Nutrition and lung health.

Several lung diseases have been associated with oxidative stress and linked to oxidant insults such as cigarette smoke, air pollutants and infections. Consequently, dietary factors and nutrients with a potential protective role in the oxidative process and inflammatory response have been implicated in the genesis or evolution of these diseases. These nutrients include fruits and vegetables, antioxidant vitamins such as vitamin C, vitamin E, betacarotene and other carotenoids, vitamin A, fatty acids and some minerals such as sodium, magnesium and selenium. This article reviews the potential mechanisms by which dietary factors may affect respiratory health, and discusses epidemiological evidence for the link between diet and lung diseases. Most of the available evidence on the effect of dietary factors on the risk for obstructive lung diseases are derived from cross-sectional studies. These studies suggest that antioxidant vitamins, particularly vitamin C, and to a lesser extent other antioxidants, have a protective effect against lung diseases. However, the few intervention studies have not been conclusive. High intake of fresh fruit and some vegetables appears to have a beneficial effect on lung health and their consumption should be recommended on a daily basis. Supplementation of vitamin C and other antioxidants could be proposed in subjects with additional oxidative stress challenge, such as exposure to high levels of air pollution. Subjects with impaired immune response could also benefit from vitamin A and zinc supplementation. Further studies are needed to determine the impact of diet on the incidence and evolution of lung diseases.     

Effects of dietary selenium and vitamin E on plasma lipoprotein cholesterol levels in male rats

Male Fischer-344 rats fed a diet deficient in both vitamin E and selenium (Se) for 20 weeks had higher levels of low-density lipoprotein cholesterol than age-matched rats fed an identical diet but supplemented with these micronutrients. The rats supplemented with both vitamin E and Se were switched to a diet deficient in both these micronutrients at week 20. These rats eventually developed elevated levels of low-density lipoprotein cholesterol compared to age-matched rats either continuously maintained on the diet supplemented with vitamin E and Se or rats switched (at week 20) from the vitamin E-and Se-deficient diet to a diet supplemented with both these micronutrients. In a second experiment, we found that Se deficiency alone was sufficient to significantly elevate low-density lipoprotein cholesterol. The basal diet used in these experiments had a very low cholesterol content and the observed alterations in lipoprotein cholesterol levels are likely to reflect alterations in the metabolism of endogenously synthesized cholesterol.     

Antioxidant diet protects against emphysema, but increases mortality in cigarette smoke-exposed mice

Oxidative stress plays an important role in cigarette smoke-induced lung inflammation and emphysema. We produced an enriched diet by adding freeze-dried fruits and vegetables and additional supplements to the 8604 Teklad Rodent Diet, a standard rodent diet. In this study, we examined the effects of the antioxidant-enriched diet on cigarette smoke-induced lung inflammation and emphysema. CH3/HeN mice were fed either a regular diet or the supplemented diet. These mice were exposed to filtered air, a low concentration of cigarette smoke (total particulate matter: 100 mg/m3) or a high concentration of cigarette smoke (total particulate matter: 250 mg/m3) for 6 h/day, 5 days/week for total 16 weeks. Surprisingly, increased mortality (53%) was observed in the high concentration of cigarette smoke-exposed mice fed the antioxidant diet compared to the high concentration of cigarette smoke-exposed mice that were fed a regular diet (13%). The necropsy analysis revealed nasal passage obstruction due to mucous plugging in cigarette smoke-exposed mice on the antioxidant diet. However, the antioxidant diet significantly reduced neutrophilic inflammation and emphysema in the high concentration of cigarette smoke-exposed mice as compared to the regular diet /high concentration of cigarette smoke controls. The antioxidant capacity in the bronchoalveolar fluid or oxidative damage to the lung tissue was not affected by the antioxidant diet. Pro-MMP-2, MMP-2, and MMP-9 activity did not correlate with the protective effects of AOD on cigarette smoke-induced emphysema. These data suggest that the antioxidant diet reduced cigarette smoke-induced inflammation and emphysema, but increased mortality in the obligate nose-breathing mice.     

