Research Progress on Heavy Metals Detoxification in Human Body

Hui ZHANG,Jianxia SUN,Mingwei LI,Cuijuan ZHU,Yunfeng HU,Shi WU,Rui JIAO,Weibin BAI,

1.China Rural Technology Development Center,Beijing 100045,China;

2.Faculty of Chemical Engineering and Light Industry,Guangdong University of Technology,Guangzhou 510006,China;

3.Department of Food Science and Engineering,Jinan University,Guangzhou 510632,China

Responsible editor:Na LI Responsible proofreader:Xiaoyan WU

Generally existing in nature in natural density widely,heavy metals mainly get access to human body through air,water,soil and food and other ways.With the development of industry,human activities on the mining,smelting,processing and commercial production of heavy metals become increasingly more,and the wide application of heavy metals make the heavy metal pollution become more and more serious.Heavy metals are listed as the priority pollutant in the countries all over the world,indicating that environmental heavy metal pollution has become a major worldwide environmental problem.Heavy metals in the natural environment cannot be degraded,and can be enriched through food chain.The heavy metals of low concentration in the natural environment can be accumulated in great amount in human body through the concentration of food chain,which can destroy the normal physiological metabolism in human body and do great harm to human health.Therefore,how to detoxify the heavy metals in human body has become a focal point for human attention and research.Since artificial chelating agents have some side effects,the protein,enzyme,food and other new detoxification ways which have no side effects in the detoxification of heavy metals provide us with new ideas.Many studies have found that food contains dietary fiber,tea polyphenols and minerals can inhibit the adsorption of heavy metals,and Se and Zn can resist lead and cadmium.Based on the summary of related analysis and research,we stated these detoxification ways to provide references for further study.

Harm of Heavy Metals

Heavy metals refer to the metals with the density of greater than 4.5kg/cm3,such as gold (Au),silver (Ag),mercury (Hg),copper (Cu),lead (Pb),cadmium (Cd),chromium (Cr),and some of the heavy metals can get access to human body through food,which will disturb the normal physiological function in human body and do harm to human health,known as toxic heavy metals.Such kinds of metals mainly include Mercury(Hg),cadmium(Cd),chromium (Cr),lead (Pb),arsenic (As),zinc (Zn),tin (Sn).Arsenic is a non metallic element,but according to its chemical properties and in view of its toxicity,it is generally listed as a toxic heavy metal element.According to harm to human body,these heavy metal elements are classified into medium toxicity (Cu,Sn,Zn)and the strong toxic elements(Hg,As,CD,Pb,Cr).There are 5 kinds of heavy metals doing great harm to human body:Pb,Hg,Cr,Sn and Cd.Through the biological concentration of food chain,the concentration of heavy metals could increase by thousands of hundreds of times,and finally enter into human body.The toxicity of the heavy metals entered into human body will become obvious after a period of time of accumulation,which may make people hard to become aware of,making it possess great potential harm.It is believed that the harm of heavy metals to living body is caused by the combination of heavy metals with biomacromolecule.Heavy metals can combine with the active centre of enzyme or the sulfydryl of active proteins,leading to the conformational change of proteins and loss of enzymatic activity,and therefore interfering with the normal physiology and metabolism of cells.In addition,heavy metals can also generate free radical through the redox reaction in human body,which can do oxidative damage to cells,possessing great toxicity.

Pollution and harm of cadmium

All chemical forms of cadmium are toxic to humans and animals.Because cadmium compounds are mostly soluble in water,it can be absorbed into the body through digestive tract and respiratory tract,which can act with the organ system in the whole body,but cannot enter into the fetus and breast milk.Excessive amounts of cadmium can cause kidney,lung,liver,liver,bone,reproductive effects and cancer.The International Agency for Cancer Research (IARC) has classified cadmium into the first category of human carcinogens.The effects of cadmium on the immune system are mostly behaved as immune suppression,and it has a certain correlation with the exposure pathway,dose,time and other factors.Cadmium has obvious toxic effect on the reproductive system of mammals.It can cause ovarian pathological changes,resulting in follicular development disorder; it can interfere with ovulation and fertilization process,causing temporary infertility.Moreover,it can also cause a variety of cardiovascular system disorders,kidney function damage,bone mineral density decrease and so on.

