The Chemistry of Nitroxyl-Releasing Compounds

DuMond, Jenna F.; King, S. Bruce

doi:10.1089/ars.2010.3838

Cited by 85 publications

(84 citation statements)

References 95 publications

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“…However, NO is a very unstable free radical and that is why its delivery needs another molecule to which NO would be attached to reach the liver. Some of the potential NO donors that could be used are S-nitrosothiols, diazeniumdiolates and liver-selective NO donors (72)(73)(74)(75)(76). All these molecules have been tested in numerous studies, with the S-nitrosothiols being the most studied of all.…”

Section: Nitric Oxidementioning

confidence: 99%

Hepatic Ischemia and Reperfusion Injury and Trauma: Current Concepts

Papadopoulos¹,

Siempis²,

Theodorakou³

et al. 2013

Arch Trauma Res

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Context: Ischemia-reperfusion injury is a fascinating topic which has drawn a lot of interest in the last several years. Hepatic ischemia reperfusion injury may occur in a variety of clinical situations. These include transplantation, liver resection, trauma, and vascular surgery. Evidence Acquisition: The purpose of this review was to outline the molecular mechanisms underlying hepatic I/R injury and present the latest approaches, both surgical and pharmacological, regarding the prevention of it. A comprehensive electronic literature search in MEDLINE/PubMed was performed to identify relative articles published within the last 2 years. Results: The basic mechanism of hepatic ischemia -reperfusion injury is one of blood deprivation during ischemia, followed by the return of flow during reperfusion. It involves a complex series of events, such as mitochondrial deenergization, adenosine-5'-triphosphate depletion, alterations of electrolyte homeostasis, as well as Kupffer cell activation, oxidative stress changes and upregulation of proinflammatory cytokine signaling. The great number of variable pathways, with several mediators interacting with each other, leads to a high number of candidates for potential therapeutic intervention. As far as surgical approaches are concerned, the modification of existing clamping techniques and the ischemic preconditioning are the most promising techniques till recently. In the search for novel techniques of protecting against hepatic ischemia reperfusion injury, many different strategies have been used in experimental models. The biggest part of this research lies around antioxidant therapy, but other potential solutions have been explored as well. Conclusions:The management of hepatic trauma, in spite of the fact that it has become increasingly nonoperative, there still remains the possibility of hepatic resection in the hepatic trauma setting, especially in severe injuries. Hence, clinicians should be familiar with the concept of hepatic ischemia-reperfusion injury and respond appropriately and timely.Keywords: Reperfusion Injury; Ischemia; Pathophysiology; Prevention Implication for health policy/practice/research/medical education: Hepatic ischemia and reperfusion injury is a complex phenomenon which is commonplace in clinical practice such as the operative management of hepatic trauma, liver transplantation and liver resection. Hence, surgeons should be familiar with it and apply the necessary methods to prevent it.

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Section: Nitric Oxidementioning

confidence: 99%

Hepatic Ischemia and Reperfusion Injury and Trauma: Current Concepts

Papadopoulos¹,

Siempis²,

Theodorakou³

et al. 2013

Arch Trauma Res

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“…Comprehensive reviews of HNOreleasing compounds are already available [20][21][22][23][24], so here some of the spontaneous donors are only briefly mentioned. One of the most widely used HNO releasers is Angeli's salt (Na 2 N 2 O 3 , 1) [25,26], which decomposes under physiological conditions, producing HNO concomitantly with nitrite.…”

Section: Hno Donors That Exhibit Spontaneous Releasementioning

confidence: 99%

Controlled release of HNO from chemical donors for biological applications

Nakagawa

2013

Journal of Inorganic Biochemistry

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“…Furthermore, prior HNO studies have mostly employed Angeli's salt (AS) that degrades into HNO but also nitrite which is itself a vasodilator 34 . Some have used IPA/NO, which is a pH dependent HNO donor 35 , while others acyloxy-nitroso compounds that are limited to in vitro use 36, 37 . Here, we performed studies in mice genetically lacking the sGCβ1 subunit 38 that results in loss of the entire sGC protein complex.…”

Section: Introductionmentioning

confidence: 99%

Soluble Guanylate Cyclase Is Required for Systemic Vasodilation But Not Positive Inotropy Induced by Nitroxyl in the Mouse

et al. 2015

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Nitroxyl (HNO), the reduced and protonated form of nitric oxide (NO.), confers unique physiological effects including vasorelaxation and enhanced cardiac contractility. These features have spawned current pharmaceutical development of HNO donors as heart failure therapeutics. HNO interacts with selective redox sensitive cysteines to effect signaling, but is also proposed to activate soluble guanylate cyclase (sGC) in vitro to induce vasodilation and potentially enhance contractility. Here we tested whether sGC stimulation is required for these HNO effects in vivo and if HNO also modifies a redox-sensitive cysteine (C42) in protein kinase G-1α (PKG1α) to control vasorelaxation. Intact mice and isolated arteries lacking the sGC-β subunit (sGCKO, results in full sGC deficiency) or expressing solely a redox-dead C42S mutant PKG1α were exposed to the pure HNO donor, CXL-1020. CXL-1020 induced dose-dependent systemic vasodilation while increasing contractility in controls; however, vasodilator effects were absent in sGCKO mice whereas contractility response remained. The CXL-1020 dose reversing 50% of pre-constricted force in aortic rings was ~400-fold greater in sGCKO than controls. Cyclic-GMP and cAMP levels were unaltered in myocardium exposed to CXL-1020 despite its inotropicvasodilator activity. In PKG1αC42S mice, CXL-1020 induced identical vasorelaxation in vivo and in isolated aortic and mesenteric vessels as in littermate controls. In both groups, dilation was near fully blocked by pharmacologically inhibiting sGC. Thus, sGC and cGMP-dependent signaling are necessary and sufficient for HNO-induced vasodilation in vivo, but are not required for positive inotropic action. Redox modulation of PKG1α is not a mechanism for HNO-mediated vasodilation.

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The Chemistry of Nitroxyl-Releasing Compounds

Cited by 85 publications

References 95 publications

Hepatic Ischemia and Reperfusion Injury and Trauma: Current Concepts

Hepatic Ischemia and Reperfusion Injury and Trauma: Current Concepts

Controlled release of HNO from chemical donors for biological applications

Soluble Guanylate Cyclase Is Required for Systemic Vasodilation But Not Positive Inotropy Induced by Nitroxyl in the Mouse

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