1. in the environment although anthropogenic activities are

1.   INTRODUCTION. An air pollutant is any substance which may harm humans, animals,vegetation or material. A number of physical activities (volcanoes, fire, etc.)may release different pollutants in the environment although anthropogenicactivities are the major cause of environmental air pollution. Hazardouschemicals can escape to the environment by accident, but a number of airpollutants are released from industrial facilities and other activities and maycause adverse effects on human health and the environment (CEE,2012).Air pollutants include suspended particles and gases including carbonmonoxide, volatile organic compounds (VOCs), nitrous oxides, sulphur dioxide,and ozone.

Suspended particles are called particulate matter (PM), which is a mixtureof tiny particles and liquid droplets that includes acids, organic chemicals,metals, and dust. PM is measured by size: PM2.5 is 2.5 micrometres (?m) in diameter.For comparison, a human hair is 70?m in diameter.As far as humans are concerned an air pollutant may cause orcontribute to an increase in mortality or serious illness or may pose a presentor potential hazard to human health. The determination of whether or not asubstance poses a health risk to humans is based on clinical, epidemiological,and/or animal studies which demonstrate that exposure to a substance isassociated with health effects. In the context of human health, ”risk” is theprobability that a noxious health effects may occur.

                           2.PollutantcategoriesThe main change in the atmospheric composition is primarily due tothe combustion of fossil fuels, used for the generation of energy andtransportation. Variant air pollutants have been reported, differing in theirchemical composition, reaction properties, emission, persistence in theenvironment, ability to be transported in long or short distances and theireventual impacts on human and/or animal health.

However, they share somesimilarities and they can be grouped to four categories: a. Gaseous pollutants (e.g. SO2, NOx,CO, ozone, Volatile Organic Compounds) b. Persistent organic pollutants (e.

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g. dioxins). c. Heavy metals (e.g. lead, mercury). d.

Particulate Matter.a)   Gaseous pollutants contribute to a great extent incomposition variations of the atmosphere and are mainly due to combustion offossil fuels (Katsouyanni, 2003). nitrogen oxides are emitted from fossilfuel burning and ammonia is emitted from agricultural activities. Nitrogen is anutrient and its increased deposition affects plant biodiversity. In addition,nitrogen contributes to acidification of soils and waters. Nitrogen oxides areemitted as NO which rapidly reacts with ozone or radicals in the atmosphereforming NO2.

The main anthropogenic sources are mobile and stationarycombustion sources. Moreover, ozone in the lower atmospheric layers is formed by aseries of reactions involving NO2 and volatile organic compounds, a processinitiated by sun light. CO, on the other hand, is a product of incompletecombustion.

Its major source is road transport too. While the anthropogenic SO2 emitted from fossil fuel burning(industry, households, transport), sulphur dioxide causes acidification ofsoils, streams and lakes and leads to erosion of building materials, includingcultural heritage. volcanoes and oceans are its major natural sources. Thelatter contribute only ~2% of the total emissions.

Finally, a major class of compounds that fuel combustion andespecially combustion processes for energy production and road transport arethe major source of emission are the so called volatile organic compounds(VOCs). Volatile organic compounds (VOCs) are emitted as gases from certainsolids or liquids. VOCs include a variety of chemicals, some of which may haveshort- and long-term adverse health effects. They are compounds that have ahigh vapor pressure and low water solubility. Many VOCs are human-madechemicals that are used and produced in the manufacture of paints, pharmaceuticals,and refrigerants.VOCs typically are industrial solvents, such as trichloroethylene;fuel oxygenates, such as methyl tert-butyl ether (MTBE); or by-productsproduced by chlorination in water treatment, such as chloroform. VOCs are oftencomponents of petroleum fuels, hydraulic fluids, paint thinners, and drycleaning agents. (EPA, 2006) b)   Persistent organic pollutants – Persistent organicpollutants (POPs) are chemicals of global concern due to their potential forlong-range transport, persistence in the environment, ability to bio-magnifyand bio-accumulate in ecosystems, as well as their significant negative effectson human health and the environment.

