Arsenic And Fluoride Two Major Ground Water Pollutants-PDF Free Download

Arsenic and fluoride Two major ground water pollutants

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Vol. 48, July 2010, pp. 666-678 Review Article Arsenic and fluoride: Two major ground water pollutants Swapnila Chouhan & S J S Flora* Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior 474 002, India Increasing human activities have modified the global cycle of heavy metals, non metals and ...

arsenic and fluoride along with the recent updates of to cancer in kidney liver lungs urinary bladder and
their combined exposure to better understand the joint skin10 Trivalent arsenicals including sodium arsenite
action of these two toxicants and the more soluble arsenic trioxide inhibit many
enzymes by reacting with biological ligands which
Arsenic posses available sulfur groups Symptoms of acute
Arsenic is 33rd element in the periodic table arsenic intoxication usually occur within 30 min of
It exists in the metallic state in nature in exposure Severe nausea and vomiting colicky
three allotropic forms and in several ionic forms abdominal pain and profuse diarrhoea bloody in
Environmental arsenic exists mainly as sulphide some cases due to vasodilation with transudation of
complexes e g realgar As2S2 orpiment As2S3 and fluid into the bowel lumen and sloughing leading to
iron pyrites Arsenic is the 20th most abundant increased peristalsis11 12 The clinical features of acute
element in the earth crust known as a poison and arsenic poisoning include gastrointestinal discomfort
human carcinogen Arsenic is listed as the highest nausea diarrhea and abdominal pain haemolysis
priority contaminant on the ATSDR EPA priority list central and peripheral nervous system disorders
of hazardous substances at Superfund sites5 In India headaches weakness delirium and cardiovascular
many areas from West Bengal have shown to be disorders hypertension shock Major effects of
affected whereas Bihar is an emerging area with acute arsenic exposure in humans include haemolytic
high arsenic contamination6 The possible methods anaemia hemoglobinuria and jaundice that lead to
of exposure to arsenic are contact ingestion and renal failure Chronic exposure to inorganic arsenic is
inhalation Ingestion of contaminated drinking associated with irritation of the skin and mucous
water is the predominant source of significant membranes dermatitis conjunctivitis pharyngitis
environmental exposure globally and rhinitis Bowen s disease is a long term
Absorbed arsenic passes to bloodstream and complication of chronic arsenic Chronic exposure
distributed to organs tissues after first passing through also results in fatigue and loss of energy
the liver Once absorbed arsenic rapidly combines inflammation of the stomach and intestines kidney
with the globin portion of haemoglobin and therefore degeneration cirrhosis of the liver bone marrow
localises in the blood within 24 h Arsenic degeneration and severe dermatitis Death from acute
redistributes itself to the liver kidney spleen lung arsenic poisoning is usually caused by irreversible
and gastrointestinal tract with lesser accumulation in circulatory insufficiency Chronic toxicity is much
muscle and nervous tissue7 9 After accumulation of more insidious and the diagnosis is often difficult to
small dose of arsenic it undergoes methylation establish
mainly in the liver to monomethylarsonic acid and
dimethylarsinic acid which are excreted along with
residual inorganic arsenic in the urine Biologically
the trivalent arsenite is significantly more active than
the pentavalent arsenate including the ability to
induce gene amplification in mammalian cells
Arsenate and arsenite have different fates in the body
Arsenate enters the cell via the phosphate carrier
system It can bind to polyphosphates like adenosine
di phoshate after that it is rapidly hydrolyzed
Arsenite can bind to thiols such as glutathione GSH
and thiol containing proteins Arsenic is cleared from
the body relatively rapidly and primarily through
kidney Urine is the primary route of elimination for
both pentavalent and trivalent inorganic arsenicals
Major routes of exposure and various steps in the
metabolism of arsenic is described in Fig 1
Toxicity Exposure to inorganic arsenic causes
many adverse human health effects including Fig 1 Major routes of exposure and various steps in the
cardiovascular hepatic and renal diseases in addition metabolism of arsenic
Mechanism of toxicity Trivalent inorganic ROS reactive nitrogen species RNS also are
arsenite As 3 acts as thought to be directly involved in oxidative
React with molecules containing sulfhydryl damage to lipids proteins and DNA in cells exposed
groups such as glutathione GSH to arsenic Many recent studies have provided
