Chronic effect of lead and mercury on human organism
Transkrypt
Chronic effect of lead and mercury on human organism
HEALTH AND WELLNESS 1/2015 WELLNESS AND HEALTH CHAPTER XI 1 Department of Neurological Nursing, Faculty of nursing and Health Science, Medical University of Lublin Wydział Pielęgniarstwa i Nauk o Zdrowiu, Katedra i Zakład Pielęgniarstwa Neurologicznego, Uniwersytet Medyczny w Lublinie 2 Pulawy Public Hospital, Department of Paediatrics Samodzielny Publiczny Zakład Opieki Zdrowotnej w Puławach, Oddział Dziecięcy 3 Lukow Public Hospital, Department of Paediatrics Samodzielny Publiczny Zakład Opieki Zdrowotnej w Łukowie, Oddział Dziecięcy 4 Clinic of Paediatric Neurology, Faculty of Paediatrics, Medical University of Lublin Klinika Neurologii Dziecięcej, Katedra Pediatrii, Uniwersytet Medyczny w Lublinie 5 Lublin Clinical Hospital No4 in Lublin Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie MIROSŁAW JASIŃSKI1, MARCIN BRYCZEK2, MATYLDA OPOLSKA3, EWA ZIENKIEWICZ4, MAGDA CHROŚCIŃSKA-KRAWCZYK4, EWA JASIŃSKA5 Chronic effect of lead and mercury on human organism Przewlekłe oddziaływanie ołowiu i rtęci na organizm człowieka Key words: lead, mercury, methylmercury, neurotoxicity Słowa kluczowe: Ołów, Rtęć, metylortęć, Neurotoksyczność Lead is an element that does not undergo bio-degradation or decomposition, and absorbed by living organisms is accumulated in their tissues. Exposure to lead takes place by inhalation of polluted air, consumption of contaminated water and contact with polluted soil. From the air, lead is absorbed by human organism with dust. HEALTH AND WELLNESS 1/2015 Wellness and health Small diameter dust grains (under 10 μm) are more contaminated than larger (approx. 100 μm in diameter) ones. An average air lead content is approx. 0.1–0.3 μg/m in agricultural areas, 0.5 μg/m in vicinity of villages and towns, and as much as 5–3.0 μg/m in vicinity of large European cities [8, 19]. In Poland, the highest pollution occurs in areas associated with mining and metal industries, e.g. by ironworks and mines. Areas of the highest contamination level in Poland are: the Silesian district, areas of the former Opole district, and Small Poland (Małopolska). (4, 8) Lead pollution of drinking and surface water is present mostly in areas close to heavy industry plants, releasing unprocessed waste water. Considering the fact that lead compounds are not water soluble, they precipitate and sediment in silt and bottom layers. Agricultural use of nitrogen fertilisers, containing also lead, causes pollution of surface waters with the element and its compounds. The most heavily polluted areas ale located close to towns of Mysłowice, Oświęcim, Konstancin and Legnica. Attention has been recently drawn to a higher than expected effect of incorrectly welded pipelines supplying drinking water [8, 4, 17]. The highest lead content in the natural environment is in soil. That is because of the fact that lead is not bio-degraded or decomposed. The highest level of pollution is found in agricultural soil in areas associated with mining and processing of lead ore, zinc, lead and copper works (lead compounds are present in zinc and copper ores), areas around glassworks and along expressways. Currently, due to a common use of lead-free gasoline, the level of pollution in close vicinity of roads seems to be lower [4, 8]. Lead exposure from food depends mostly on soil and ground water pollution. The highest pollution levels are found in fields in areas associated with heavy industry. The presence and distance from heavy traffic roads is also important. Among vegetable products, the higher lead content is found in potatoes, and the lowest in grains. It is also important, that increased lead levels had been confirmed in livers and muscles of farm animals. That is a result of the fact that the feed for animals (ensilage, hey, corn ensilage) demonstrate high lead content [8, 10] Besides natural environment pollution, exposure to lead is also associated with lead-containing paint, and old glassware. Children are at the highest risk of that form of intoxication, e.g. because of consumption of paint chips (different behaviour than that of adults) [6, 8]. Lead absorption by a human organism: Lead is absorbed by a human organism mostly with inhaled air, drank water and ingested food. The inhalatory route is more effective compared to the gastrointestinal. An approximate lung to gastroenteral absorption rate is 10 to1. Mostly particles of <1µm are absorbed by phagocytosis. That is a result of the fact that particles of that size are able to reach alveoli. Larger particles are deposited in mucus of the upper respiratory tract and eliminated by mucocilliary clearing [14]. Absorption from the gastrointestinal tract takes place mostly due to an active transport. Passive