TOXIC EFFECT OF HEAVY METALS

TOXIC EFFECT OF HEAVY METALS

BY

ZAINAB FAROK JIBRIL

MARCH, 2018
ABSTRACT
          Heavy metal are generally referred to as those metal which posses a specific density of more 5gkm2 and adversely affect the environment and living organisms. The most commonly found heavy metal in waste water include arsenic, cadmium, chromium e.t.c. which risks for human health and environment and they also enter surrounding by natural means and through human activities. This research was conducted to investigate the toxic effect of heavy metals. Arsenic is none of the most important heavy metals causing disquiet from both ecological and individual health. Lead is a highly toxic metal whose widespread use has caused extensive environmental contamination and health problems in many parts of the word. Mercury adversely affects the marine environment. Cadmium is the deventh toxic heavy metal as per ATSDR ranking. It is a by-product of zinc production which humans or animals may get exposed to at work or in the environment. Once this metal gets absorbed by humans, it will accumulate inside the body through life.       







INTRODUCTION
Metal are substances with high electrical conductivity, malleability and luster, which voluntarily lose their electrons to form cations, metals are found naturally in the earth’s crust and their composition vary among different localities, resulting in spatial variations of surrounding concentrations. The metal distribution in the atmosphere is monitored by the properties of the given metal land various environment factors (Khlifi and Hamza, 2010). The main objective of this review is to provide insight into the sources of heavy metals and their harmful effect on the environment and living organisms. Heavy metals are generally referred density of more than 5gkm3 and adversely affect the environment and living organisms (Jarup, 2003). These metals are quintessential to maintain various biochemical and physiological functions in living organisms when in very low concentrations, however they become noxious when they exceed certain there should concentrations. Although it is acknowledged that heavy metals have many adverse health effects and last for a long period of time, heavy metal exposure contimues and is increasing in manu parts of the world. Heavy metals are significant environmental pollutants and their toxicity is a problem of increasing significance for ecological, involuntary, nutritional and environmental reasons (Jaishankar et al., 2013; Nagajyoti et al., 2010). The most commonly found heavy metals in waste water include arsenic, cadium, chromium, copper, lead, nickel and zink, all of which cause risks for human health and the environment (Lambert et al., 2000). Heavy metals enter the surroundings by natural weathering of the earth’s crush mining, industrial effluents, urban runoff, sewage discharge, insect or disease control agents applied to crops and many others (Moraise et al., 2012). Figure 1 show the global production and consumption of selected toxic metal during 1850-1990 (adapted from Nriagu, 1996).
          The global production and consumption of selected toxic metals during 1850-1990 (adapted from Nriagu, 1996).
          Although these metal have crucial biological functions in plants and animals, sometimes their chemical coordination and oxidation-reduction properties have given them an additional benefit so that they can escape control mechanisms such as homeostasis, transport, compart metallization and binding to required cell constituents. These metals bind with protein sites which are made for them by displacing original metals from their natural binding sites causing malfunctioning of cells and ultimately toxicity. Previous research has found that oxidative deterioration of biological macromolecular is primarily due to binding of heavy metals to the DNA and nuclear protein (flora et al., 2008).
Heavy metals and their toxicity mechanisms
Arsenic
Arsenic is one of the most important heavy metal causing disquiet from both the ecological and individual health stand points [hughes et al 1988]. It has a semimetallic property, is prominently toxic and carcinogenic and is extensively available in the form of oxides or sulfides or as a salt of iron, sodium, calcium, copper, etc. (singh et al., 2007). Asentic is the twentieth most abundant element on earth and its inorganic forms such as arsenite and arsenate compounds are lethdl to the environment and living creatures. Human may encounter arsenic by natural means, industrial sources of from unintended sources. Drinking water may be containes by use of arsenical pesticides, natural miniral deposits or in appropriate disposal of arsenical chemicals. Deliberate consumption of arsenic in case of suicidal attempts or accidental consumption by children may also result in cases of acute poisoning (Manzumder, 2008; saha et al., 1999). Arsenic is a protophydryl group of cells causing mal functioning the sulphydryl group of cells causing mal functioning of cell respiration, enzymes and mitosis (Garden and Quastel, 1948).
Mechanism of arsenie toxicity