aminolevulinic acid dehydratase ALAD etc experimental evidence that arsenic induced
and form strong complex with vicinal thiols generation of free radicals can cause cell damage
groups thereby inhibiting the activity of and death through activation of oxidative sensitive
molecules signalling pathways17 These ROS and RNS
are capable of damaging a wide variety of
Inhibits PDH activity perhaps by binding to
cellular macromolecules including DNA lipids
the lipoic acid moiety
and proteins Finally cellular signal transduction
Methylated trivalent arsenicals such as MMAIII can be altered e g activation of transcription
are potent inhibitors of GSH reductase and factors changes of gene expression cell growth
thioredoxin reductase proliferation and differentiation can be promoted
Blocks the Krebs cycle and interrupt oxidative and apoptosis leading to cell death or cancer
phosphorylation resulting in a marked development can be induced18
depletion of cellular ATP and eventually death ROS may result in strand breakage nucleic acid
of the metabolising cell protein crosslinking and nucleic base modification
Base modification crosslinking of DNA DNA and
Pentavalent inorganic arsenate acts as DNA proteins sister chromatid exchange and single
Undergoes reduction to form arsenite AsIII or double strand breakage may lead to the disruption
Mimic phosphate in in vivo system there by of transcription translation and DNA replication19
can replace phosphate in the sodium pump Genotoxic effects caused by arsenic are implicated
and the anion exchange transport system in carcinogenic outcomes20 21 Recent studies have
Can form esters with glucose and proposed two mode of action for arsenic induced
gluconate forming glucose 6 arsenate and DNA damage i inhibition of various enzyme
6 arsenogluconate respectively These involved in DNA repair e g poly ADP ribose
compounds resemble glucose 6 phosphate polymerase I PARP I an important DNA repair
and 6 phosphogluconate thus inhibit activity enzyme22 and ii induction of ROS capable inflicting
of hexokinase DNA damage23
Uncouples in vitro oxidative phosphorylation
termed as arsenolysis
Many studies have focused on arsenic induced
toxicity via generation of reactive oxygen
and nitrogen species in biological systems13
Oxidative stress is a relatively new theory of
arsenic toxicity14 10 Arsenic and fluoride mediated
generation of reactive oxygen species involves
generation of superoxide O2 singlet oxygen
1O2 peroxyl radical ROO nitric oxide NO 15
Among these ROS hydroxyl radical is generally
assumed to be the critical species that directly
attacks DNA Fig 2
Dimethyl arsenic reacts with oxygen to
form dimethylarsenical radicals and superoxide
anoin This dimethylarsenical radical combine
with molecular oxygen and generates
dimethylarsenic peroxyl radical Hydroxyl radical
generates during this reaction then further Fig 2 Structure of some common chelating agents used against
involves in oxidative stress16 In addition to arsenic poisoning
Arsenic is a well known human carcinogen of these chelating agents however suffer from
that causes cancers in many human organs10 serious side effects Meso 2 3 dimercaptosuccinic
It is generally suggested that arsenic shares acid DMSA is found to be one of the least toxic
many properties with tumor promoters It acts by drugs that could be given orally However hydrophilic
inducing intracellular signal transduction activating and lipophobic properties of DMSA do not allow it to
transcription factors and changing the expression pass through cell membrane Recently some mono
of genes that are involved in promoting cell growth and diasters of DMSA especially the higher
proliferation and malignant transformation Research analogoues have been developed and tried against
shows that arsenic significantly affects specific cases of experimental arsenic poisoning in in vitro
signal transduction molecules that are involved and in vivo both28 29 MiADMSA is a monoester
in mediating cellular proliferation or apoptosis of DMSA with a straight and C 5 branched chain
including MAPKs p53 AP 1 and NF B These amyl group thereby increasing the lipophilicity and
changes in cellular signaling pathways have been number of carbon atoms of the compound Due to its
associated with both arsenic carcinogenicity10 The lipophilic nature it can easily cross the cell membrane
tumor suppressor gene p53 for example has been and chelate arsenic from intracellularly and
linked to the DNA damage cell cycle perturbations extracellularly both This is the best therapeutic part
and apoptosis that is seen with arsenic24 25 of this chelating agent It also assumed that
Treatment Chelating agents are organic MiADMSA could be able to decrease the oxidative
