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Free radicals and tobacco smoke

Free radicals and tobacco smoke

They tobaccco noted that cigarette smoke exposure caused oxidation Prevents cross-contamination plasma protein thiols sjoke and cysteine Free radicals and tobacco smoke acid linkages and Frree density lipo-proteins. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. See Our Editorial Process. The actives may be incorporated in micro-encapsulation vehicles such as liposomes, glycospheres and nonospheres. Identifying smokers at risk of COPD and GOLD.

Free radicals and tobacco smoke -

IN attempts to determine a unifying principle of action for the many and varied carcinogenic agents, many workers have assigned an intermediary role to free radicals.

The action of ionizing radiation and radiomimetic agents in this respect has been discussed by Brues and Barron 1.

It is stated that many, if not all, carcinogens are compounds capable of forming free radicals which may be stabilized as ions 2. Oppenheimer et al. This is a preview of subscription content, access via your institution.

Brues, A. Article Google Scholar. Oppenheimer, B. Article ADS Google Scholar. CAS PubMed Google Scholar. Ingram, D. Google Scholar. and Indust. Steiner, P. Download references.

Cancer Research Department, Royal Beatson Memorial Hospital, Glasgow. You can also search for this author in PubMed Google Scholar. Reprints and permissions.

LYONS, M. Free-Radicals produced in Cigarette Smoke. Nature , — Download citation. Issue Date : 05 April Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

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Skip to main content Thank you for visiting nature. nature letters article. Abstract IN attempts to determine a unifying principle of action for the many and varied carcinogenic agents, many workers have assigned an intermediary role to free radicals.

Access through your institution. Buy or subscribe. Change institution. Learn more. application Ser. The present invention can be employed in filter cigarettes, unfiltered cigarettes, cigars, pipes, and smokeless tobacco products. The deleterious effects of tobacco abuse are well known and regulatory agencies as well as the public constantly react to these scientific and epidemiologic evidences.

Tobacco is indeed a worldwide public health hazard accounting for significant morbidity and mortality. Although smoking places an abundant oxidant insult to the oral cavity, respiratory tract and lungs, evidence supports the notion that the oxidant burden is on the entire organism of the smoker.

Tobacco is a substance consisting of the dried leaves and stems of the plant Nicotiana tabacum. Tobacco contains the drug nicotine, which is very addictive. The plant is native to North America and now is grown worldwide. Tobacco abuse has been identified as the single most preventable cause of disease, morbidity and mortality, for tobacco smoke contains many toxic chemicals, in tar and gas phase smoke.

There are three principal ways to consume tobacco: 1 smoking, 2 chewing and dipping, and 3 snuffing. Fifty million Americans smoke, and countless others are affected by tobacco smoke, the so called secondary or environmental smokers. Children of smokers also breathe this second-hand smoke and have more respiratory problems than children of non-smokers.

Smokeless tobacco is used by as many as 12 million individuals and has detrimental effects on the oral cavity plus systemic effects derived from buccal absorption of nicotine and other chemicals.

Cigarette smoke is divided into two phases, tar and gas-phase smoke. Cigarette tar contains high concentrations of free radicals. Common oxidants include semiquinone which is in equilibrium with hydroquinones and quinones, particularly in the viscous tar matrix.

Many tar extracts and oxidants, including the latter mentioned, are water soluble and reduce oxygen to its superoxide radical which can dismutate to form H 2 O 2. Importantly, glass-fiber type cigarette filters retain almost all of the tar particles that are larger than 0. Thus, the filter acts as a trap for tars in cigarette smoke.

There are an inordinately large number of free radicals, greater than 10 15 , in each puff in the gas-phase of cigarette smoke. While oxidants in tar are stable, those organic radicals in gas phase smoke are reactive carbon and oxygen centered radicals with extremely short half lives.

Other free radical species, such as the aldehyde species have longer half-lives and may be more deleterious, resulting from lipid peroxidation.

Interestingly, concentrations of free radicals from tobacco are maintained at high levels for more than 10 minutes and tend to increase as tobacco smoke is aged. It is thus considered that these gas phase smoke oxidants are in a steady state as they are both continuously formed and destroyed.

The latter reactions are similar to those noted to occur in smog, pointing to the extra noxious stimuli to primary and secondary smokers in atmospheric polluted environments. Various studies have correlated the importance of oxidant stress to various organs resulting from tobacco smoke and other noxious environmental factors and thus continue to exert a toll on the public health of all countries.