In arsenic biotrans formation, harmful in organic arsenic biotra, algae, fungi and humans to give monomethylarsonic acid (MMA) and dimethy larsimi acid (DMA). In this biotransformation process, these inorganic arsenic species (IAS) are converted enzymetically to methy lated arsenicals which are the end metabolites and the biomarker of chronic arsenic exposure.
iAs (V) à iAs (iii) à MMA (V) à DMA (V)
          biomethylation is a detoxification process and end products are methylated inorganic arsenic such as MMA (V) and DMA  (V) is not excreted and remains inside the cell as an intermediate and remains inside the cell as an intermediate product.
Monomethylarsenic acid (MMA iii), an inter mediate product is found to be highly toxic compared to other arsenicals, potentially accountable for arsenic induced carcinogenesis (singh et al., 2007).
LEAD
          Lead is a hihly toxic metal whose widespread use has cause extensive environmental contamination and health problems in many parts of the world. Lead is a bright silvery metal, slightly blush in a dry atmosphere. It begins to tarnish on contact with air, thereby forming a complex mixture of compounds, depending on the given conditions. Figure 2 shows various sources of led pollution in the environment (Sharma and ubey 2005). The sources of lead exposure include mainly industrial processes, food and smoking, drinking water and demostic sources. The sources of lead were gasoline and house paint which has been extended to lead bullets, plumbing pitcher, storage batteries, toys, and faucets (Thurmer et al., 2002). In the US, more than 100 to 200, 000 tons of lead per year is being released  from vehicle exhausts some is taken up by plants, fixation to soil and flow into water bodies, hence human exposure of lead in the general population is either due to food or drinking water (Goyer, 1990). Lead is an extremely toxic heavy metal that disturbs various plant physiological processes and unlike other metals, such as Zinc, copper and manganese, ir does not play any biological functions. A plant with high lead concentration fastens the production of reactive oxygen species (ROS), causing tipid memberance damage that ultimately leads to damage of chlorophyll and photosynthetic processes and suppresses the overall growth of the plant (Najeeb et al., 2014). Some research revealed that lead is capable of inhibiting the growth of tea plant by reducing biomass and debases the tea quality by changing the quality of its components (young sheng et al., 2011). Even at low concentrations, lead treatment was found to cause huge instability in ion uptatke by plants, which in turn leads to significant metabolic changes in photosynthetic capacity and ultimately in a strong inhibition of plant growth (Mostafa et al., 2012).

















