle solution of propofol) intraperitoneally. Intestinal mucosa histology was analyzed by Chiu's scoring assessment. Levels of lactic acid (LD), NO, ET-1, lipid peroxidation product malondialdehyde (MDA) and superoxide dismutase (SOD) activity in intestinal mucosa were determined. Results:Histological results showed severe damage in the intestinal mucosa of the injury group accompanied by increases in MDA, NO and ET-1 and a decrease in SOD activity. Propofol treatments, especially pre-treatment, significantly reduced Chiu's scores and levels of MDA, NO, ET-1 and LD, while restoring SOD activity. Conclusion:These findings indicate that propofol attenuates intestinal I/R-induced mucosal injury in an animal model. The response may be attributable to propofol's antioxidant properties, and the effects of inhibiting over-production of NO and in decreasing ET-1 levels. CAN J ANESTH 2007 / 54: 5 / pp 366-374 Objectif : Nous avons cherché à savoir si le propofol, en dose sédative, pouvait empêcher les lésions d'ischémie/reperfusion (I/R) de la muqueuse intestinale, et s'il pouvait atténuer le stress oxydatif et les augmentations dans la libération d'oxyde nitrique (NO) et d'endothéline-1 (ET-1) pouvant survenir lors de lésions I/R intestinales. Méthode : Des rats ont été randomisés en cinq groupes (n = 10 chacun) : (i) faux témoin (sham control) ; (ii) lésion (occlusion de

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“…The continuous actions of these sequential events ultimately lead to necrotic cell death. Reperfusion during ischemia replenishes oxygen supply to the brain tissue, restoring energy and ionic homeostasis to a certain extent but this process actually exacerbates ischemic injury due to elevated production of oxygen-and nitrogen-derived free radicals (9,27). Free radicals confer considerable oxidative stress on the brain during reperfusion due to the high rate of oxidative metabolic activity, high levels of polyunstaturated fatty acids leading to lipid peroxidation and DNA damage (9,10).…”

Section: Inflammation In Strokementioning

confidence: 99%

Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists

Kapadia

Yi²,

Vemuganti³

2008

Front Biosci

374

246

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Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear hormone receptor superfamily. The 3 PPAR isoforms (alpha, delta/beta and gamma) are known to control many physiological functions including glucose absorption, lipid balance, and cell growth and differentiation. Of interest, PPAR-gamma activation was recently shown to mitigate the inflammation associated with chronic and acute neurological insults. Particular attention was paid to test the therapeutic potential of PPAR agonists in acute conditions like stroke, spinal cord injury (SCI) and traumatic brain injury (TBI), in which massive inflammation plays a detrimental role. While 15d-prostaglandin J2 (15d PGJ 2 ) is the natural ligand of PPAR-gamma, the thiazolidinediones (TZDs) are potent exogenous agonists. Due to their insulin-sensitizing properties, 2 TZDs rosiglitazone and pioglitazone are currently FDA-approved for type-2 diabetes treatment. Recent studies from our laboratory and other groups have shown that TZDs induce significant neuroprotection in animal models of focal ischemia and SCI by multiple mechanisms. The beneficial actions of TZDs were observed to be both PPAR-gamma-dependent as well as -independent. The major mechanism of TZD-induced neuroprotection seems to be prevention of microglial activation and inflammatory cytokine and chemokine expression. TZDs were also shown to prevent the activation of pro-inflammatory transcription factors at the same time promoting the anti-oxidant mechanisms in the injured CNS. This review article discusses the multiple mechanisms of TZDinduced neuroprotection in various animal models of CNS injury with an emphasis on stroke. KeywordsTranscription Factor; Inflammation; Brain Damage; Nuclear Factor; Cerebral Ischemia; Stroke; Neuroprotection; Review INTRODUCTIONStroke is the leading cause of long-term disability in the adult population worldwide. A variety of pathophysiological processes contribute to the irreversible neuronal injury that eventually results in neurological dysfunction after stroke. The complex nature of these processes involves specific cell types that effect several downstream signalling pathways. In a majority of stroke patients, only a small area of the brain tissue, the ischemic core, is irreversibly damaged. A much larger volume of the brain tissue surrounding the ischemic core, called the penumbra, can potentially recover if treatment is provided in a timely manner (3). Tissue protection and regeneration are tightly regulated by cell growth, survival and cell death signals provided by the cellular microenvironment. Hence, understanding the molecular mechanisms that govern Send correspondence to: Dr. Raghu Vemuganti, Department of Neurological Surgery, K4/8 Mail code CSC 8660, 600 Highland Avenue, Madison, WI 53792, Tel:608-263-4055, Fax:608-263-1728, E-mail: vemugant@neurosurg.wisc.edu. NIH Public Access Author ManuscriptFront Biosci. Author manuscript; available in PMC 2009 August 28. Published in final edited form as:Fr...

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Role of Induced Nitric Oxide in the Initiation of the Inflammatory Response After Postischemic Injury

Cited by 118 publications

References 28 publications

Biphasic Action of Inducible Nitric Oxide Synthase in a Hindlimb Ischemia Model

Biphasic Action of Inducible Nitric Oxide Synthase in a Hindlimb Ischemia Model

Propofol attenuates intestinal mucosa injury induced by intestinal ischemia-reperfusion in the rat

Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists

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