Significant morbidity and mortality result from smoking tobacco from cigarettes, cigars, and pipes and local oral pathology from both smoking and chewing tobacco. Epidemiologic studies have strongly implicated tobacco in the pathogenesis of atherosclerosis and coronary artery disease, emphysema and various malignancies, including oro-pharyngeal and pulmonary neoplasias.

Chronic cigarette smoking is associated with appearance of free radicals inducing oxidative damage. Measurement in blood, urine and tissues of various antioxidants or of by-products of free radical metabolic processes are supportive of tissue oxidant damage in the pathogenesis of various diseases associated with tobacco smoking and environmental pollutants.

Studies have estimated that tobacco smoke has over 3, different constituents, of which a number are toxic, some are carcinogenic and many generate free radical species. Most of these compounds have been identified in so-called mainstream and sidestream tobacco smoke. The former is that volume of smoke drawn through the mouthpiece of the tobacco product during puffing while sidestream smoke is that smoke emitted from the smoldering cigarette in between puffs.

Although tar and nicotine are retained in the filter of cigarettes, the present invention applies mainly to mainstream smoke, be it drawn through filtered and non-filtered cigarettes. It is noted that the emissions of toxic and carcinogenic components in sidestream smoke are not significantly reduced in filter cigarettes when compared to their non-filter counterparts.

Thus, sidestream smoke is a major contributor to environmental smoke, affecting both the smoker and their non-smoking counterparts, so called secondary smokers.

The lower rates of consumption of cigarettes with high smoke yields has not reduced the indoor pollutants of carcinogenic substances and free radicals generating potential of tobacco smoke produced in sidestream smoke, albeit their diminished levels in mainstream smoke by smoking low yield tobaccos and filtered cigarettes.

Leukoplakia, a tobacco induced white patch on the buccal mucosa, as found in smokers, is a localized irritation due to direct contact of smoked tobacco and it is directly related to the frequency and years of tobacco abuse. Although leukoplakia is a benign oral lesion, these have a malignant potential, requiring a biopsy of the lesion to rule out cancer.

Leukoplakia may regress or resolve completely when use of tobacco products is discontinued. Over 30, new cases of cancer of the oral cavity are diagnosed annually, accounting for two to four percent of all new cancers. Oral cancer kills 8, patients each year and only half of cases diagnosed annually have a five year survival.

The great majority of these patients are users of tobacco products. Other risk factors include alcohol abuse, nutritional deficiencies and poor oral hygiene. Tobacco contributes to other oral symptoms or pathologies of the mouth and teeth. Tobacco may cause halitosis, may numb the taste buds, interfere with the smell and the taste of food and may stain teeth and contribute to dental caries.

For example, smokers have more dental tartar calculus than non-smokers. Tobacco is also associated with destructive periodontal gum disease and tooth loss. Tobacco, whether smoked as cigarettes, cigars or pipes causes common untoward effects in the oral cavity. Tobacco smoke has two chances to exert its deleterious effects in the mouth—when it is inhaled by the smoker and on its exit during exhalation.

Like cigarettes, evidence shows that cigars are also toxic and addictive. Cigar and cigarette smokers have a similar increased risk for oral and laryngeal cancers but the latter smokers are more prone to contract cancer of the lung, emphysema and cardiovascular disease.

While cigarette tobacco is generally flue cured with a resulting mildly acidic product, the slower curing methods for cigars render these mildly alkaline. At this pH, nicotine is more readily absorbed. Unlike cigarettes, cigars are less homogenous and vary in size and nicotine content.

Cigar smokers also commonly hold an unlit cigar in the mouth, exposing the oral cavity to further nicotine by local absorption. Thus, consumption of cigars may produce an equal or greater smoke burden of exposure and locally generated free radicals in the oral cavity which create deleterious effects and a risk of oro-pharyngeal cancer.

Carcinoma of the lung and chronic lung disease have been known to be end stage complications of cigarette abuse. Nicotine tars contain carcinogens and smoking also induces a free radical reaction in the respiratory tract, both putative to the oro-pharyngeal and pulmonary diseases and neoplasias induced by tobacco abuse.

Epidemiologic studies have been done in various countries to show the differential effects of tar content, amount of cigarettes smoked, type of tobacco smoked, and use of filters on oro-pharyngeal and lung cancer risk in cigarette smokers. Under the epithelial lining along the respiratory airways there is a rich network of micro vessels which carry systemic blood from the nasal and tracheobronchial arteries.