Humans are exposed to these chemicals in avariety of ways: mainly through the food we eat, but also through the air we breathe,in the outdoors, indoors and at the workplace. Many products used in our dailylives may contain POPs, which have been added to improve productcharacteristics, such as as flame retardants or surfactants. As a result, POPscan be found virtually everywhere on our planet in measurable concentrations.The most commonly encountered POPs are organochlorine pesticides,such as DDT, industrial chemicals, most notably polychlorinated biphenyls(PCB), as well as unintentional by-products of many industrial processes,especially polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF),commonly known as ‘dioxins’.

POPs bio-magnify throughout the food chain and bio-accumulate inorganisms. The highest concentrations of POPs are thus found in organisms atthe top of the food chain. Consequently, background levels of POPs can be foundin the human body.Human exposure – for some compounds and scenarios, even to lowlevels of POPs – can lead, among others, to increased cancer risk, reproductivedisorders, alteration of the immune system, neurobehavioural impairment,endocrine disruption, genotoxicity and increased birth defects.  c)   Heavy metals The term heavy metal refers to anymetallic chemical element that has a relatively high density and is toxic orpoisonous at low concentrations.

Examples of heavy metals include mercury (Hg),cadmium (Cd), arsenic (As), chromium (Cr), thallium (Tl), and lead (Pb). Heavymetals are natural components of the Earth’s crust. They cannot be degraded ordestroyed.

To a small extent they enter our bodies via food, drinking water andair. As trace elements, some heavy metals (e.g. copper, selenium, zinc) areessential to maintain the metabolism of the human body. However, at higherconcentrations they can lead to poisoning. Heavy metal poisoning could result,for instance, from drinking-water contamination (e.

g. lead pipes), high ambientair concentrations near emission sources, or intake via the food chain. Heavy metals are dangerous because they tend to bio accumulate.Bioaccumulation means an increase in the concentration of a chemical in abiological organism over time, compared to the chemical’s concentration in theenvironment. Compounds accumulate in living things any time they are taken upand stored faster than they are broken down (metabolized) or excreted. Heavymetals can enter a water supply by industrial and consumer waste, or even fromacidic rain breaking down soils and releasing heavy metals into streams, lakes,rivers, and groundwater. d)    Particulate matter (PM) – Particulate Matter (PM) includes both solid particles and liquiddroplets found in air. Many man-made and natural sources emit PM directly oremit other pollutants that react in the atmosphere to form PM.

These solid andliquid particles come in a wide range of sizes. Particles less than 10 micrometresin diameter tend to pose the greatest health concern because they can beinhaled into and accumulate in the respiratory system. Particles less than 2.5 micrometresin diameter are referred to as “fine” particles. Sources of fineparticles include all types of combustion (motor vehicles, power plants, woodburning, etc.) and some industrial processes. Particles with diameters between2.

5 and 10 micrometres are referred to as “coarse”. Sources of coarseparticles include crushing or grinding operations, and dust from paved orunpaved roads.The Environmental Protection Agency uses its Air Quality Index toprovide general information to the public about air quality and associatedhealth effects. An Air Quality Index (AQI) of 100 for any pollutant correspondsto the level needed to violate the federal health standard for that pollutant.For PM2.5, an AQI of 100 corresponds to 40 micrograms per cubic meter (averagedover 24 hours) — the current federal standard. An AQI of 100 for PM10corresponds to a PM10 level of 150 micrograms per cubic meter (averaged over 24hours).

                                 3. Routes of exposureHumans enter in contact with different air pollutants primarily viainhalation and ingestion, while dermal contact represents a minor route ofexposure. Air pollution contributes, to a great extent, to the contamination offood and water, which makes ingestion in several cases the major route ofpollutant intake (Thron, 1996).

Via the gastrointestinal and respiratory tract,absorption of pollutants may occur, while a number of toxic substances can befound in the general circulation and deposit to different tissues. Eliminationoccurs to a certain degree by excretion (Madden and Fowler, 2000).                                         4.

Health effectsSporadic air pollution events, like the historic London fog in 1952and a number of short and long term epidemiological studies investigated theeffects of air quality changes on human health. A constant finding is that airpollutants contribute to increased mortality and hospital admissions(Brunekreef and Holgate, 2002). The different composition of air pollutants,the dose and time of exposure and the fact that humans are usually exposed topollutant mixtures than to single substances, can lead to diverse impacts onhuman health. Human health effects can range from nausea and difficulty inbreathing or skin irritation, to cancer.