Pollution and harm of mercury

Mercury is relatively scarce in the earth’s crust,and only a very few mercury exists in nature in simple substance status,making it the only liquid metal which has mobility.Cinnabar(HgS),chlorine sulfur mercury mine,livingstonite and other minerals connected with HgS re the most common minerals.Mercury having wide application,the content of Mercury in air,water and soil has increased by 3 times since the industrial revolution,even higher nearby the industrial park,greatly polluting human living environment.After Mercury in the natural environment scattering into the water,it can accumulate in the aquatic animals through food chain,and seriously pollute the fishery products.For example,due to the pollution of mercury-containing wastewater in the Songhua River of China,the Mercury content in the collected fish samples is 0.74 mg/kg on average,and the highest is 3.24 mg/kg,which is 10 times higher than the permissible amount stand in fish in China.Aquatic plants and animals have strong enrichment capacity of Mercury.Although the content of Mercury in sea water is very low,the fish body can contain a great amount of Mercury through accumulation,mostly organic Mercury.People eating 0.1 g of Mercury will be poisoned to death.The toxicity of mercury and its compounds is great,especially the organic compounds of mercury.Methyl mercury is the most toxic,the effect of which on human is particularly stubborn,and after entering human body,it will spread all over human body,which mainly attacks the nervous system,especially central nervous system,of which the most serious is the two hemispheres of the cerebellum and brain,and the damage is not reversible.Methyl mercury can also pass through the placenta barrier to make inroads on fetus,making the fetus with congenital mercury poisoning,which will be deformity,or dementia.In addition,methyl mercury can inhibit the formation of sperm cells,which makes the male fertility decline.Inorganic mercury compounds are also toxic to the human body,and inorganic mercury compounds can be absorbed into human body through the gastrointestinal tract,for example,the major performance of mercuric chloride,inorganic mercury poisoning is the digestive and kidney damage.

Pollution and harm of lead

Lead is widely distributed in nature.About 40%lead around the world is used in the manufacture of storage batteries,20%added to gasoline as an anti explosive agent in the form of alkyl lead,12% for building materials,6%for the cable outer protective layer,5%to manufacture ammunition,and the remaining 17% for other purposes.Only about 1/4 of lead is recycled,and the most of the rest lead is discharged into the environment in the forms of exhaust gas,waste water and waste residue,resulting in lead pollution in large area in the environment of air,water and soil,which finally does great harm to human health,especially great to children.In the development countries,there are about 15-18 million of children suffer from brain damage caused by lead poisoning.Lead in low concentration can result in learning and memory function barrier.The rat poisoned by lead has kidney damage and lipid peroxidation,and long-time low lead contamination can cause lead poisoning myocardial damage,which can also damage the functions of adrenal cortex,thyroid and prepituitary gland,as well as the reproductive system.

At present,heavy metals,especially cadmium,mercury and lead,have greatly polluted the natural environment,and are hard to get natural clearance,which brings serious harm to human health.Therefore,the study on the decontamination and restoration of heavy metal pollution is of great significance to restore the ecological environment and care human health.

Methods for Detoxification of Heavy Metals in Human Body

In recent years,great achievements have been made in the physiological and molecular mechanisms of the adsorption,accumulation and translocation metal ions of heavy metals,especially the study related with the chelation of heavy metals are most thorough.It has been found that the chelation of metal ion complexing agents like organic acid,amino acid,metal translocator and metallothionein to heavy metal ions can buffer buffer cytoplasmic concentration of metal ions,increase the solubility,and therefore increasing the resistance of animals to heavy metals as well as the their transport efficiency in human body to different degrees,which could achieve the detoxification.Meanwhile,some new ways could also detoxify heavy metals in human body.