These vessels provide nutrition to the mucosa to enable it to maintain the protective functions. This first line of defense initially is non-injurious and reversible, but overwhelming or chronic and persistent stimuli, as tobacco smoke and other environmental pollutants, may cause pulmonary damage from the oxidative damage of the leucocytes, other free radicals and noxious agents.

In other in vitro studies, gas-phase cigarette smoke was assessed in its filtered and whole unfiltered states for oxidative effects on human plasma. Investigators noted the prevalence of lipid peroxidation in plasma after exposure to gas phase smoke, but not to whole cigarette smoke.

The reaction of lipid peroxidation did not commence until the endogenous ascorbic acid had been consumed, that is, vitamin C was oxidized completely. They also noted that cigarette smoke exposure caused oxidation of plasma protein thiols methionine and cysteine amino acid linkages and low density lipo-proteins.

They concluded that lipid peroxidation induced by the oxidants of gas-phase smoke leads to changes in lipoproteins associated with atherogenesis.

As noted herein, the synergistic effect of reduced glutathione and ascorbic acid or ascorbic acid derivatives such as their esters, are beneficial in combating tobacco oxidants and in both ameliorating and delaying the effects of tobacco smoke on oral, pharyngeal and respiratory epithelia, on bronchoalveolar fluids and on lung parenchyma.

Cells subjected to oxidative stress may severely affect cellular function and cause damage to membrane lipids, to proteins, to cytoskeletal structures and to DNA. Free radical damage to DNA has been measured as formation of single-strand breaks, double-strand breaks and chromosomal aberrations.

Cells exposed to ionizing radiation and cigarette smoke have also been demonstrated to have an increased intracellular DNA damage, hence the frequency of oro-pharyngeal, esophageal, and pulmonary carcinomas in tobacco users. The lungs have adapted biochemical enzymatic and non-enzymatic antioxidant systems as prevention, limitation or reversal of oxidant damage to the lungs.

This is a protective feature to maintain normal pulmonary function, as the respiratory tissues operate in an environment of high partial pressure of oxygen and are continuously exposed to airborne pollutants.

Because of their access to the environment, like the skin to oxygen and ultraviolet radiation, the lungs may be damaged by inhaled gaseous and particulate matter, particularly in both active and passive smokers.

Reactive oxidizing species, as induced by inhaled tobacco, smoke, ozone smog and others are important factors in bronchial hyperresponsiveness and inflammatory lung injury. As in other tissues, antioxidant enzymes in the lung include superoxide dismutase SOD , which converts superoxide to hydrogen peroxide and catalase which reduces hydrogen peroxide to water.

This reaction may also be catalyzed by the selenium cofactor enzyme glutathione peroxidase using reduced glutathione GSH as a substrate. Glutathione peroxidase may also reduce lipid peroxide to the corresponding alcohols also using reduced glutathione.

The ubiquitous non-enzymatic thiol tripeptide, glutathione GSH , plays a vital function in maintaining the integrity of the reactive oxygen species-free radical sensitive cellular components.

This is accomplished through its direct role as an antioxidant, in its reduced GSH form, as well as a cofactor, as aforementioned. GSH has been detected in bronchoalveolar lavage fluid.

In cells, GSH is oxidized in this process to GSSG, but its cellular concentrations for antioxidant activity is maintained in equilibrium by the enzyme glutathione reductase, consuming NADPH as the source of reducing equivalents. Under states of GSH depletion, including malnutrition and severe oxidative stress, as in smoking, cells may become injured and die.

The solid phase tar of tobacco contains high concentrations of stable free radicals. These have been identified as semiquinones which are in equilibrium with quinones and hydroxyquinones. These free radicals are capable then of reducing molecular oxygen to form the toxic free radical called superoxide.

Superoxide, upon dismutation, can form the injurious molecule hydrogen peroxide H 2 O 2. However, gas-phase smoke contains over 10 15 organic radicals per each puff. In contrast to stable free radicals, these have a half-life of 1 second yet are capable of maintaining their high levels of activity in the gas phase smoke for over 10 minutes.

This smoke also results in the creation of the H 2 O 2 through the smoke's production of the toxic hydroxyl radical. The present invention recognizes that the enzyme superoxide dismutase reduces the toxicity of the hydroxyl radical by the dismutation reaction to make the relatively less toxic H 2 O 2.