diffusion has a minor contribution. That is due to the fact that lead contained in food is mostly present in a form of phosphate complexes, that are not transported by intestinal epithelium. Therefore, 5-10% of the total lead dose is absorbed in adults, and the remaining amount is eliminated with faeces. Those ratios are highly variable and depend on the individual's age and diet [3]. It is suspected that divalemt metal transporter (DMT1) participates in active lead transport. It was 166 Mirosław Jasiński, Marcin Bryczek, Matylda Opolska, Ewa Zienkiewicz, Magda Chrościńska-Krawczyk, Ewa Jasińska Chronic effect of lead and mercury on human organism confirmed that lead is absorbed in the duodenum (where a high level of DMT1 was demonstrated), and in ileum, where a low level of DMT1 was found. It is suspected that calbindin is responsible for the active transport in the small intestine. The protein is associated with basolateral transport of Ca2+ in enterocytes. It was demonstrated that it binds both Pb and Ca2+ with a similar affinity [14]. Small intestinal absorption may be also facilitated by vitamin D. Large doses of the vitamin are not associated with significant increase of lead absorption, because of low vitamin D receptors saturation in the small intestinal epithelium. (On the other hand, lead inhibits vitamin D conversion into its active forms) [3]. Poor diet increases the risk of lead toxicity, with exposure remaining at the same level. Calcium deficiency increases lead accumulation, and thus its toxicity. Low dietary iron supply has a similar effect. There are studies indicating increased lead toxicity in children and pregnant women with iron deficiency. The deficiency leads to RBC production abnormalities and inferior thrive. Zinc deficiency causes increased lead absorption, which increases zinc elimination with urine, that closes the vicious circle. Calcium, iron and zinc deficiency correlated with chronic lead intoxication occurs mostly in groups of people of lower socio-economic status [13]. Absorbed lead occurs in the organism in two pools: a fast-exchange one (blood, soft tissues) - causing acute effects; and a low-exchange one (bones) metabolically inactive. In blood vessels lead is associated mostly with RBCs (75%), and the remaining part, associated with albumins, is transported throughout the organism and gradually penetrates organs: brain, kidneys, muscles and heart [1]. Genotoxic effect of lead: Generating intercellular reactive oxygen species, lead causes genomic damages in form of breaks of a single or double DNA strand, formation of DNA-DNA or DNA-protein crosslinks, or transversion of nitrogen bases. Damaged DNA generates chromatin structure abnormalities, associated with disruption of processes of repair, replication and transcription. That leads to formation of micronuclei, chromosome aberrations, and increased exchange of sister chromatids. Damaged DNA plays a significant role in pathophysiology of numerous diseases, including atherosclerosis, neurodegenerative disorders and ageing [15]. OBJECTIVE Among heavy metals, lead and mercury are most common elements in human environment, and therefore they most often cause some toxic effects. Their effects are neuro- and nephro-toxic, and lead to chronic disability. A high presence of methylmercury in aquatic ecosystems may lead to massive intoxication. The aim of this paper is to present the effects of chronic effects of lead and mercury on human organism Neurotoxic and neuropsychological effect of lead The mechanism of neurotoxicity: The neurotoxic effect of lead may take place with various mechanisms. Directly, lead may disturb the morphology of the central nervous system during the prenatal and infantile phases (disorders of neuron migration and differentiation), lead to premature differentiation of glial cells and disorder synapse formation. It may also cause an indirect reduction of sialic acid levels. Pharmacological effect of lead is a results of the fact that the element behaves as a pharmacological agent in the CNS. It is mostly a substitute of calcium, and - to some lesser 167 HEALTH AND WELLNESS 1/2015 Wellness and health extent - causes disturbance of neurotransmission – GABA-ergic and dopaminergic. In cells, lead disrupts calcium release in mitochondria, which leads to formation of free oxygen radicals activating the process of apoptosis. The indirect effect of lead on the CNS is based on disruption of other essential processes, including: thyroid hormone production, vitamin D3 metabolism, as well by induction of premature delivery [13]. The effect on children and cognitive functions. Considering higher susceptibility of paediatric organisms to the toxic effect of lead, and children's behaviour different than that of adults, children are at high