Heavy Metals Acting as Endocrine Disrupters

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Georgescu B. et. al./Scientific Papers: Animal Science and Biotechnologies, 2011, 44 (2)is associated with increased disease risksincluding bladder, lung, skin and other cancers.Moreover, pilot data suggest diabetogenic,neurological and reproductive effects, likewise.Increased health risks may occur at levels as lowas 10-50 ppb, while biological effects have beenobserved in experimental animal and cell culturesystems at much lower levels.Arsen is the first metal to be linked with endocrinedisruption through binding to the glucocorticoidreceptor and interfering with glucocorticoidhormones activity in several biological processes.In fact, instead of activating the glucocorticoidreceptor, as for example organochlorine pesticidesdo after binding to the estrogen receptor, As ratherinhibits glucocorticoid receptor-mediated geneactivation. In a similar manner, this metalinterferes with the estrogen receptor. Experimentshave shown that As markedly suppressed estrogenreceptor-dependent gene transcription of the 17ßestradiol-induciblevitellogenin gene in chickenembryo liver [2]. In cell cultures, non-cytotoxicconcentrations of As of 2-225 ppb significantlyinhibited estradiol receptor-regulated effects inhuman breast cancer MCF-7 cells [2].3. Cadmium (Cd)The main sources of contamination with Cd arerepresented by industrial aerosols, water wastesfrom extraction mines, phosphate-based fertilizers,Cd-containing pesticides etc. It has beendocumented that in the industrial area, Cdconcentration in the air peaks to 0.03 mg Cd/ m 3 .Fodder plants are the main constituents throughwhich Cd enters the food chain. It was shown thatCd levels in fodder may attain on average 0.6ppm. Moreover, through the process ofbioaccumulation, it reaches even higher concentrationsin animal products and subproducts.Interestingly, the accumulation process is agedependent,due to the long half-time of the metals,with up to 20 years needed for Cd to becompletely metabolized in human. Significantlyhigher Cd concentrations were demonstrated inmales compared to females, in various tissues andorgans such as liver, kidney, muscle, blood, hairand wool. A particular high affinity is describedfor the kidney cortex and the testes. Milk levels ofCd are about 2-10 mcg/l, however, they increaseabout tenfold in cases of abnormal exposure. Themetal is excreted in feces and urine but also milkand bile. The free fraction is rapidly metabolized,whereas the protein-bound fraction accumulatesfor years as a metaloprotein (metallothionein).Metallothioneins are cysteine-rich, low-molecularweight proteins, that have the capacity to bindvarious heavy metals (selenium, zinc, copper,cadmium, mercury, arsen, nickel, silver) throughthe thiol group of their cysteine residue. However,it appears that the formation of metallothioneinshas no impact on heavy metals toxicity.International guidelines restrict Cd concentrationto 1 mg/l water. By Romanian guidelines, theselevels are 0,01 ppm for milk, salted fish and oils;0.05 ppm for cheese, meat and meat products;0.03 ppm for vegetables. Despite its presence invery low concentrations in water, Cd mayaccumulate in the phytoplancton and enter theaquatic trophic chain, thus bioaccumulating inmolluscs, crustaceans and fish.Several data indicate that even low-level exposureto Cd interferes with the activity of steroidhormones in both male and female reproductiveorgans. Cd disrupts steroidogenesis by interferingwith the biosynthesis of androgens, estrogens andprogesterone in vivo and in vitro experiments,thus, leading to disturbed sex differentiation andaltered gametogenesis. On the other hand, it maybind both the estrogen and androgen receptor. Inutero animal exposure to Cd induces histologicalchanges in the breast linked with breast cancer [3,4]. Recently, a Lithuanian study brought evidenceof significantly higher Cd levels in breast tissueand biological media from women with breastcancer compared to controls, thus, suggesting thatexposure to Cd could be interpreted as a potentialrisk factor for breast cancer [5].4. Mercury (Hg)Organic mercury fungicides are widely used inagriculture. In addition, mercury is used as acatalyser in industrial processes. In the form ofaerosols it is largely spread in the environment.Mercury polluted water forms sediments furthermetabolized by microorganisms into methylmercury,which is a stable but highly neurotoxicand teratogenic compound. Some organic mercuryderivates accumulate in plants by absorption fromsoil and water through the plants roots. Forexample, use of organic mercury fungicides inagriculture resulted in contamination of potatoestubercles reaching a concentration of 0.03-0.2ppm mercury. A direct correlation was foundbetween the Hg content in fodder and the90