They also include birth defects,serious developmental delays in children, and reduced activity of the immunesystem, leading to a number of diseases. Moreover, there exist severalsusceptibility factors such as age, nutritional status and predisposingconditions. Health effects can be distinguished to acute, chronic not includingcancer and cancerous. Epidemiological and animal model data indicate thatprimarily affected systems are the cardiovascular and the respiratory system.

However,the function of several other organs can be also influenced (Cohen et al.,2005; Huang and Ghio, 2006; Kunzli and Tager, 2005; Sharma and Agrawal, 2005). 4.1. Effects of air pollutants on different organs and systems 4.1.1. Respiratory systemNumerous studies describe that all types of air pollution, at highconcentration, can affect the airways.

Nevertheless, similar effects are alsoobserved with long-term exposure to lower pollutant concentrations. Symptomssuch as nose and throat irritation, followed by bronchoconstriction anddyspnoea, especially in asthmatic individuals, are usually experienced after exposureto increased levels of sulphur dioxide (Balmes et al., 1987), nitrogen oxides(Kagawa, 1985), and certain heavy metals such as arsenic, nickel or vanadium.In addition, particulate matter that penetrates the alveolar epithelium (Ghio andHuang, 2004) and ozone initiate lung inflammation (Uysal and Schapira, 2003).In patients with lung lesions or lung diseases, pollutant-initiated inflammationwill worsen their condition. Moreover, air pollutants such as nitrogen oxides increasethe susceptibility to respiratory infections (Chauhan et al., 1998). Finally,chronic exposure to ozone and certain heavy metals reduces lung function(Rastogi et al.

, 1991; Tager et al., 2005), while the later are alsoresponsible for asthma, emphysema, and even lung cancer (Kuo et al., 2006; Nawrotet al.

, 2006). Emphysema-like lesions have also been observed in mice exposedto nitrogen dioxide (Wegmann et al., 2005). 4.1.

2. Cardiovascular systemCarbon monoxide binds to haemoglobin modifying its conformation andreduces its capacity to transfer oxygen (Badman and Jaffe, 1996). This reducedoxygen availability can affect the function of different organs (and especiallyhigh oxygenconsuming organs such as the brain and the heart), resulting inimpaired concentration, slow reflexes, and confusion. Apart from lunginflammation, systemic inflammatory changes are induced by particulate matter,affecting equally blood coagulation (Riediker et al., 2004). Air pollution thatinduces lung irritation and changes in blood clotting can obstruct (cardiac)blood vessels, leading to angina or even to myocardial infraction Vermylen etal., 2005). Symptoms such as tachycardia, increased blood pressure and anaemiadue to an inhibitory effect on haematopoiesis have been observed as aconsequence of heavy metal pollution (specifically mercury, nickel and arsenic)  (Huang and Ghio, 2006).

Finally,epidemiologic studies have linked dioxin exposure to increased mortality causedby ischemic heart disease, while in mice, it was shown that heavy metals canalso increase triglyceride levels (Dalton et al., 2001). 4.1.3. Nervous system          The nervous system is mainly affected by heavy metals (lead,mercury and arsenic) and dioxins. Neurotoxicity leading to neuropathies,with symptoms such as memory disturbances, sleep disorders, anger,fatigue, hand tremors, blurred vision, and slurred speech, have beenobserved after arsenic, lead and mercury exposure (Ewan and Pamphlett,1996; Ratnaike, 2003).

Especially, lead exposure causes injury to thedopamine system, glutamate system, and N-methyl-D-Aspartate (NMDA) receptorcomplex, which play an important role in memory functions (Lasley andGilbert, 2000; Lasley et al., 2001). Mercury is also responsible forcertain cases of neurological cancer. Dioxins decrease nerve conductionvelocity and impaired mental development of children (Thomke et al.,1999; Walkowiak et al., 2001).