Various pollution in the environmental (Adapted from sharama and Dubey, 2015).
Mechanisms of lead toxicity
          Lead metal causes toxicity in living cells by following ionic mechanism and that oxidatioive stress. Many researchers have shown that oxidative stress in living cells is caused by the imbalance between the production of free radicals and the generation of antioxidants to detoxify the reactive intermidiates of to repair the resulting damage. Figure 3 shows the attack of heavy metals on a cell and the balance between ROS production and the subsequent defense presented by antioxidants. Antioxidants as e.g glatathing, present in the cell protect it from free redicals such as H2O2 under the influence of lead, however, of antioxidabts decreases. Since glutathione exists both in reduced (GSH) and oxidized (G S S G) state, the reduced form of glutathione gives Its reducing equivalents (h++e-) from its thiol groups of cystein to ROS in order to make them stable. In the presence of the enzyme glutathrome peroxidase, reduced glutathione readily binds with another molecule of glutathione after donating the election and forms glutathione disulfide (GSSG). The reduced form (GSH) of glutathione accounts for 90% of the total glutathione content and the oxidezed form (GSSG) accounts for 10% under normal additionas. Yet under the condition of oxidative stress, the concentration of GSSG ezcellds the concentration of GSH. Another biomarker for oxidative stress in lipid peroxidation, since the free radicals collects electron from lipid molecules present inside the cell membrane, which eventually cause lipid peroxidation (wadhwa et al., 2012; flora et al., 2012). At very high concentration ROS may cause structural damage to cells, proteins, nucleis acid, membrance and lipids, resulting in a stressed situation at cellular level (Mathew et al., 2011
Figure 3
The attack of heavy metals on a cell and the balance between ROS production and the subsequent defense presented by antioxidants.
The ionic mechanism of lead toxicity occurs mainly due to the ability of lead metal ions to replace other bivalent cations like ca2+, mg2+ fe2+ and monovalent cations Na2+, which ultimately disturbs the biological metabolism of the cell. The ionic mechanism of lead toxicity causes significant changes in various biological processes such as cell adhension, intra and inter-cellular signaling, protein folding, maturation, apoptosis, ionic transportation, enzyme regulation, and release of neurotransmitters. Lead can substitute calcium even in picomolar concentration affecting protein kinase C, which regulates neural excitation and memory storage (flora et al., 2012).
Mercury
The metallic mercury is a naturally occurring metal which is a shiny silver-white, odorless liquid and becomes colorless and odorless gas when heated. Mercury is a very toxic and exceedingly bio accumulative. Its presence adversely affects the marine environment and hence many studies are directed towards the distribution of mercury pollution include anthropogenic activities such as agriculture, municipal waste water discharges, mining, incineration, and discharges of industrial waste water (chen et al. 2012).
Mercury exists mainly in three forms: metallic elements, inorganic salts and organic compounds, each of which possesses different toxicity are present widdly in water resources such as lakes, rivers and oceans where they are taken up by the microorganisms and get transformed into methyl mercury within the microorganism, eventually undergoing bio magnification casing significant disturbance to aquatic lives. Consumption of this contaminated equatic animal is the major route of human exposure to methyl mercury (transande et al., 2005). Mercury is extensively used in thermometers, barometers, pyrometers, hydrometers, mercury are lamps, fluorescent lamps and as a catalyst. It is also being used in pulp and paper industries as a component of batteries and in dental.
Figure 4
          The global usage of mercury for various applications (total in 2005: 3,760 metric tons). Mechanism of mercury toxicity
          Mercury is well known as a hazardous metal and its toxicity is a common cause of acute heavy metal poisoning with cases of 3,596 in 1997 by the American Association, of poison control centers. Methyl mercury is a neurotoxic compound which is responsible for micro tubule destruction, mitochondrial damage, lipid peroxidation and accumulation of neurotoxic molecules such as serotonin, aspartate and glutamate (Patrick 2002). The total amount of mercury emission into the environment has been assessed at 2,200 metric tons annually (ferrara et al., 2000). It is estimated that 8 to 10% of American women have merury levels that would induce neuro logical disorders in any child they gave birth to, according to the both the environment protection agency and national academy of science (haley, 2006). Animal which are exposed to toxic mercury have shown adverse neurological and behavioral changes. Rabbits when exposed to 28.8mg/m3 mercury vapor for 1 to 13 weeks have shown vague pathological changes, marked cellular degeneration and brain necrosis (Ashe et al. , 1953).
          The brain remains the target organ for mercury, yet it can impair any organ and lead to mal functioning of nerves, kidneys and muscles. It can interrupt with intracellular calcium homeo stasis. Mercury binds to freely available thiols as the stability constants are high (Patrick, 2002). Mercury vapors can cause bronchitis, asthma and temporary respiratory problems. Mercury plays a key role in damaging the tertiary and quaternary protein structure and alfers the cellular function by attaching to the selenohydryl and sulfhy dry groups which undergo reaction with methyl mercury and hamper the cellular structure. It also intervenes with the process of transcription and translation resulting in the disappearance of ribosomes and eradication of endoplasmic reticulum and the activity of natural killer cells. The cellular integrity is also affected causing free radical formation. The basis for heavy metal chelation is that even though the mercury sulfhy dryl bond is stable and divided to surrounding sulfhy dryl consisting ligands, it also contributes free sulfhy dryl groups to promote metal mobility within the ligands (bern hoft, 2011).
Cadmium
          Cadmium is the seventh most toxic heavy metal as per ATSDR ranking. It is a byproduct of zinc production which humans or animals may get exposed to at work or in the environment. Once this metal gets absorbed by humans, it will accumulate inside the body throughout life. This metal was first used in World War 1 as a substitute for tin and in paint industries as a pigment. In today’s scenario, it is also being used in rechargeable batteries, for special alloys production and also present in tobacco smoke. About three fourths of cadmium is used in alkaline batteries as an electrode component, the remaining part is used in coatings, pigment and plantings and as a plastic stabilizer. Human may get exposed to this metal primarily by inhalation and ingestion and can suffer from acute and chronic in toxications. Cadmium distributed in the environment will remain in soils and sediment for several decades. Plants gradually take up these metals which get accumulated in them and concentrate along the food chain, reaching ultimately the human body. In the US, more than 500,000 workers get exposed to toxic cadmium each year as per the agency for toxic substance and diss=ease registry (Bernard, 2008, mutlu et l. , 2012). Researchers have shown that in china the total area polluted by cadmium is more than 11,000 hectares and its annual amount of industrial waste of cadmium discharged into the environment is assessed to be more than 680 tons. In japan and china, environment cadmium exposure is comparatively higher than in any other country (Han et al., 2009). Cadmium is predominanthly found in fruit and vegetables due to its high rate of soil-to-plant aransfer (satarug et al., 2011). Cadmium is a highly toxic non essential heavy metal that is well recognized for its adverse influence on the enzymatic systems of cells, oxidative stress and for inducing nutritional deficiency in plants (Irfan et al., 2013)
Mechanism of cadmium toxicity
          The mechanism of cadmium toxicity is not under stood clearly but their effects on cells are known (patrrick, 2003). Cadmium concentration increases 3,000 fold when it binds to cystein- rich protein such as me tallothionein. In the liver, the cystein-matallothionein complex causes hepa to toxicity and then it circulates to the kidney and gets acculated in the renal tissue causing nephro toxicity. Cadmium has the capability to bind with cystein, glutamate, his tidine and aspartate ligands and can lead to the deficiency of iron (castag netto et al., 2002). Cadmium and Zinc have the same oxidation and hence can replace zinc present in metallo thionein, there by inhibiting it from acting as a free radical scavenger within the cell.









Conclusion
          The toxic effects of heavy metals affect the environment and living organisms (jarup, 2003). Heavy metals are significant environmental pollutants and their toxicity is a problems of increasing significant for ecological, evolutionary, nutritional and environment reasons (jaishankar et al., 2013; nagajyti et al., 2010). Most of the commonly heavy metals are found waste water include arsenic cadmium, chromium, copper, lead, nickel and zinc, all of which cause risks for human health and the environment (lambert et al., 2000) various sources at heavy metals include soil erosion, natural weathering of the earth’s crust, mining, industrial effluents, urbanrun off, sewage discharge, insect or disease control agent applied to crops and many others (morals et al., 2012).











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