risk of neurotoxic lead influence. In 1991, reacting to evidence of destructive lead effect on cognitive development, the Center for Disease Control and Prevention (CDC) and the World Health Organisation (WHO) reduced the admissible blood lead level from 25 μg/dL to 10 μg/dL [Polish Psychiatry]. The level of 10 µg/dL is considered toxic. However, there is evidence of a significant clinical effect of levels below 10 ng/dL, particularly in children. Tang et al. studied the effect of lead on the serotonergic system in infants and found abnormal, reduced levels of serotonin metabolites, dopamine and homovanillin acid already at the blood lead concentration of 2.5-7.5 ng/dL. That would suggest, that a long-term exposure - probably occurring already at the prenatal stage - has a neurotoxic effect on infantile brain. The effect may cause delayed psychomotor development and lower intelligence level at later stages of life. And the effect on glutaminaergic transmission responsible for neuronal plasticity may cause memory and learning disorders, as well as behavioural problems, including ADHD. Lead has also an effect on developing dopamine neurons. The element has a concentration-dependent effect on extracellular dopamine level. High lead concentrations cause a significant dopamine reduction, while low levels of the element lead to high concentrations of the hormone [7]. For that reason, it is currently agreed that there is no minimum lead level in children's blood that would have no effect on neurobehavioural disorders [16]. Studies completed in the USA demonstrated a correlation between the increased blood lead level in babies and infants and future anti-social, aggressive behaviour. A higher tendency for felony was found in those groups [16]. In Polish studies, abnormal family relations were more common in case of children with increased lead level, as well as increased nervousness and socialising difficulties. Children with higher lead levels performed inferior with observance of norms and principles in their family life, which had led to their behavioural disorders. Surkan et al. demonstrated that higher lead level was associated with poor results of neuropsychological tests and school achievements. The authors demonstrated also existence of an association between the lead level and inferior intelligence and visual-spatial assessment, as well as leadership abilities. A long-term exposure to lead causes some significant developmental consequences, behavioural disorders, reduce IQ, reduced tolerance of frustrating situations, hyperactivity and poor control over their reactions [18]. The effect of lead on the heart and circulation: By activation of free radicals and an effect on red-ox processes in the human organism, lead has a potential atherogenic effect. (disorders of the metabolism of fatty acids, increased lipid peroxidation causing an increased platelet adhesion and aggregation.) [1]. Lead has also a direct effect on 168 Mirosław Jasiński, Marcin Bryczek, Matylda Opolska, Ewa Zienkiewicz, Magda Chrościńska-Krawczyk, Ewa Jasińska Chronic effect of lead and mercury on human organism myocradium, causing oxidative stress which in turn disrupts function of the sympathetic system, reduces bio-receptor susceptibility and tone of the vagus nerve, and disrupts conductivity in the parasympathetic system. Those effects lead to the heart rhythm disorders – ventricular arrhythmia and myocardial infarction [8]. MERCURY Distribution in the natural environment: Mercury occurs in various forms in the natural environment. Those forms are: liquid metallic, highly volatile atmospheric, easily water soluble salts and hardly water soluble salts. Considering the ease of changing forms, the element may be carried to long distances (circulation of mercury). Natural sources of mercury are: volcanic eruptions, underwater exhalations, evaporation of lands and oceans, and erosion of mercury-containing rocks. Mercury present in the natural environment and originating from those sources is a common background. Values exceeding the background are considered harmful [5] Mercury emissions caused by humans The following are significant sources of mercury: paper industry, chlorine and sodium processing, pharmacological industry, production of gas discharge lamps, nonferrous metal foundries and improperly secured landfills. Large amounts of mercury are introduced to the atmosphere with burning coal, and 60-70- % of mercury compounds is present in the form of sulphur compounds - most commonly pyrite. Cement industry and oil refineries, as well as asphalt and tar producing plants have a significant mercury-polluting effect. In the past farmers used to use mercury salts to prevent mycotic diseases of grains, which resulted in high level of the element in the soil. Those dealings