Georgescu B. et. al./Scientific Papers: Animal Science and Biotechnologies, 2011, 44 (2)concentration of the heavy metal in tissuesoriginating from foddered animals. Animals maybe contaminated by water and fodder supply,through the skin, by inhalation of vapors andaerosols, or transplacental. Mercury compoundsare transported by blood and the lymph anddiffuse in practically all tissues but arepreferentially stored in the liver, kidney, spleen,skeleton, lymph nodes, brain and the muscles. Inpatients with chronic intoxication, mercury exertsneurotoxic, teratogenic, mutagenic and endocrinedisruptingeffects. It is metabolized and excretedthrough milk, feces, kidneys and saliva.Completely, mercury is eliminated after minimum90 days post-exposure. Previous reports indicatedthat both organic and inorganic mercurycompounds highly accumulate not only in the liverand the kidneys but also in major endocrineglands, for example, the hypothalamus, thepituitary gland, the thyroid, the testes, the ovariesand the adrenal cortex. Mercury-based compoundsdisrupt steroidogenesis, including sex hormonessynthesis, male and female fertility as well as thehypothalamic-pituitary-thyroid axis and thehypothalamic-pituitary-adrenal axis [6]. Most dataavailable indicate the fact that mercury may act asa major endocrine disrupter [7, 8].5. Nickel (Ni)The heavy metal nickel originates from naturaland artificial sources and can be found inpractically all environmental compartments: air,water, soil and living organisms. In the air it isdistributed in the form of aerosols that containvarious nickel concentrations, depending on theprimary source of metal contamination. Transportationand distribution of Ni particles betweendifferent compartments of the environment isstrongly dependent on the particles size and theclimatic conditions. Generally, the particlesoriginating from artificial resources are smallercompared to those derived from natural sources.Water contamination results by sedimentation ofmetal particles form the atmosphere, of residualindustrial waste and city waste as well as byerosion of the soil and natural rocks. In runningwater, Ni is mainly transported in precipitatedform; in lakes, it is found in ionic form,predominantly in association with organic matter.Part of Ni compounds may reach by the way ofrunning surface waters the planetary ocean. Theamount of these compounds plunged yearly intowater is estimated around 135 x 10 7 kg. Accordingto the type of the soil it contaminates, Ni showsdiverse mobility, eventually reachinggroundwater. Acid rain shows great ability tomobilize Ni from soil. The amount of metal that isabsorbed by particles from soil depends on thephysical and chemical properties of the soil,including the type of the soil, the pH, the soilhumidity and the organic matter content of thesoil. Terrestrial plants absorb the metal from soil,mainly by their roots and Ni levels above 50mg/kg dried substance are toxic for most plants.High Ni levels were reported for aquatic plants. Inunpolluted waters, Ni levels in fish may varybetween 0.02-2 mg/kg. Nevertheless, these valuesmay increase about tenfold in fish fromcontaminated water. Nickel concentrationscommonly found in the air vary between 5-35ng/m 3 , with a 0.1-0.7 μg daily humancontamination. Drinking water contains less than10 μg/l Ni, whereas its concentration in fresh foodis less than 0.5 mg/kg product. Soy, some driedvegetables, nuts and oat may contain highquantities of the metal. The daily Ni intake fromfood largely varies, in dependence of food habits,between 100-800 μg/day with a medium intake of100-300 μg/day. Pulmonary contamination isabout 2-23 μg/day. Nickel may be asorbed byrespiration, ingestion or transdermal. The mostfrequent way of contamination is the respiratoryway, whereas gastro-intestinal contamination is ofsecondary relevance. Transdermal absorption isneglijible. The absorption rate is related to thecompound solubility; as carbonyl, Ni is mostrapidly and completely absorbed in animals andhuman. It circulates bound to albumin. Thedigestive absorption rate is highly variable anddependent on diet composition. In human, theabsorption percent from water is about 27% incontrast to the absorption percent from food whichis less than 1%. All body secretions representpotential pathways for Ni excretion, includingurine, and bila, sweat, tears and milk. UnabsorbedNi is excreted through the feces. Nickel chloridecontamination by ingestion or inhalationdecreased iodine uptake by the thyroid gland.Given orally (0.5-5.0 mg/kg per day, for 2-4weeks) or by inhalation (0.05-0.5 mg/m 3 ) to rats,nickel chloride significantly decreases iodineuptake by the thyroid, the effect being morepronounced with inhaled Ni.91
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