However, to reduce H 2 O 2 and other peroxide molecules, the enzymes catalase and glutathione peroxidase are required. The former, catalase, reduces H 2 O 2 to water and O 2. Hydrogen peroxide, like other tobacco generated free radicals, have been implicated in the etiology of oro-pharyngeal malignancy and pulmonary neoplasms, in smokers.

H 2 O 2 reacts with the DNA in cells and causes breaks in the double strand which lead to mutations, precursors of malignant cells. Cigarette smoke also contains aldehydes which are capable of altering protein function by increasing the rate of catabolism.

This is the hallmark lesion that results in coronary heart, cerebrovascular and peripheral vascular diseases. The aldehydes cause these alterations in proteins by their carbonyl group reacting with the thiols and NH 2 moieties of the plasma proteins.

The present invention involves the inclusion of an antioxidant defense system within a filter to be used with tobacco products or within tobacco or within a wrapper for such tobacco products or as applied to smokeless tobacco.

The present application utilizes synergistic antioxidants delivered, for example, in tobacco filters such as those for cigarettes or external filters to prevent and ameliorate free radical damage induced by smoking to the oro-pharynx, respiratory tract and lungs.

The composition is supplied by inhalation through various state of the art filters. The invention in its broadest terms comprises glutathione plus the antioxidant enzymes catalase and superoxide dismutase. The composition also may incorporate glutathione in its reduced form and a co-ingredient for regenerating the reduced form of the glutathione, the co-ingredient comprising selenium as a selenoamino acid such as selenomethionine or selenocysteine.

The lungs are very susceptible to damage caused by inhaled noxious agents rendering a response to this injury by respiratory epithelial cells and pulmonary vascular endothelium.

Bacteria, fungi and viruses may also induce pulmonary infections. All of the aforementioned evoke respiratory tissue free radical reactions and antioxidant-inflammatory responses. Teleologically, the present invention involves, as a front line defense mechanism to inhaled particles and gases and their impact upon the respiratory tract and lungs, the use of active enzymatic and non-enzymatic antioxidants to prevent, minimize, reverse and even repair this oxidant damage.

The former includes superoxide dismutase, which converts deleterious superoxide radical to hydrogen peroxide and catalase which reduces H 2 O 2 to water. This latter reaction may also be catalyzed by selenium containing glutathione peroxidase which may also reduce lipid hydroperoxides, products of oxidant induced lipid peroxidation, to alcohols, also using glutathione as the source of reducing radicals.

Thus, the thiol tripeptide, glutathione, GSH acts as a direct antioxidant and as a cofactor in reactive oxygen species defense mechanisms.

In this process, glutathione becomes oxidized but its cellular concentration as a reduced compound is maintained by the related enzyme glutathione reductase. The minerals iron and copper of the tar phase contribute to the generation of hydroxyl radicals as well and to the generation of peroxy and alkoxy free radicals and other toxic cellular aldehydes.

These radical species are scavenged and neutralized primarily by glutathione peroxidase with its selenium co-factor in the presence of the ubiquitous tripeptide reduced glutathione GSH antioxidant. Glutathione, which participates in many detoxifying defensive cellular and body fluid functions, also serves as a substrate in the removal of various metabolic intermediates such as H 2 O 2 , lipid peroxides and organic hydroperoxides by action of the enzyme, glutathione peroxidase.

This is the synergy in reducing and neutralizing toxic cigarette free radicals by superoxide dismutase, catalase, glutathione and selenium. The adminstration of the latter, selenium, has been shown not only to itself possess anticarcinogenic properties but it also induces the production of the vital enzyme, glutathione peroxidase.

In addition, GSH forms conjugates with smoke's organic free radicals through the action of the glutathione transferases. This GSH mechanism also works in excreting ingested environmental pollutants. During the process of smoking, pulmonary alveolar macrophages release both superoxide and nitrous oxide.

Peroxynitrite appears in greater amounts in the exhaled smoke than in the inhaled smoke. Thus, it is important to reduce the inhalation of superoxide and NO by antioxidants in tobacco products, particularly in the filter of the cigarette, as well as to provide the smoker's body with supplemental antioxidants to help neutralize these oxygen intermediates and the other free radical species inhaled and created by tobacco products.

Superoxide dismutase, importantly, catalyzes nitration by peroxynitrite and also catalyzes phenolic compounds, including tyrosine, in protein molecules. Thus, SOD helps reduce the body's oxidative stress induced by smoking, particularly that caused by superoxide and peroxynitrites.