have been forbidden [5]. Mercury introduced by industry to the natural environment does not transform into harmless forms and constitutes a permanent pollution [2]. The level of 0.02 mg/m3 is considered the highest safe one. Pollutions get to soil and water, where they are transformed into organic mercury compounds. Those are much more toxic for humans compared to inorganic ones. In soil, mercury is transformed by bacteria and fungi. Processes of mercury methylation are important. They are completed by microorganisms, mostly by Pseudomonas spp. Only methylated forms of mercury are bio-available for plants [2]. Individual mercury forms may be inter-transformed by benthic microorganisms - mostly by sulphate-reducing, mathanogenic bacteria. Methylcobalamine is a donor of methyl groups, and the process is not catalysed by enzymes. In aerobic conditions the process of methylation is carried out with participation of enzymes and homocysteine, and methionine is a donor of methyl groups. Resulting methylmercury is easily absorbed by human organisms. Organic mercury compounds are introduced to ecosystems, predominantly aquatic ones. As a result, fish and seafood become a direct source of pollution for humans. Mercury is accumulated in trophic chains of aquatic organisms. Therefore fish and seafood are principal source of the compound for humans. Among fish species, fish of prey loca169 HEALTH AND WELLNESS 1/2015 Wellness and health ted at the top of a food-chain, demonstrate the highest levels of methylmercury. Besides the location in the ecosystem, also the dwelling place is of importance - benthic species demonstrate higher levels of methylmercury. Mercury accumulation in aquatic organisms is also determined by physical conditions of water, mostly by its temperature. Water temperature rise by 10oC leads to methymercury accumulation increase by 3%-5% [12]. Methylmercury accumulates mostly in fish muscular tissue, as a combination with cysteine. Those compounds have biochemical and molecular resemblance to methionine, therefore they are able to penetrate the blood-brain barrier, as well as the placenta and breast milk. Organic mercury compounds are very easily absorbed from the gastrointestinal tract. 95% of absorbed compounds are organic ones and approx. 7% are inorganic ones. Human organism absorbs mostly alkyl mercury compounds, including methylmercury. Humans are able to absorb those compounds also through the skin and the respiratory tract [2]. The effect of mercury on human organism: Chronic mercury intoxication causes mostly a neurotoxic and nephrotoxic effects, as well as affects the cardiovascular system and endocrine glands. Neurotoxic effect of mercury: Upon penetration of the central nervous system, mercury disturbs its architecture and activates degenerative processes. The morphological reconstruction involves axon degeneration and increased number of dendrites, most probably as a compensatory process. Inflammation develops, associated with increased level of pro-inflammatory cytokines. Similarly to lead, mercury triggers oxidative stress and increases the amount of reactive oxygen species, which leads to lipid peroxidation. Also processes of calcium metabolism and GABAergic conductivity are disturbed. That leads to impairment of neurotransmission. Endothelium dysfunction leads to reduced blood flow in cerebral and cerebellar vessels, and increased level of amyloid precursor proteins [2]. Mercury exposure has a particularly toxic effect on the developing foetal brain. The element causes reduction of number of neurons and their abnormal structure. The ability for microtubule organisation - important for the development of the central nervous system - is inhibited. Microtubule integrity is very important for the correct development of the nervous system, including cellular proliferation, development of cerebral and cerebellar cortex, extension and stabilisation of neurons and axodendritic transport. Interference of the compound with microtubules was a cause of neuropathological changes in brains of premature infants born in Iraq in 1971-72, exposed to the influence in utero at early stages of pregnancy. Mercury toxicity increases with deficiency of calcium that stabilises cellular membranes and some enzymes. On the other hand, excess of calcium ions causes necrosis and apoptosis of cells in the nervous system. Already at low concentrations, methylmercury leads to the increase of intracellular calcium ion levels in the cerebellar tissue, and its consequential degeneration [11]. No neurotoxic effect of amalgam as dental filling material was demonstrated. Also, no neurotoxic effect of thiomersal - a vaccine preservative - was demonstrated. That is a result of different toxicological properties. Thiomersal is an ethyl mercury derivative