Antioxidant Diet Protects Against Emphysema,but Increases Mortality in Cigarette Smoke-Exposed Mice

Oxidative stress plays an important role in cigarette smoke-induced lung inflammation and emphysema. We produced an enriched diet by adding freeze-dried fruits and vegetables and additional supplements to the 8604 Teklad Rodent Diet, a standard rodent diet. In this study, we examined the effects of the antioxidant-enriched diet on cigarette smoke-induced lung inflammation and emphysema. CH3/HeN mice were fed either a regular diet or the supplemented diet. These mice were exposed to filtered air, a low concentration of cigarette smoke (total particulate matter: 100 mg/m³) or a high concentration of cigarette smoke (total particulate matter: 250 mg/m³) for 6 h/day, 5 days/week for total 16 weeks. Surprisingly, increased mortality (53%) was observed in the high concentration of cigarette smoke-exposed mice fed the antioxidant diet compared to the high concentration of cigarette smoke-exposed mice that were fed a regular diet (13%). The necropsy analysis revealed nasal passage obstruction due to mucous plugging in cigarette smoke-exposed mice on the antioxidant diet. However, the antioxidant diet significantly reduced neutrophilic inflammation and emphysema in the high concentration of cigarette smoke-exposed mice as compared to the regular diet /high concentration of cigarette smoke controls. The antioxidant capacity in the bronchoalveolar fluid or oxidative damage to the lung tissue was not affected by the antioxidant diet. Pro-MMP-2, MMP-2, and MMP-9 activity did not correlate with the protective effects of AOD on cigarette smoke-induced emphysema. These data suggest that the antioxidant diet reduced cigarette smoke-induced inflammation and emphysema, but increased mortality in the obligate nose-breathing mice.     

Oxidants in cigarette smoke extract modify low-density lipoprotein in the plasma and facilitate atherogenesis in the aorta of Watanabe heritable hyperlipidemic rabbits

Epidemiological studies have shown that cigarette smoking is a major cause of atherosclerosis. Oxidants as well as nicotine in cigarette smoke have been implicated in atherogenesis. To clarify the mechanism involved, we examined the chronic effects of nicotine and nicotine-free cigarette smoke extracts (CSE) on oxidative modification of low-density lipoprotein (LDL) in the plasma of Watanabe heritable hyperlipidemic rabbits and atherogenesis in the aorta. CSE was prepared by bubbling the gas phase of smoke (1 ml/three cigarettes) into phosphate buffer saline, and 3 ml of this CSE was injected daily into the ear vein of the rabbit for five months. The rabbits treated with CSE showed an increase in lipid peroxide levels, estimated as thiobarbituric acid reactive substances (TBARS), with a corresponding decrease in vitamin E levels in the plasma. They also showed enhanced oxidative modification of LDL, assessed by anion-exchange HPLC, incorporation into macrophages and measurement of TBARS. These events could be efficiently prevented by administering vitamin E (150 mg/kg/day, p.o.). Nicotine alone (0.5 mg/kg/day, s.c.) led to a temporary increase in the plasma triglyceride level. At the end of the experiment, CSE but not nicotine had caused progression of atherosclerotic lesions together with accumulation of cholesteryl ester in the thoracic aorta, while vitamin E had significantly prevented such atheromatous formation. These results indicate that oxidants in CSE can promote the development of atherosclerosis through oxidative modification of plasma LDL, particularly in hypercholesterolemia, and offer evidence for increased vitamin E utilization in smokers.     

Relationship of serum antioxidants to asthma prevalence in youth

The relationship of serum vitamin E, beta-carotene, vitamin C, and selenium to asthma was investigated among 7,505 youth (4-16 years old) in the Third National Health and Nutrition Examination Survey. Logistic regression models adjusted for potentially confounding variables, which generally had no effect on the coefficients for the antioxidants. Serum vitamin E had little or no association with asthma. In separate models, a SD increase in beta-carotene (odds ratio [OR], 0.9; 95% confidence interval [CI], 0.7, 1.0), vitamin C (OR, 0.8; 95% CI, 0.7, 0.9), and selenium (OR, 0.9; 95% CI, 0.7, 1.1) was associated with a 10-20% reduction in asthma prevalence. Serum cotinine was used to identify youth with no cigarette smoke exposure and passive exposure (7%): Active smokers were too few to be studied further. The selenium-asthma association was stronger in youth who were smoke exposed (p = 0.075). A SD increase in selenium was associated with a 50% reduction in asthma prevalence (OR, 0.5; 95% CI, 0.2, 1.4) in youth with passive smoke exposure compared with a 10% reduction in youth with no smoke exposure. The findings support an association of antioxidants with prevalent asthma, which for some antioxidants is stronger among children exposed to cigarette smoke.     