Fractionation of aqueous cigarette tar extracts contain tar radicals that cause damage to DNA. By special analysis, these tar extracts have been identified as catechols and hydroquinones. Aqueous tar extracts that cause damage to DNA produce the reactive oxygen intermediates including superoxide, H 2 O 2 and hydroxyl radicals.

The enzyme catalase inhibits some of this damage, indicating that H 2 O 2 is the precursor of the hydroxyl radical emanating from tar extracts, responsible at least in part for cigarette smoke's damage to DNA and thereby etiologic of malignancy. See Pryor, et al, Chem Reseach in Toxicology Other non-enzymatic molecules playing an antioxidant role in the lung include the ascorbates vitamin C ; particularly in the extracellular defenses of the lung, as teleologically, it is present in high concentrations in the pulmonary airway lining fluid.

Ascorbates as free radical scavengers also react with oxidized glutathione GSSG to reduce it to GSH. Also, in the lipid membrane of the cells, the hydrophobic alpha-tocopherols vitamin E , act synergistically with vitamin C to inhibit lipid peroxidation, as may be induced by cigarette smoke, by actively scavenging lipid peroxides and other free radicals.

The compositions of the present invention can be incorporated in various smoking products. Examples include, but are not limited to, U.

This patent teaches that the method provides stability over the length of time before the cigarette is smoked. As taught in U. Prior to lighting up, pressure is applied to the putative capsule, so that the released active materials are dispersed within the filter, thereby the Vitamin A is accessible to the cigarette smoke passing through.

The ' patent further teaches that stabilized Vitamin A may also be dispersed, impregnated in the tobacco or provided throughout in droplets or beadlets through the employment of gelatin or other colloidal materials, so that the stabilized Vitamin A can be easily entrained by the smoke passing through the filtering elements.

Thus, dispersed and random distribution of the small liquid droplets or tiny particulate matter of the Vitamin A preparation is located throughout the tobacco proper or throughout the filtering medium of a filter cigarette.

The Vitamin A is surrounded and protected in a method akin to micro-encapsulation. Irimi and coworkers taught in U. One such component contains an enediol structure. The ' patent points out that the synergistic compositions eliminate the excited formaldehyde radical from the tobacco smoke.

It has been noted that tar in smoke may be reduced by using low tar tobaccos and cigarette filters. Other efforts have been directed to reducing toxic and harmful substances in the tobacco itself or by adding these modifications of filters or by adding chemicals to the filters.

Caseley taught a method to further reduce aldehydes in tobacco by using non-toxic salts of w-mercapto-alkalene-sulphonates, as well as cysteine and acetylcysteine in U. These compositions were to be added to cigarette filters or cigarette holders comprising a filter for the purposes of reducing toxic tobacco substances in situ, while smoking cigarettes.

They taught the use of impregnating a granular activated carbon with a pore modifying agent, like sucrose, and thereby improve the shelf life and delivery of the smoke flavoring agent.

Effective date : Year of fee smoe : 4. Mindful eating practices composition for inclusion within a cigarette, racicals, pipe or smokeless tobacco. The composition can be included tobacc Free radicals and tobacco smoke tobacco itself, a filter for filtering tobacco smoke once burned within the paper or wrapper surrounding the tabacco product. In the cigarette filter, be it internal or external filters, the antioxidant complex is capable of scavenging and neutralizing the free radicals emanating from the burning or heated tobacco and passing through the filter as the smoker inhales. The aim of this study is tboacco evaluate smoking-induced nitrosative and oxidative stress and the role of hypoxia inducible factor Artisanal Food Products alpha HIF-1α in erythrocytes smoek platelets. For Coenzyme Q and fertility study human Free radicals and tobacco smoke volunteers aged ravicals Free radicals and tobacco smoke were recruited and divided into two groups, namely controls and smokers 12±2 cigarettes per day for years. Blood was collected and analyzed for various metabolites and enzymes. Results showed a decreased plasma vitamin C and reduced glutathione GSH with increased lipid peroxidation, carbonyl groups, iron, hemoglobin and glycated hemoglobin content in smokers. Moreover, smokers showed diminished GSH and the activities of superoxide dismutase SOD glutathione peroxidase GPx and catalase CAT in both erythrocytes and platelets compared to controls.

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Detecting \u0026 Scavenging Gas-Phase Free Radicals In Mainstream Cigarette Smoke l Protocol Preview

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