demonstrating strong bactericidal and fungicidal properties, used as a preservative in vaccines, preventing from their microbial contamination – currently it is present in just one vaccine available in Poland and designed for childre unde the age 170 Mirosław Jasiński, Marcin Bryczek, Matylda Opolska, Ewa Zienkiewicz, Magda Chrościńska-Krawczyk, Ewa Jasińska Chronic effect of lead and mercury on human organism of 1 year: the whole-cellular vaccine against diphtheria, tetanus and pertussis (DTP from Biomed Kraków [the dose of 50 µg thiomersal, or 25 µg of ethylmercury]). Ethylmercury is not harmful because, contrary to methylmercury, it is eliminated from the organism, and not accumulated. Ethylmercury elimination occurs mostly with faeces [9]. Nephrotoxic effect of mercury: Because of mercury elimination with urine, kidneys are organs demonstrating the highest accumulation level of the element. Nephron damage is a result of activation of free radicals and disturbed permeability of cellular membranes. The level of free radicals increases with inhibition of antioxidatives and the increasing effect of the oxidative stress resulting from dysfunction of mitochondria. Mercury causes also an increase of the intracellular calcium level, activating apoptosis. Also the sodium-potassium pump is affected, which results in accumulation of sodium, cellular oedema and eventual dysfunction. In clinical terms, mercury damage of kidneys is manifested mostly by increased protein elimination, with resulting reduction of the total protein and albumin levels. That may induce the development of membranous nephropathy [2]. CONCLUSIONS Damaged, under the influence of lead and oxidative stress, DNA play an important role in the pathophysiology of many diseases, among others: atherosclerosis, cancer, neurodegenerative diseases and the aging process. Directly influence the morphology of lead can impair the central nervous system in the prenatal period and infancy. Longterm exposure to lead causes significant consequences not pro-development, behavioural problems such as lowered IQ, reduced tolerance frustrating situation, hyperactivity and poor control over their own reactions. Chronic mercury poisoning causes mainly a result of neurotoxic and nephrotoxic and also affects the cardiovascular system and the endocrine glands, it causes abnormal architecture of activated degenerative processes. Mercury poisoning causes clinically kidney damage, resulting mainly increased urinary protein, and thus a reduction protein in total and albumin. REFERENCES 1. Boguszewska A., Pasternak K.: Ołów – wpływ na procesy biochemiczne w organizmie ludzkim. ANNALES Universitatis Mariae Curie- Skłodowska Lublin– Polonia. Vol .LIX, Supl. XI, 35 Sectio D 2004 2. Cyran M.: Wpływ środowiskowego narażenia na rtęć na funkcjonowanie organizmu człowieka. 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Umińska R.: Ocena poziomu pierwiastków śladowych stanowiących potencjalne zagrożenie dla zdrowia w glebach Polski narażonych na zanieczyszczenie. [Doctor's thesis]. Instytut Medycyny Wsi, Lublin 1988. 20. WHO, Regional Office for Europe: Air Quality Guidelines for Europe WHO Regional publications, European Series. 12 370 23 1987 STRESZCZENIE Ołów i rtęć są metalami ciężkimi najbardziej rozpowszechnionymi w środowisku człowieka. Najważniejsza wydaje się być kumulacja rtęci i ołowiu w ekosystemach. Szeroko rozpowszechnione spożycie ryb i owoców morza niesie za sobą zwiększone niebezpieczeństwo przewlekłego zatrucia metylortęcią, wynikające właśnie z kumulacji jej w tkankach ryb. Ołów i rtęć oddziałują toksyczni głównie na centralny układ nerwowy, układ krążenia oraz nerki prowadząc do przewlekłego nieprawidłowego funkcjonowania tych organów głównie w mechanizmie zwiększonego stresu oksydacyjnego.. NA czoło wysuwa się neurotoksyczność tych metali gdyż prowadzi do zaburzeń rozwoju centralnego układu nerwowego, nieprawidłowego rozwoju psychoruchowego, zaburzeń behawioralnych oraz zachowań antyspołecznych. ABSTRACT Lead and mercury are heavy metals present in the natural environment. Accumulation of mercury and lead seem to be of the higher importance. Common consumption of fish and seafood is associated with increased risk of chronic intoxication with methylmercury, being a result of accumulation of the substance in fish tissues. Lead and mercury have a toxic effect on the central nervous system, the cardiovascular system and kidneys, leading to chronic dysfunction of those organs, mostly according to the mechanism of the increased oxidative stress. Neurotoxic effect of those metals seems to be most important, as it leads to disorders of the central nervous system, improper psychomotor development, behavioural disorders and anti-social behaviour. 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