硒和维生素E对大鼠心肌单胺类物质和单胺氧化酶的影响

本文观察了硒（Ｓｅ）和维生素Ｅ（ＶＥ）对大鼠心肌去甲肾上腺素（ＮＥ）、多巴胺（ＤＡ）、５羟色胺（５－ＨＴ）含量和单胺氧化酶Ａ（ＭＡＯ－Ａ）、单胺氧化酶Ｂ（ＭＡＯ－Ｂ）活性的影响，发现经低Ｓｅ、低ＶＥ饲料喂养１０周，并且处死前经２次冰浴刺激的大鼠心肌ＮＥ含量明显增高，ＭＡＯ－Ａ活性降低，ＭＡＯ－Ｂ活性增加，通过补充饲料中Ｓｅ和ＶＥ，对上述指标有不同程度的改善，并以联合补充Ｓｅ和ＶＥ效果最佳。本研究结     

Probucol and antioxidant vitamins rescue ischemia-induced neovascularization in mice exposed to cigarette smoke: Potential role of endothelial progenitor cells

ObjectiveCigarette smoking is associated with impaired neovascularization in response to ischemia. Potential mechanisms include increased generation of reactive oxygen species (ROS) and a reduction in the function of endothelial progenitor cells (EPCs). Here we tested the hypothesis that antioxidant therapies could stimulate EPC function and improve ischemia-induced neovascularization following cigarette smoke exposure.Methods and resultsC57Bl/6 mice exposed to cigarette smoke (MES) were fed a normal diet (controls) or a diet supplemented with probucol (0.5%) or a combination of vitamin C (25 g/l in drinking water) and vitamin E (0.1% in normal chow). After two weeks of treatment, hindlimb ischemia was surgically induced by femoral artery removal. Exposure to cigarette smoke was associated with a significant reduction of blood flow recuperation and vessel density in ischemic muscles. However, a complete rescue of neovascularization was demonstrated in MES treated with probucol or antioxidant vitamins. We found that antioxidant therapy in MES is associated with a significant reduction of oxidative stress levels both in the plasma and in ischemic muscles. Moreover, EPCs exposed to cigarette smoke extracts in vitro showed a significant impairment of their angiogenic activities (migration, adhesion, homing into ischemic tissues) that was completely rescued by probucol and antioxidant vitamins.ConclusionsProbucol and antioxidant vitamins rescue cigarette smoke-dependent impairment of ischemia-induced neovascularization. The mechanisms involve beneficial effects on oxidative stress levels in ischemic tissues together with an improvement of EPC functional activities. Antioxidant therapy could constitute a novel therapeutic strategy to promote vessel growth and reduce tissue ischemia in atherosclerotic diseases.     

Effect of dietary selenium and vitamin E on the biomechanical properties of rabbit bones

Summary It is generally agreed that combined deficiency of selenium and vitamin E leads to several abnormalities including Kashin-Beck disease which is an endemic and chronic degenerative osteoarthrosis. The abnormalities can be reversed by the administration of various forms of selenium and vitamin E.The present study was designed to investigate the effects of dietary selenium and vitamin E on bone tissue and on the biomechanical properties of bone. Young rabbits of both sexes were fed with either a selenium- and vitamin E-adequate diet (control group), or a selenium- and vitamin E-deficient diet or a selenium-excess diet. The selenium-deficient diet resulted in a significant decrease in plasma selenium level and the selenium-excess diet resulted in a significant increase in the plasma selenium level with respect to the corresponding control values (p<0.05). The diets did not affect the blood cell counts considerably but erythrocyte glutathione peroxidase activity increased (decreased) relatively when the plasma selenium level increased (decreased) (p<0.05). The light microscopic investigations of the bone tissues of the two experimental groups indicate that the findings of the present work are compatible with osteomalacia. The biomechanical properties of the bones from the three groups were determined experimentally with bending tests. Both the Se-and vitamin E-deficient diet and the Se-excess diet decreased the biomechanical strength of the bones significantly while the bones belonging to the control group always had the largest modulus of elasticity (p<0.05).     