Chelation of heavy metals by metallothionein

Metallothionein (MT),chemical name known as metal sulfur histidine trimethylammonium inner salt,is a kind of metal combining protein which is widely existed in creatures with low molecular weight(2-7 kD),rich in cysteine (20%-30%),with no histidine and aromatic amino acids.Because of high sulfydryl content,it has great affinity to heavy metals,and therefore it has chelation effects on many kinds of heavy metals such as the positive ions of Cu,Zn,Pb,Ag,Hg and Cd.At low pH environment,MTs could remove metals.MT can be induced by metals,cytokines,hormones,cytotoxic drugs,organic chemicals,and stress.The study has found that MT evolution is highly conserved,including four isoforms of MT-I and MT-II,MT-III and MT-IV,of which MT-I and MT-II are widely existed in the visceral organs of most mammals,mainly in liver and kidney cells,and they also involved with their function adjustment.MT-III is mainly distributed in the central nervous system,mainly distributed in astrocytes (especially in the cell bodies and processes),followed by neuronal cells,and it is also reported that there is a small amount distributed in the germ cells,small intestine,stomach,kidney and olfactory cortex cells.MTIV is mainly distributed in the keratinocytes and stratified squamous epithelium cells of skin,tongue,gastrointestinal tract and other organs.Its binding metal capacity is in the order of Hg2+＞Ag+＞Cu2+＞Cd2+＞Zn+,and once it combined with Cd2+or Ag+,it is hard to replace Cd2+and Ag+with other metals,but the metals can still be removed.There have been many reports related with the detoxification of MT to heavy metals.For example,the MT generated by the induction of Cdin testis can resist the damage of Cd.XIN et al.MT could improve the sperm density and vialbility of the infertile males with blood lead concentration of greater than 70 μg/L to different degree(P ＜0.05).Moreover,Amiard et al.found that the concentration of metal sulfide in mussels increased with the increase of the concentration of Pb2+,and the metallothionein had a high ability to chelate metal,which could reduce the damage of Pb2+.Shao et al.[22]found that the Anabaena transformed by a-KKS-a (metal sulfur protein mutant gene) had strong resistance to heavy metals.Currently,it is still unclear about the detoxification mechanism of MT,which might through the following 3 ways:first,chelate with heavy metals to form inactive compounds; second,chelate with heavy metals and discharge out of body; third,reduce the permissible amount of metal.At present,the most convinced opinion is that MT could combine with the metal ions through sulfydryl and then reformulated Cys-M or Cys-M-Cys bonds in reducing condition.Under oxidizing condition,the cleavage of Cys-M(M)bond could release metals and form Cys-Cys bond,and then achieve the removal of metals.Park et al.found that the detoxification capability of MT to some heavy metals is in the order of Cd＞Zn ＞Cu ＞Pb ＞MT ＞Fe ＞Ag,but it had no effect on Pb and Fe.One of the advantage of MT is that different from other proteins,it could resist enzymatic hydrolysis,and will not be hydrolyzed into a single amino acid by enzyme,which can be absorbed in a complete form in the gastrointestinal tract.

Detoxification of lead by apple polyphenols

Polyphenol apple(AP)is a general term for the phenolic compounds in apple.It is reported that AP has many physiological functions such as antioxidant,anti cancer cell proliferation,regulating lipid metabolism and so on.WANG et al.believed that the tannic molecules in acorn powder contained many ortho phenolic hydroxyl groups,which can be used as the multidentate ligand to combine with the lead ion to from precipitate,performing obvious effects on reducing blood lead and increasing urinary excretion of lead.GAO et al.believed that tea had the significant performance of tea on reducing blood lead and urinary lead was related with the highlight performance of adsorption ions in tea.Many studies have proved that the oxidative damage mediated by active oxygen stress involves in the pathological process of lead poisoning,and antioxidant may play an important role in the treatment of lead poisoning.PU et al.believed that tea catechin had the ability of radicals scavenging and complex metal ions,which can block and reverse the cells following oxidative injury induced by lead,and they also noticed that tea polyphenol(TP)could reduce the lead content in liver significantly.VC and chrysanthemum also could reduce oxidative damage and promote lead discharge[7].

The antioxidant activity of AP is higher than that of tea polyphenols,and there are more concentrated tannins in AP.The test results of AI et al.[4]showed that it may be the antioxygenation of AP that block the pathological process of lead poisoning,and some elements in AP chelate and deposit the lead ions.With significant ability in lead discharge,AP substances can promote the discharge of urinary lead,resist the absorption of blood lead caused by metal lead,reduce blood lead level,and reduce the accumulation of metal lead in thighbone and liver.The health food of AP is effective in inhibiting the absorption of lead by human body,which can discharge the lead poison,reduce the damage effects of lead poison on human body,providing new ideas and ways for the application of AP in controlling lead poisoning.However,further study is required on the improvement of physical conditions of human body after using AP in lead poisoning and action mechanism of AP and lead in human body.

