Cholesterol ozonation products as biomarkers for ozone exposure in rats

Pryor, William A.; Wang, Keyang; Bermúdez, Eliezer

doi:10.1016/0006-291x(92)91101-u

Cited by 48 publications

(40 citation statements)

References 11 publications

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“…The easy accessability of cutaneous tissues for bioassay purposes suggests that the stratum corneum could serve as a dosimeter for assessing environmental oxidative damage such as that caused by 03. Such biomarkers have already been described for the case of 03 reactions at respiratory tract surfaces (117). A review of biomarkers of oxidative damage to lipids, proteins, and DNA has recently been published (118).…”

Section: Barrier Antioxidants Of Skinmentioning

confidence: 99%

Oxidative stress and antioxidants at biosurfaces: plants, skin, and respiratory tract surfaces.

Cross

Vliet

Louie

et al. 1998

Environ Health Perspect

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Atmospheric pollutants represent an important source of oxidative and nitrosative stress to both terrestrial plants and to animals. The exposed biosurfaces of plants and animals are directly exposed to these pollutant stresses. Not surprisingly, living organisms have developed complex integrated extracellular and intracellular defense systems against stresses related to reactive oxygen and nitrogen species (ROS, RNS), including 03 and NO2. Plant and animal epithelial surfaces and respiratory tract surfaces contain antioxidants that would be expected to provide defense against environmental stress caused by ambient ROS and RNS, thus ameliorating their injurious effects on more delicate underlying cellular constituents. Parallelisms among these surfaces with regard to their antioxidant constituents and environmental oxidants are presented. The reactive substances at these biosurfaces not only represent an important protective system against oxidizing environments, but products of their reactions with ROS/RNS may also serve as biomarkers of environmental oxidative stress. Moreover, the reaction products may also induce injury to underlying cells or cause cell activation, resulting in production of proinflammatory substances including cytokines. In this review we discuss antioxidant defense systems against environmental toxins in plant cell wall/apoplastic fluids, dead keratinized cells/interstitial fluids of stratum corneum (the outermost skin layer), and mucus/respiratory tract lining fluids.-Environ Health Perspect 1 06(Suppl 5): 1241-1251 (1998 The aim of this review is to highlight certain parallels between the antioxidant mechanisms responsible for protecting diverse environmentally exposed biosurfaces. Although there are numerous other environmental oxidants that contribute to surface oxidative stress (e.g., oxides of nitrogen, cigarette smoke, radiation), our focus will be on 03 as a representative environmental oxidant and on the antioxidants with which it can be expected to react at plant, skin, and respiratory tract surfaces. Although in most circumstances the oxidant can be expected to be neutralized, products of reactions with constituents of the extracellular fluids, e.g., cytotoxic aldehydes produced by reactions of 03 with extracellular lipids (12-14), may be largely responsible for cell or tissue injury by environmental toxins. Structural ConsiderationsThe similarities of the interfaces between the environment and plant and animal tissues are simplistically depicted in Figure 1. In plants, uptake of environmental toxins can be expected to occur mainly at the cell wall surface and, via the stomata, within the extracellular apoplastic fluids (15-17). The skin and the respiratory tract are the animal organs most direcdy exposed to oxidant air pollutants. Although numerous studies have documented the effects of oxidants on lungs, and have to some extent directed attention to the importance of the respiratory tract lining fluids (RTLFs) (18)(19)(20)(21)(22), only a few studies have described possible oxi...

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Section: Barrier Antioxidants Of Skinmentioning

confidence: 99%

Oxidative stress and antioxidants at biosurfaces: plants, skin, and respiratory tract surfaces.