氧化应激在慢性阻塞性肺疾病发生中的作用及防治策略

COPD 特征是慢性气道炎症、细小支气管重塑及肺实质破坏。研究表明,香烟烟雾等有害气体所引起的氧化应激在 COPD 发展过程起到了至关重要的作用。吸烟增强氧化应激,使氧化/抗氧化比例失衡,直接损伤肺组织,加重气道炎症反应,引起自身免疫反应,最终导致气流受限。因此,对抗氧化应激、提高宿主抗氧化能力,是 COPD 防治的最新着重点。     

亚硝酸钠对心肌谷胱甘肽过氧化物酶的影响及维生素E和硒的保护作用

大白鼠喂饲克山病病区粮,并分别向病区粮加维生素 E 和硒,观察在亚硝酸钠急性中毒情况下各组大鼠心肌谷胱甘肽过氧化物酶的变化。结果表明,亚硝酸钠可使病区粮所饲大鼠心肌谷胱甘肽过氧化物酶活性明显下降,补充维生素 E 或硒则可保护此酶活性防止其下降。提出除低硒外,亚硝酸盐过多及维生素 E 缺乏可能参与了克山病发病环节。     

Acute pulmonary injury in rats by nitrofurantoin and modification by vitamin E, dietary fat, and oxygen.

The subcutaneous administration of nitrofurantoin to rats caused severe pulmonary damage, characterized by edema, congestion, and hemorrhage. The acute lethality of the drug was greater in rats fed vitamin E-deficient diets high in polyunsaturated fats as compared to rats fed the NIH open-formula diet. The survival times of vitamin E-deficient rats were increased if such animals were fed diets supplemented with vitamin E and/or diets containing saturated fat (lard) for 3 weeks before administration of nitrofurantoin. The toxicity of nitrofurantoin was enhanced in both the rats deficient in vitamin E and in those given vitamin E supplements and exposed to O2-enriched atmospheres. These results, in conjunction with previous metabolic studies in vitro showing redox cycling and O2 activation in rat lung microsomes in the presence of nitrofurantoin, illustrate certain similarities with the lung-toxic herbicide, paraquat, and raise the question of whether the 2 agents may be capable of damaging lungs by a common mechanism.     

Preferential recruitment of neutrophils by endothelin-1 in acute lung inflammation induced by lipopolysaccharide or cigarette smoke

This study examined the role of endothelin-1 (ET-1) in recruiting inflammatory cells to the lung after induction of injury with either lipopolysaccharide (LPS) or cigarette smoke. Hamsters injected with either ET-1 or its precursor peptide (Big ET-1) prior to treatment with LPS or cigarette smoke had markedly increased concentrations of neutrophils in bronchoalveolar lavage fluid (BALF) despite a reduction in total numbers of BALF leukocytes. Furthermore, the effect of ET-1 on smoke-exposed animals was reversed by addition of an endothelin-A receptor antagonist. These results are consistent with preferential recruitment of neutrophils by ET-1, and suggest that inhibition of this proinflammatory mediator may decrease acute pulmonary inflammation associated with cigarette smoke and other pulmonary toxins.     

The effects of physical exercise on the cigarette smoke-induced pulmonary oxidative response