 4.1.4. Urinary systemHeavy metals can induce kidney damage such as an initial tubulardysfunction evidenced by an increased excretion of low molecular weightproteins, which progresses to decreased glomerular filtration rate (GFR). In addition,they increase the risk of stone formation or nephrocalcinosis (Damek-Poprawa andSawicka-Kapusta, 2003; Jarup, 2003; Loghman-Adham, 1997) and renal cancer(Boffetta et al.

, 1993; Vamvakas et al., 1993). 4.1.5.

Digestive systemDioxins induce liver cell damage (Kimbrough et al., 1977), asindicated by an increase in levels of certain enzymes in the blood (seefollowing discussion on the underlying cellular mechanisms of action), as wellas gastrointestinal and liver cancer (Mandal, 2005). 4.2.

Exposure during pregnancyIt is rather important to mention that air pollutants can also affectthe developing foetus (Schell et al., 2006). Maternal exposure to heavy metalsand especially to lead, increases the risks of spontaneous abortion and reducedfetal growth (preterm delivery, low birth weight). There are also evidences suggestingthat parental lead exposure is also responsible for congenital malformations(Bellinger, 2005), and lesions of the developing nervous system, causingimportant impairment in new-born’s motor and cognitive abilities (Garza et al.,2006).Similarly, dioxins were found to be transferred from the mother tothe fetus via the placenta.

They act as endocrine disruptors and affect growthand development of the central nervous system of the foetus (Wang et al.,2004). In this respect, TCDD is considered as a developmental toxin in allspecies examined.      5. Cellular mechanisms involved in air pollutants actions Common cellular mechanism by which most air pollutants exert theiradverse effects is their ability to act directly as prooxidants of lipids andproteins or as free radicals generators, promoting oxidative stress and theinduction of inflammatory responses (Menzel, 1994; Rahman and MacNee, 2000).

Free radicals (reactive oxygen and nitrogen species) are harmful to cellularlipids, proteins, and nuclear- or mitochondrial- DNA, inhibiting their normalfunction (Valko et al., 2006). In addition, they can interfere with signalingpathways within cells (Valko et al., 2006).

In eukaryotic aerobic organismsincluding humans, free radicals are continuously generated during normalmetabolism and in response to exogenous environmental exposures (e.g.irradiation, cigarette smoke, metals and ozone). When free radicalconcentration increases, due to an overwhelming of organism’s defense, a stateof oxidative stress occurs.

This oxidative state has been implicated ina wide variety of degenerative diseases such as atherosclerosis, heart attacks,stoke, chronic inflammatory diseases (rheumatoid arthritis), cataract, centralnervous system disorders (Parkinson’s, and Alzheimer’s disease), age relateddisorders and finally cancer.Furthermore, the toxic effects of heavy metals, apart from inducingoxidative stress, can be also attributed to their ability to substitute diversepolyvalent cations (calcium, zinc, and magnesium) that function as chargecarriers, intermediaries in catalysed reactions, or as structural elements inthe maintenance of protein conformation. Indeed, metals accumulate in cellularorganelles and interfere with their function.

For example, it has been observedthat lead accumulation in mitochondria induces several changes such asinhibition of Ca2þ uptake, reduction of the transmembrane potential, oxidationof pyridine nucleotides, and a fast release of accumulated Ca2þ (Chavez et al.,1987). Moreover, metals bind to proteins (Goering, 1993) and inhibit a largenumber of enzymes, including the mitochondrial ones (Rossi et al., 1993).

Nucleic acid binding proteins are also involved, while it has been shown thatmetals can also bind to DNA, affecting the expression of genes. For example,nickel enters the nucleus, interacts with chromatin and silences the expressionof genes such as tumour suppressor genes, inducing carcinogenesis (Costa et al.,2003).

Finally, some metals interfere with various voltage- and ligand-gatedionic channels exerting neurotoxic effects.For instance, lead affects the N-methyl-D-aspartic acid (NMDA)receptor, subtypes of voltage- and calcium-gated potassium channels,cholinergic receptors and voltage-gated calcium channels (Garza et al., 2006;Toscano and Guilarte, 2005).Dioxin causes a broad range of adverse effects (Birnbaum, 1994):they alter metabolism by inducing a number of metabolic enzymes (e.g. CYPs,glutathione-transferase, tyrosine kinase etc.