Detoxification by seaweed dietary fiber

YANG et al.[2]studied the adsorption effect of dietary fibers from seaweeds on Cd2+,Pb2+and Hg2+by simulating the environment of stomach and small intestine in vitro,and feeding rat in vivo,and found that the dietary fibers from seaweeds played an important role in preventing and reducing the accumulation of heavy metal poisons in human body.The adsorption effect of dietary fibers on heavy metal was higher in small intestine than that in stomach.Among the four seaweeds,the adsorption ability of Laminaria japonica was the best,followed by Eucheuma,wheat bran,Gracilaria and Sargassum.The adsorption effect of four seaweeds fiber on Pb2+was the best,but the worst on Hg2+.The scavenging ability of dietarty fibers was in the order of Eucheuma ＞Laminaria japonica ＞wheat bran ＞Gracilaria ＞Sargassum,indicating that dietary fibers from the four seaweeds had the adsorption ability on heavy metals.And the mechanism was as follows:

The adsorption effect of dietary fibers on heavy metals include physical adsorption and chemical adsorption.The dietary fibers from seaweeds have porous structure and large specific surface area,equipped with the ability of physical adsorption.Other studies have proved that the adsorption of dietary fibers on heavy metals accorded with the Langmuir adsorption rule,belonging to monolayer adsorption[8].According to the surface properties of the material,the effect of pH on physical adsorption is not significant,but it has significant effect on chemical adsorption.Physical adsorption relies on the carboxyl and uronic acid combined with the pphenolic acid and amino acid of dietary fibers from seaweeds.The analysis related with infrared spectroscopy showed that the carboxy group of the dietary fibers participated in the bonding interaction during the formation of adsorbate from dietary fibers and minerals,while hydroxyl and amino did not perform bonding effect,indicating that carboxyl played the man role in the adsorption of dietary fibers on heavy metals in dietary fires structure.The dissociation status of these carboxy groups had significant effects on the adsorption of dietary fibers on heavy metals that when pH value increased,there would be more protonic dissociation from carboxy groups,which could increase the adsorption amount of heavy metals,vise versa.Therefore,the adsorption effect of dietary fibers on heavy metal was higher in small intestine than that in stomach.In addition,the heavy metal ions can also compete with the proton for the carboxyl sites,and the amount of carboxyl sites of the two was also related with the dissociation constant and relative concentration of the two.The binding capacity of dietary fibers to heavy metals was related with the type of heavy metals.The adsorption of seaweeds dietary fibers on heavy metal ions was selective.It found that the adsorption effect of four seaweeds fibers on Pb2+was the best,but the worst on Hg2+,which was mainly because that the dietary fibers from seaweeds can absorb the metal ions with large polarizability selectively,which played an important role in removing the harmful metal ions in human body and avoiding the loss of beneficial microelement.The binding capacity of dietary fibers to heavy metals was also related with the type of dietary fiber.Different kinds of seaweed dietary fibers had different adsorption effects and in vivo scavenging ability on the three kinds of heavy metals.But from an overall point of view,Eucheuma and Laminaria japonica showed strong scavenging ability,which was mainly related to their own structures,such as the differences in number and nature of the active groups like uronic acids,phenolic acids and amino acids.It may also subject to the activity of cations of these active groups and the elements of the bonded organic substituent groups,like the difficulty level of cation exchange and steric-hinerance effect can also affect the adsorption effect.The effects of dietary fibers from seaweeds on scavenging heavy metals were also affected by the physiological environment of animals.Large intestine was the place for dietary fiber hydrolization,and was also an important part for the adsorption of salt and water.Therefore,the scavenging ability on the heavy metal ions in vitro cannot be determined by the scavenging status in vivo,which should also considered the possibility that the dietary fibers bonded with heavy metal ions can be affected by the glycolysis of entric microorganisms and release some heavy metal ions.

Experiments showed that the adsorption effects of dietary fibers from Laminaria japonica was stronger in vitro adsorption tests,while the scavenging effects of Eucheuma dietary fiber was the best in vivo adsorption tests,which may because dietary fibers bonded with heavy metal ions can be affected by the glycolysis of entric microorganisms and release some heavy metal ions.Therefore,the scavenging ability of dietary fibers from seaweeds in vivo depended on the comprehensive results of the adsorption of dietary fibers on heavy metal ions and the glycolysis of entric microorganisms.