Studies have shown that the oxidative power of cigarettes is related to the pathogenesis of several pulmonary diseases and that regular physical exercise contributes significantly to reducing the deleterious effects of cigarettes. The objective of the present study was to investigate the therapeutic effects of physical exercise on histological and oxidative stress markers in animals exposed to cigarette smoke. Thirty-six male, eight-week-old C57BL-6 mice were divided into four groups (n = 9 for each group): control, exercise, cigarette smoke, and cigarette smoke plus exercise. The cigarette smoke (CS) groups were exposed to cigarette smoke 3 times/day (4 cigarettes/session) for 60 consecutive days. The exercise groups were submitted to swimming physical training 5 days/week for eight weeks. Forty-eight hours after the last exercise and cigarette exposure, the animals were sacrificed using cervical traction. The right lung was removed, processed, and stored for future analysis. In addition to the analysis of collagen content (hydroxyproline), oxidant production (anion superoxide), antioxidant enzyme activity (SOD and CAT), and lipid and protein oxidative damage (TBARS and Carbonylation), histological and morphological studies were performed. The results revealed that the animals exposed to cigarette smoke showed enlargement and destruction of the alveolar septum and increases in the numbers of macrophages and neutrophils, as well as in the amount of collagen. Our results also showed a decrease in the volume density of elastic fibers and an increase in the volume density of airspaces. However, physical exercise partially improved these markers. Additionally, physical exercise decreased oxidant production and increased the activity of the enzymatic antioxidant defense system, but did not reverse lipid and protein oxidative damage induced by cigarette smoke. These results suggest that physical training partially improves histological and oxidative stress parameters in the lungs of animals chronically exposed to cigarette smoke and that other therapies can contribute to potentiate these effects.     

低硒环境下蛋氨酸对大鼠体内维生素E,硒及脂质过氧化物含量的影响

用低硒、低蛋氨酸饲料喂养大鼠8周后发现大鼠血清、肝脏及心肌中脂质过氧化物含量显著升高,血清维生素E显著下降,而心肌硒含量却显著升高。实验结果表明,在低硒环境下如降低饲料中蛋氨酸水平将导致大鼠体内脂质过氧化反应加剧。     

The facilitating effect of cigarette smoke on the colonization of instilled bacteria into the tracheal lumen in rats and the improving influence of supplementary vitamin E on this process

OBJECTIVE: The aim of the present study was to investigate the direct influence of cigarette smoke on the bacterial colonization of the lower respiratory tract and the effect of supplementary vitamin E on the colonization of instilled bacteria into the trachea of rats that do not have the chronic airway pathology associated with smoking. METHODOLOGY: Thirty male Wistar albino rats, weighing approximately 250 g, were used as experimental animals. A 0.1 mL bacterial suspension containing six bacterial species (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumonia, Proteus mirabilis, Haemophilus influenza, Peptostreptococci spp.), isolated previously from pharynx of rats, were instilled into the trachea of three groups of rat (10 control, 10 cigarette smoke-treated and 10 cigarette smoke- and vitamin E-supplemented rats). The smoke-treated rats were exposed to cigarette smoke for 3 days prior to and after intratracheal instillation. The third group of rats were given vitamin E supplements (100 mg/kg per day). Tracheobronchial lavage samples of all rats were quantitatively cultured after 3 days from the instillation. RESULTS: The colony numbers of isolated bacteria were significantly higher in cigarette smoke-treated rats than in the control group and in the smoke- and vitamin E-supplemented rats (P < 0.05). Only S. aureus and S. epidermidis were isolated from vitamin E-supplemented rats, while instilled all six bacterial species were isolated from the other two groups. CONCLUSIONS: It is concluded that smoking impairs the elimination of bacteria or facilitates colonization of bacteria in the lower respiratory tract of rats. Supplementary treatment with vitamin E reduces the effect of cigarette smoke; however, some bacteria may be resistant to this action of vitamin E.     

Clusterin decreases oxidative stress in lung fibroblasts exposed to cigarette smoke

RATIONALE: Cigarette smoke causes injury to lung fibroblasts, partly by means of oxidative stress, and oxidative stress can lead to various lung diseases, such as chronic obstructive pulmonary disease. Clusterin is a widely distributed protein with many functions, including cellular protection in response to oxidative stress. OBJECTIVES: To determine whether clusterin is involved in the defense of the lung against cigarette smoke, we investigated the effects of cigarette smoke extract on clusterin expression and its protective effect, if any, against oxidative stress. METHODS: Fibroblasts were coincubated with conditioned medium and cigarette smoke extract, and bronchial biopsy specimens obtained from nonsmokers, smokers, and ex-smokers were analyzed by immunohistochemistry. Measurements and Main Results: At concentrations of 2.5 and 5.0%, cigarette smoke extract induced oxidative stress. It also markedly increased the expression of two clusterin isoforms (60 and 76-80 kD) and the 76-80-kD isoform was secreted in the incubation medium. Coincubation of fibroblasts with conditioned medium significantly decreased the cellular oxidation caused by the cigarette smoke extract. Immunohistochemical analysis of clusterin on bronchial biopsy specimens obtained from smokers and ex-smokers showed localization of clusterin mainly in the submucosa. CONCLUSIONS: We conclude that clusterin may have a protective effect against cigarette smoke-induced oxidative stress in lung fibroblasts.     