Cross

Vliet

Louie

et al. 1998

Environ Health Perspect

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“…Reduction of 5-hydroperoxy-B-homo-6-oxacholestane-3␤,7a-diol has been shown to primarily yield 3␤-hydroxy-5-oxo-5,6-secocholestan-6-al (5,6-seco-sterol) (11)(12)(13). In fact, this reduced product has been detected in lung homogenate and broncheoalveolar lavage fluid of rats exposed to ozone, and it has thus been suggested as a biomarker for ozone exposure (16). The recent observation of 5,6-seco-sterol in arterial plaques has provided evidence that the formation of ozone may also occur as the result of normal biochemical events taking place in vivo during an inflammatory response (17).…”

mentioning

confidence: 99%

Formation of Biologically Active Oxysterols during Ozonolysis of Cholesterol Present in Lung Surfactant

Pulfer

Murphy

2004

Journal of Biological Chemistry

105

102

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Exposure of the lung to concentrations of ozone found in ambient air is known to cause toxicity to the epithelial cells of the lung. Because of the chemical reactivity of ozone, it likely reacts with target molecules in pulmonary surfactant, a lipid-rich material that lines the epithelial cells in the airways. Phospholipids containing unsaturated fatty acyl groups and cholesterol would be susceptible to attack by ozone, which may lead to the formation of cytotoxic products. Whereas free radicalderived oxidized cholesterol products have been frequently studied for their cytotoxic effects, ozonized cholesterol products have not been studied, although they could reasonably play a role in the toxicity of ozone. The reaction of ozone with cholesterol yielded a complex series of products including 3␤-hydroxy-5-oxo-5,6-secocholestan-6-al, 5-hydroperoxy-B-homo-6-oxa-cholestan-3␤,7a-diol, and 5␤,6␤-epoxycholesterol. Mass spectrometry and radioactive monitoring were used to identify the major cholesterol-derived product during the reaction of 2 ppm ozone in surfactant as 5␤,6␤-epoxycholesterol, which is only a minor product during ozonolysis of cholesterol in solution. A dose-dependent formation of 5␤,6␤-epoxycholesterol was also seen during direct exposure of intact cultured human bronchial epithelial cells (16-HBE) to ozone. Studies of the metabolism of this epoxide in lung epithelial cells yielded small amounts of the expected metabolite, cholestan-3␤,5␣,6␤-triol, and more abundant levels of an unexpected metabolite, cholestan-6-oxo-3␤,5␣-diol. Both 5␤,6␤-epoxycholesterol and cholestan-6-oxo-3␤,5␣-diol were shown to be cytotoxic to cultured 16-HBE cells. A possible mechanism for cytotoxicity is the ability of these oxysterols to inhibit isoprenoid-based cholesterol biosynthesis in these cells.Human exposure to 0.2 ppm levels of ozone in ambient air has been shown to cause numerous pulmonary effects such as increased airway inflammation and decreased pulmonary function (1, 2). Studies of ozone in animals using up to 3 ppm ozone have been shown to cause increased airway hyperresponsiveness and epithelial cell death. It has been hypothesized that the very high chemical reactivity of ozone limits the distribution of this gas in the pulmonary system, preventing direct exposure to the cellular components of the lung. In part ozone may react with the various components of the epithelial cell lining fluid in the lung, also known as pulmonary surfactant, which includes proteins, lipids, and single electron antioxidant agents such as ascorbic acid (3-5). Because of the very high reactivity of ozone with lipids containing double bonds, considerable emphasis has been placed on the reaction of ozone with lipid compounds in the lungs and the possibility that the adverse effects of ozone are mediated by lipid-ozonized products (6). Evidence in support of this theory has been accumulating with the identification of biologically active phospholipids (7) such as 1-hexadecanoyl-2-(9-oxo-nonanoyl)-glycerophosphocholine, found following oz...

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“…Previous studies have determined the impact that ozonization of lipids, particularly polyunsaturated fatty acids (PUFA), may have on O 3 -associated toxic effects. These studies demonstrated that ozonization of PUFAs and the formation of lipid ozonization products can mimic many of the adverse health effects observed after exposure to O 3 (5,(7)(8)(9). However, the involvement of cholesterol ozonization products requires further study.…”

mentioning

confidence: 99%

“…As a very potent oxidant gas, O 3 reacts readily with the surface components of the airway and causes cellular modification through reactions with the airwaylining fluid and epithelial cellular membranes (2)(3)(4). The lunglining fluid and epithelial cell membranes are rich in cholesterol and other lipids, which can be directly oxidized by O 3 (5,6). Previous studies have determined the impact that ozonization of lipids, particularly polyunsaturated fatty acids (PUFA), may have on O 3 -associated toxic effects.…”

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confidence: 99%