), homeostasis, through hormonemodulation (e.g. estrogens, androgens glucocorticoids, insulin, thyroidhormones) and their receptors, and growth and differentiation by interferingwith growth factors (e.g. EGF, TGFa, TNFa) and their receptors. At the cellularlevel, dioxins interact with the aryl hydrocarbon receptor (AhR) (Schwarz etal., 2000) which has a basic helix-loop-helix domain, acting as a transcriptionfactor after nuclear translocation, allowing interaction of dioxins with DNA.

The receptor-ligand complex binds to specific sites on DNA, altering theexpression of a number of genes.As far as cancer is concerned from the data presented above itbecomes clear that most pollutants play an important role in the initiation,promotion and progression of cancer cells (Fig. 1).    6.

Natural protectionIn our day-to-day life we are exposed in different kinds of pollutants.Health impacts, as already described above, depend on the pollutant type, itsconcentration, length of exposure, other coexisting pollutants and individualsusceptibility. People living in cities are exposed to a greater extent, as aconsequence of increased industrialization and demands for energy and motorvehicles. Occupational exposure is also an important factor that should betaken into consideration.

During the last decade, health effects of airpollution are studied more in developed countries, while more and betterenvironmental monitoring data are required in order to setup threshold levels.In addition, efforts should be intensified by taking the appropriate measures,in order to reduce the possibility of human pollutant exposure. The human body,in order to protect itself against the potential harmful insults from theenvironment, is equipped with drug or xenobiotic metabolising enzymes (DMEs orXMEs) that play a central role in the biotransformation, metabolism and/ordetoxification of xenobiotics or foreign compounds, including different kindsof pollutants. XMEs include a variety of enzymes such as cytochrome P450 (P450or CYP), epoxide hydrolase, glutathione transferase,UDP-glucuronosyltransferase, sulfotransferase, NAD(P)H quinone oxidoreductase1, and aldo-keto reductase. These enzymes mainly participate in the conversionof xenobiotics to more polar and water-soluble metabolites, which are readilyexcreted from the body.

Finally, it should be noted that, in many cases, thechemically reactive metabolites produced during metabolism, are equally harmfuland therefore undergo additional metabolism to inactive products.Hence, the final outcome of a compound modulating thedetoxification enzyme systems is the result the effects on the differentmetabolic pathways. A number of substances of dietary nature are beneficial,protective, and supportive of good health and the body’s own natural chelationmechanisms. They include nutrients with natural chelating properties, which mayhelp to detoxify the body, such as antioxidants, herbs, minerals, essentialamino acids, other detoxifying or protective agents, and fiber (Kelly, 2004).Among them dietary antioxidants contribute to the organism’s antioxidantdefence system, that includes a series of antioxidant enzymatic (e.g.

peroxidase) and nonenzymatic compounds (such as glutathione, or food-derivedlike vitamin E, or polyphenols), as well as damage removal / repair enzymes.Several natural compounds, such as vitamins C, E, and A andpolyphenols, found in the majority of plant foods, interfere with or scavengeROS concentration within cells and subsequently protect the organism from theadverse effects of oxidative stress. Indeed, as it has been shown by our groupthat the antioxidant activity of plasma in humans following a diet rich invegetables, fruits and olive oil was increased in comparison to a normal diet(Kampa et al.

, 2002). This increase can be mainly attributed to polyphenolswhich exhibit a wide range of biological activities, includinganti-tumorigenic, anti-mutagenic, anti-inflammatory, and antiviral actions(Bravo, 1998; Hertog and Hollman, 1996) mainly due to their antioxidantproperties and their ability to exert inhibitory effects by affecting basiccellular functions. Indeed, the beneficial role of polyphenols in preventingcancer can be in part attributed to their ability to modify enzymes thatactivate or detoxify environmental carcinogens.       7. Conclusion This brief review presents the adverse effects of a number of (air)pollutants in human health. As shown, major impairments of different organs canbe observed.

The main conclusion drawn is that, in view of increased exposureof humans in a diversity of pollutants, dietary interventions, rich inplant-derived foods, may protect or decrease their effects on different organs.This conclusion is supported by a number of epidemiological studies on thebeneficial effect of a Mediterranean- type diet on human health.   


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