硒和维生素E对大鼠心肌腺苷酸及氧化损伤的影响

目的：研究低硒（Ｓｅ）低维生素Ｅ（ＶＥ）饮食大鼠心肌腺苷酸含量和氧化损伤的关系。方法：使用高效液相测定心肌腺苷酸含量和使用生化方法测定心肌ＭＤＡ含量和ＳＯＤ、ＧＳＨ－Ｐｘ活性。结果：与补充Ｓｅ和／或ＶＥ饮食大鼠相比，低Ｓｅ低ＶＥ饮食大鼠心肌ＡＭＰ，ＡＤＰ含量无明显差异，而ＡＴＰ含量明显降低，ＭＤＡ含量增加，ＳＯＤ，ＧＳＨ－Ｐｘ活性降低，表明Ｓｅ和ＶＥ影响ＡＴＰ含量与其抗氧化作用有关，而其中以联合补充Ｓｅ和ＶＥ效果最佳     

Vitamin E deficiency alters the in vivo Rb+ discrimination of rat brain cortical cells

The in vivo Rb+ uptake and release of rat brain cortical cells of 11-months-old rats fed with a vitamin E deficient diet was investigated. The animals were treated with a daily dose of 30 mg RbCl/100 g body weight for 14 days. After discontinuation of the RbCl treatment the animals were killed at intervals of 2, 4, 9 and 15 days, respectively. The intracellular Rb+ and K+ contents were analyzed by energy dispersive X-ray microanalysis, whereas concentrations of these two ions were determined by atomic absorbtion spectrophotometry in the serum and cerebrospinal fluid. Vitamin E deficient rats accumulate more Rb+ than age-matched normally fed animals at any time taken into account. Rb+-discrimination ratios calculated on the basis of Rb+ and K+ contents of both, cortical cell cytoplasm and cerebrospinal fluid, are higher in vitamin E deficient rats than in the controls (+20%), which supports the view that the enhanced membrane lipid peroxidation induced by vitamin E deficiency impairs the passive membrane permeability for Rb+ (and K+).     

Cigarettes and cigarette smoking.

Tobacco use was widespread in the New World by the time of the first voyage of Columbus; however, it is only in the last century that the use of tobacco as cigarettes has been prevalent. The milder tobacco and more acidic smoke of cigarettes lead to the deeper inhalation of tobacco into the lung with resultant deposition and absorption of the addicting, toxic, and carcinogenic components of the smoke. More than 4000 individual constituents have been identified in cigarette smoke, and the relative concentrations of these constituents vary widely between brands of cigarettes. Tar yield, a measure of the total particulate matter of the smoke, varies markedly with the characteristics of the cigarette manufacture and with the pattern of inhalation. As a result, tar is not a good measure of the dose of toxic or carcinogenic agents received by the individual smoker. The particle size of cigarette smoke is in the range that will lead to deposition in the airways and alveoli of the lung, and many of the gas-phase constituents are absorbed across the alveolar capillary membrane. The irritant agents in the smoke cause acute and chronic changes in lung structure and function that may result in greater retention of carcinogens within the lung and increased vulnerability of the lung to the effects of these carcinogens. Carcinogens and other constituents of cigarette smoke are also absorbed into the blood and metabolized to active forms through microsomal enzyme systems induced by cigarette smoke. The cellular influx of neutrophils and alveolar macrophages that is part of the inflammatory response may be the precursor of the alveolar wall destruction that results in emphysema. The prevalence of smoking is not uniformly distributed across the population. Men began smoking in large numbers very early in the century, but women began to smoke in large number only at the time of the Second World War. Men born after 1930 have been less likely to take up smoking than their older counterparts. The prevalence of smoking is currently declining in both men and women.