Detoxification of glutathione S-transferase

Glutathione S-transferase (GST,EC2.5.1.18) is a group of multifunctional protein widely distributed in various types of biological cells,and as the major phase II detoxification enzyme,it participate in the process of detoxification of exogenous or endogenous toxin.GST can catalyze the bonding of various hydrophobic or electroactive compounds and reduced glutathione(GSH),the bonding product of which would be isolated in the vacuoles of plant or be transported to the apoplast,so as to realize the goal of detoxification.In addition,the activity of GSH dependent peroxidase of GST can remove hydroperoxide,and the isomerase activity involved in tyrosine degradation,while non-catalytic carrier activity involved in the binding and transport of anthocyanin.In addition,GST could participate in stress information transduction,cell apoptosis and developmental regulation control.GST involving in the detoxification of heavy metals mainly through the following 2 ways:GST can directly catalyze the bonding of GSH with heavy metals from ionic covalent,so as to reduce the toxicity of heavy metal ions and promote the transport of heavy metal to vacuoles or apoplast;the peroxidase activity of GST can onset ucleophilic attack to hydrogen peroxide by using GSH to make it reduce into monohydroxy alcohol with low toxicity,so as to alleviate the oxidative stress generated from heavy metal stress[10].We can also get GST from food or vegetables to achieve detoxification effect.

Glutathione S-transferases (GSTs) is a superfamily composed of two homologous subunits.First,it can catalyze the binding of some endogenous and foreign harmful substances with reduced glutathione (GSH) in the body,which can bind various hydrophobic compounds like drugs and carcinogens with GSH into the substances that are easy to discharge,so as to protect important nucleophile like proteins and nucleic acids.Second,it can be used as the binding protein to bind and transport various hydrophobic compounds,such as hormones,drugs,carcinogens and other using its high affinity[11].Third,it has the activity glutathione peroxidase,which can prevent lipid peroxidation damage.GSTs is ubiquitous in mammals,birds,insects,fish,aquatic invertebrates,plants and microorganisms,and the contents of GSTs are relatively high in the placenta and liver of mammals.GSTs and other antioxidant enzymes can remove active oxygen together in the cell to protect cells from oxidative damage.CYP2E1 is a subtype of cytochrome P-450,an ethanol inducible enzyme,and CYP2E1 can reduce molecular oxygen to generate reactive oxygen species(ROS)and initiate lipid peroxidation process.According to the report of MariM,ithe HepG2 cells with CYP2E1 overexpression could increase the content of reduced glutathione,and induce the expression of a-type as well as particle size of GST and catalase,which can protect the short-term oxidative stress[12].GSH is a kind of molecular scavengers composed of glutamic acid,glycine and cysteine,which is not only the major non-protein sulphydryl compounds in the tissue,but also the essential substrate for glutathione peroxidase(GSH-Px) and glutathione S-transferase (GSTs) to decompose hydrogen peroxide,and the ratio of reduced glutathione (GSH) and oxidized glutathione (GSSG) can be used as an index of lipid oxidative damage.GSTs develop its antioxidant activity through transporting sulfydryl among molecular,and thus it can repair the function of large molecules with oxidative damage such as DNA,proteins,which is a strong evidence for the detoxification of heavy metals.

Detoxification of cadium by marine green algae

The unique cell wall composition and structure of green algae,as well as the resistance to the cadmium induced toxicity of selenium and zinc have a positive effect on the prevention and intervention removal of cadmium poisoning.The mechanism for the cadmium discharge is as follows:

Adsorption to remove cadmiumThe adsorptive property of algae to heavy metals is mainly determined by the composition and structure of its cell wall[13].The cell wall of green algae is in net structure mainly composed of polysaccharide,protein,cellulose and lipids,with a certain negative charge,and has a large surface area and viscosity.Among these components,-OH,-COOH,-NH,-NH,-SH and other groups can bind with cadmium ion to make a large number of Cd2+adsorbed on the cell wall.The binding mode is usually one or several functions of complexation,chelation,ion exchange,physical adsorption,redox and precipitation.In the process,the cadmium ion and the biological material act quickly,and complexing and ion exchange are the major ways.The complexation is generated from the binding of metal ions and the negatively charged functional group in biological ligands,and carboxyl has strong complexation ability; the functional groups involved in ion exchange process mainly include a large amount of carboxyl and sulfuric acid groups in green algae,and others such as thiol and amino groups may also have some adsorption function[14].The thick cell wall of green algae is made of cellulose containing fibers,which can form a micro porous network structure,making it beneficial to the full contact of these functional groups with metal ions.

Active transport to remove cadmiumActive transport is an intracellular absorption related with metabolic process which required the participation of energy and certain specific enzymes,and it is a specific bio-concentration pathway for living organism that the various generated metallorganics(like metalloprotein) can effectively concentrate the trace elements of low concentration.Green algae transfer the harmful cadmium ions into harmless cd-binding proteins by inducing the production of MT to restrict the existence of free cadmium ions[15].Through the synergistic effect of the above mechanisms,the heavy metal making it unable to be absorbed until discharged from the body.