compounds capable of linking together metal ions to stress in tissue either by removing arsenic from the
form complex ring like structure called chelates target organs or by directly scavenging ROS through
Chelating agents have been used clinically as its sulfhydryl group Flora and Mehta30 have also
antidotes for acute and chronic arsenic poisoning reported that MiADMSA does not show any major
Chelators not only enhance excretion but also alternation in heme synthesis pathway except for a
decrease the clinical signs of toxicity by preventing slight rise in the zinc protoporphyrin levels that
metals from binding to cellular target molecules26 indicates mild anemia MiADMSA has been seen to
Chelator form a complex with the respective toxic ion be slightly more toxic in terms of copper and zinc loss
and these complexes reveal a lower toxicity and more and some biochemical variables in the hepatic tissue
easily eliminated from the body27 It includes 2 3 in females as compared to male rats31
dimercaprol British Anti Lewisite BAL sodium Apart from synthetic chemical chelators studies
2 3 dimercaptopropane 1 sulfonate DMPS meso have been carried out to explore natural antioxidants
2 3 dimerceptosuccinic acid DMSA Fig 3 Most against the toxic elements Antioxidants AOX are
substances which inhibit or delay oxidation of a
substrate Antioxidant molecules are thought to play a
crucial role in counteracting free radical induced
damage to macromolecules Nutritional antioxidants act
through different mechanisms 1 directly neutralize
free radicals 2 reduce the peroxide concentrations
and repair oxidized membranes and 3 quench iron to
decrease ROS production via lipid metabolism short
chain free fatty acids and cholesterol esters neutralize
ROS32 There is a wide range of antioxidants which
can counteract the condition of oxidative stress
It includes vitamins phenolic compounds flavonoids
carotenoids hormones melatonin estradiol and
insulin In addition minerals such as selenium zinc
manganese magnesium and copper are also involved
in hundreds of antioxidant roles in the body Apart
from the free radical scavenging property antioxidants
are known to regulate the expression of number of
Fig 3 Chemical structure of quercetin and silybin active genes and signal regulatory pathways and thereby may
component of silymarin group prevent the incidence of cell death33
Vitamin C ascorbic acid acts as a scavenger maintenance of hepatic protein synthesis via RNA
of free radicals and plays an important role in activation and preservation of mitochondrial transport
regeneration of vitamin E tocopherol It scavenges function57 62 Chemical structure of quercetin and
the aqueous reactive oxygen species ROS by rapid silymarin are shown in Fig 4
electron transfer that inhibits lipid peroxidation Flora et al 63 have studied herbal products extracts
Recent studies in rats using sodium arsenite however against several heavy metal toxicity Besides
indicate that vitamin C ameliorated arsenic induced providing beneficial effects in eliminating body
toxicity34 36 Effect of vitamin C and E on arsenic burden of arsenic and reversing the altered
induced oxidative damage and antioxidant status has biochemical variables these herbal products intake
been studied37 Co administration of vitamin C and E could also be useful in enhancing endogenous
to arsenic exposed rats resulted in a reduction in the antioxidant levels Flora et al63 have also reported
levels of lipid peroxidation protein carbonyls and moderate chelating and antioxidant properties of
hydrogen peroxide and an elevation in the levels Moringa oleifera Centella asiatica and Aloe vera
of reduced glutathione38 40 Vitamins have been against arsenic during concomitant administration64 66
known to alter the extent of DNA damage by reducing These naturally occurring herbal products known to
TNF level and inhibiting the activation of caspase possess an effective arsenic removal property either
cascade in arsenic intoxicated animals41 Our group individually or in combination for the treatment of
has also reported beneficial effects of vitamin E chronic arsenic toxicity67
supplementation during arsenic and fluoride There is also increased interest to find out a new
intoxication42 treatment strategies to minimize side effects and
Flavonoids such as quercetin hesperetin to achieve maximum beneficial effects Among
naringenin and epicatechin have been proposed to those strategies which are proposed some include
exert beneficial effects during cancer cardiovascular combination therapy co administration of structurally
disease and neurodegenerative disorders43 46 The different chelating agents supplementation of an
precise mechanisms by which flavonoids exert their antioxidant with chelating agent or co administration
beneficial remain unclear However recent studies
