Nitrogen dioxide-induced acute lung injury in sheep

Januszkiewicz, Adolph J.; Mayorga, Maria

doi:10.1016/0300-483x(94)90101-5

Cited by 9 publications

(2 citation statements)

References 28 publications

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“…Such ciliary lesions appear to be reversible when NO 2 exposure is stopped (Ranga and Kleinerman, 1981). In addition to the mouse NO 2 injury lung models, rat (Meulenbelt et al, 1992a), rabbit (Meulenbelt et al, 1994) and sheep (Januszkiewicz and Mayorga, 1994) NO 2 injury lung models have also been described.…”

Section: In Vivo Injury Models Of the Lung Overviewmentioning

confidence: 99%

Stem Cells in the Lung

Liu

Driskell²,

Engelhardt³

2006

Methods in Enzymology

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The lung is composed of two major anatomically distinct regions-the conducting airways and gas-exchanging airspaces. From a cell biology standpoint, the conducting airways can be further divided into two major compartments, the tracheobronchial and bronchiolar airways, while the alveolar regions of the lung make up the gas-exchanging airspaces. Each of these regions consists of distinct epithelial cell types with unique cellular physiologies and stem cell compartments. This chapter focuses on model systems with which to study stem cells in the adult tracheobronchial airways, also referred to as the proximal airway of the lung. Important in such models is an appreciation for the diversity of stem cell niches in the conducting airways that provide localized environmental signals to both maintain and mobilize stem cells in the setting of airway injury and normal cellular turnover. Because cellular turnover in airways is relatively slow, methods for analysis of stem cells in vivo have required prior injury to the lung. In contrast, ex vivo and in vitro models for analysis of airway stem cells have used genetic markers to track lineage relationships together with reconstitution systems that mimic airway biology. Over the past decades, several widely acceptable methods have been developed and used in the characterization of adult airway stem/progenitor cells. These include localization of label-retaining cells (LRCs), retroviral tagging of epithelial cells seeded into xenografts, air-liquid interface cultures to track clonal proliferative potential, and multiple transgenic mouse models. This chapter reviews the biologic context and use of these models while providing detailed methods for several of the more broadly useful models for studying adult airway stem/progenitor cell types.

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Section: In Vivo Injury Models Of the Lung Overviewmentioning

confidence: 99%

Stem Cells in the Lung

Liu

Driskell²,

Engelhardt³

2006

Methods in Enzymology

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“…For example, it induces lung toxicity by the inhalation of air containing 50-100 ppm of the gas. 35 Enhancement of its endogenous generation by the induction of NO synthases has also been shown to be involved in many aging manifestations, such as Alzheimer's disease, cardiac myopathies, erectile dysfunction, hormone replacement therapy in elderly women, senile macular degeneration, diabetic retinopathy, glaucoma, and uveitis. [36][37][38] Many of these conditions are associated with cataract formation.…”

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confidence: 99%

Susceptibility of the Ocular Lens to Nitric Oxide: Implications in Cataractogenesis

Varma

Hegde

2007

Journal of Ocular Pharmacology and Therapeutics

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Oxides of nitrogen, such as nitric oxide (NO), are now biologically referred to as reactive nitrogen species. The generation of NO gives rise to several other reactive species, such as NO+, NO-, NO2, N2O3, and ONOO- and so forth, which are all capable of inflicting tissue damage. Indeed, NO generation is known to be associated with retinal degeneration and glaucoma. Its level has also been found to increase in the aqueous and vitreous humors in diabetes. We hypothesize that such an increase would have a detrimental effect on the biochemistry and metabolism of tissues, including the lens, bathed by the aqueous containing elevated levels of NO. The primary aim of our investigations was, therefore, to examine the susceptibility of the lens to damage by NO in vitro in the presence of nitroaspirin, a novel NO donating agent. The extent of physiologic damage to the lens was initially assessed by determining the integrity of its active transport mechanism. The overall status of tissue metabolism was determined by measuring the adenosine triphosphate (ATP) levels. The levels of glutathione (GSH) and glutathione disulfide, reflecting the status of its antioxidant reserve, were also determined. That NO is indeed deleterious to the lens was apparent by the inhibition of the active transport of Rb(+). This was associated with a substantial decrease in the contents of ATP and GSH, the decrease in the latter directly suggesting that the NO effects are caused by oxidative stress. That the effects are caused by NO generated from nitroaspirin was proven by a substantial increase in NO level in the medium during incubation of the lenses with nitroaspirin, as compared to the controls. The results, therefore, were highly suggestive of a contribution of the oxides of nitrogen in cataract formation associated with diabetes and other aging diseases.

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Medicinal Chemistry and Therapeutic Applications of the GasotransmittersNO,CO, andH₂Sand their Prodrugs

Szabó

2010

Burger's Medicinal Chemistry and Drug Discovery

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Nitric oxide ( NO ), carbon monoxide ( CO ), and hydrogen sulfide ( H 2 S ) are the main endogenous gasotransmitters. These gases are produced by the body by enzymatic reactions and serve physiological regulatory purposes including vasodilatation and anti‐inflammatory effects. Over the past decades, multiple approaches have been identified for the therapeutic exploitation of these three gasotransmitters, based on inhalation of the gases and/or the parenteral or enteral administration of various formulations of these molecules or their prodrugs. Here we overview the medicinal chemistry and the therapeutic applications of NO, CO, and H 2 S and their prodrugs. Inhaled NO is used clinically to selectively dilate the pulmonary vasculature in the therapy of the primary pulmonary hypertension of the newborn. Organic nitrates such as glyceryl trinitrate or nitroglycerin are used in the therapy of acute and chronic angina. Sodium nitroprusside is used to counteract acute hypertensive crisis. Another class of clinical‐stage NO donor drugs is the sydnonimines (molsidomine, linsidomine). Additional classes of NO donors include diazeniumdiolates (NONOates) and S ‐nitrosothiols, with beneficial effects in various preclinical models of disease. With respect to CO, the main therapeutic approaches are CO inhalation (currently in clinical trials for the experimental therapy of delayed graft function associated with kidney transplantation) and carbon monoxide releasing compounds of various classes (in preclinical stage). With respect to H 2 S, a parenteral injectable formulation of the gas is currently is Phase I trials. Several classes of H 2 S donor molecules have also been identified, which are used in preclinical studies.

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Nitrogen dioxide-induced acute lung injury in sheep

Cited by 9 publications

References 28 publications

Stem Cells in the Lung

Stem Cells in the Lung

Susceptibility of the Ocular Lens to Nitric Oxide: Implications in Cataractogenesis

Medicinal Chemistry and Therapeutic Applications of the GasotransmittersNO,CO, andH₂Sand their Prodrugs

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Nitrogen dioxide-induced acute lung injury in sheep

Cited by 9 publications

References 28 publications

Stem Cells in the Lung

Stem Cells in the Lung

Susceptibility of the Ocular Lens to Nitric Oxide: Implications in Cataractogenesis

Medicinal Chemistry and Therapeutic Applications of the GasotransmittersNO,CO, andH2Sand their Prodrugs

Contact Info

Product

Resources

About

Medicinal Chemistry and Therapeutic Applications of the GasotransmittersNO,CO, andH₂Sand their Prodrugs