Toxin immunity of selenium and zinc to cadmiumSelenium(Se)can effectively eliminate the damage of cadmium to body in many ways to reduce the accumulation of cadmium in human body.Currently,it is still unclear about the mechanism of the toxin immunity of selenium to cadmium,but there have been the following understandings:first,the antioxygenation of selenium; second,the capacity of selenium to remove the cadmium induced oxygen radicals; third,the generation of selenium-cadmium compounds in vivo[16]; fourth,the synthesis of MT induced by selenium in vivo.Based on the resistance of selenium to cadmium,there are studies on supplement of selenium to the cadmium burden level of residents,the results of which showed that the biological application of selenium could promote the discharging of toxic cadmium,making it another evidence for the resistance of selenium to cadmium.

Zinc (Zn) can induce the intestine produce more MT to combine the cadmium taken by mouth,which is the main reason why zinc could resist the toxicity of cadmium[17].Laboratory results suggest that in response to the supplement of zinc under cadmium exposure,it can reduce the cadmium burden of the body by reducing cadmium adsorption in intestinal tract.On the other hand,insufficient dietary zinc could improve the cadmium adsorption in intestinal tract and storage of cadmium in human body.It suggests that it can change suggests that he metabolism of cadmium and its toxic side effects in vivo by adjusting zinc intake.MT plays an important role in the process of cadmium detoxification.Although further study is still required for some of its mechanisms,the above theoretical analysis and fact argumentation shows that taking green algae is conductive to the heavy metal cadmium discharging,and sufficient or high uptake amount of selenium and zinc from everyday diet can not only maintain their biological functions in human body,but also play an important role in the everyday life of the people living around the cadmium polluted area.

Other detoxification ways

The anthocyanin in plants is a wide-known bio-flavonoids existed in waxberry and grape,and its major physiological functions are free radical scavenging and antioxidant capacity.Study has shown that anthocyanins are the most effective antioxidants up to now,and one of the most potent free radical scavenger,the antioxidant property of which is 50 times higher than VE and 20 times higher than VC[18].These functions are able to inhibit the damage of heavy metals,and the consumption of fruits containing anthocyanins can effectively remove heavy metals.As the detoxification mechanism of anthocyanins is still not clear,further research is needed.

It is reported that water spinach contains significant amounts of dietary fibers,minerals,carotenoids,chlorophyll,vitamins and essential amino acids,which can remove heavy metals.Its leaves and stems also have the capacity to inhibit arsenic,cadmium,lead,and play an important role in metabolism as the affiliative metallothionein.Water spinach also contains various minerals,like K,iron,sodium,and calcium,which can compete with heavy metals and inhibit the combination of heavy metals with intestinal protein receptors[19].The uptake of water spinach is of great help for the removal of heavy metals in the human body,but the inhibition mechanism remains to be studied.

As for the chelation treatment,a chelating agent treatment strategy coupled with sugar and amino acids was put forward,including the removal of N-glucose-N-dithio carboxylic acidamino acid in cadmium poisoning[20],removing five hydroxyl cyclohexyl amino acid in lead and cadmium poisoning,removing N-(1-dexodize-D-βfructose-1-yl)-L-amino acid in lead and cadmium poisoning[21],removing N-(α-L-arabinose furanose-1-yl)L-cystenine in lead poinsing,removing five hydroxyl cyclohexyl amino acid in platinosis poisoning.In view of the drawback of the previous study,attention wasfocused on using endogenous molecules or green molecules like sugar and amino acids as the building block to construct new low or non-toxic chelating molecules by fully applying HSAB theory,such as sugar amine chelating molecules,which constructed green chelating agent.The advantages of these novel chelating agents including:first,high of tissue specificity;second,unique biliary excretion pathway; third,causing no redistribution of toxic metals to the brain and bone; fourth,complexing no trace metal elements in vivo.These new chelating agents are of great significance to develop safe,efficient,and suitable long-term oral administration of heavy metal.

Conclusion and Prospect

Agreat many studies have been carried out on the harm of heavy metals to human bodies and the ways for human to detoxify the heavy metals in vivo.Although we have introduced some detoxification substances in this paper,apart from the molecular mechanism of metallothionein in chelation,some of the detoxification mechanisms of heavy metals are still not clear,and great differences still exist even to the existed results.In addition,it remains to be solved as how to extract these substances and put into food and health.New way is still needed on the road to explore the detoxification of heavy metals.

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