have speculated that their classical hydrogen donating
antioxidant activity is unlikely to be the sole
explanation for cellular effects47 49
Quercetin is one of the most frequently studied
dietary flavonoids and is ubiquitously present in
various vegetables fruits seeds nuts tea and red
wine It is an excellent free radical scavenging
antioxidant47 It has been shown to have very potent
antioxidant and cytoprotective effects in preventing
endothelial apoptosis caused by oxidants In addition
quercetin is a more potent antioxidant than other
antioxidant nutrients such as vitamin C E and
carotene on a molar basis50 53
Silymarin is also a polyphenolic antioxidant
flavonoid widely found in vegetable sources54 55 The
potential role of oxidative stress in pathogenesis
induced by arsenic suggests that antioxidants can be
considered as an alternative approach in mitigating
arsenic induced toxicity37 Silymarin has been proved
to be effective in restoring the diminished level
of antioxidants against arsenic induced toxicity in
in vitro56 The possible mechanism underlying the
protective properties of silymarin include prevention
of GSH depletion destruction of free radicals Fig 4 Combined toxicity of arsenic and fluoride
of antioxidants with moderate chelating abilities diffusion When ionic fluoride enters the acidic
beside antioxidant potential 67 68 Reports have environment of stomach lumen it is largely converted
indicated that treatment with chelating agents into hydrogen fluoride74 It is rapidly distributed by
alone may not provide better clinical recoveries69 the systemic circulation to the intracellular and
but combinational therapies with antioxidants extracellular sites of tissues However ion normally
like n nacetylcysteine27 lipoic acid70 captopril71 accumulates only in calcified tissues such as bone and
quercetin and also some herbal extracts72 have shown teeth In blood ion is asymmetrically distributed
considerable promise in improving clinical recoveries between plasma and blood cells so that the plasma
Our group have also reported that co administration concentration is approximately twice as high as that
of naturally occurring vitamins like vitamin E or associated with the cells75 Fluoride is distributed
vitamin C along with the administration of a from plasma to all tissues and organs In humans and
thiol chelator like DMSA or MiADMSA may be laboratory animals approximately 99 of the total
more beneficial in the restoring altered biochemical body burden of fluoride is retained in bones and teeth
variables Although it has only limited role with remaining distributed in highly vascularized soft
in depleting arsenic burden14 Mishra et al have also tissues and the blood Fluoride is concentrated to high
reported that combined administration of MiADMSA levels within the kidney tubules so this organ has a
with M oleifera provided better treatment than higher concentration than plasma76 78 Ingested
monotherapy with the thiol chelator in chronic arsenic fluoride that is not absorbed into the GI is excreted in
toxicity Studies strongly support the theory that the faeces Some fluoride is also lost from the body
combination therapy has a major role to play in future through sweat
approach towards finding a safe suitable and an
effective treatment for heavy metal poisoning72 Toxicity Fluoride predominantly effects the skeletal
systems teeth and also the structure and function
of skeletal muscle brain and spinal cord79 General
Fluoride symptoms of acute fluoride poisoning includes nausea
Fluorine is the 13th most abundant element on
salivation vomiting diarrhea and abdominal pain
earth It cannot exist outside a controlled
Fluoride is also found to be involved in the alteration
environment without combining with other of metabolism of some essential nutrients which leads
substances to become fluorides Three main to hyperkalemia hypocalcemia hypomagnesemia
anthropogenic sources were identified as fertilizers hypophosphatemia Persistent fluoride serum level
combusted coal and industrial waste with phosphate leads to mineral homeostasis which ultimately causes
fertilizer being the most significance source of cellular damage Symptoms of acute fluoride toxicity
fluoride73 There are ionizable and non ionizable have been summarized in Table 1
organic and inorganic fluorides Fluorine is probably Chronic fluoride toxicity occurs after the long term
an essential element for animals and humans ingestion of small amount of fluoride It inhibits
Low concentrations provide protection against the synthesis of DNA protein and inhibits cell
dental caries especially in children Minimum proliferation and cytotoxic at high doses76 80
concentration of fluoride in drinking water required Symptoms of long term fluoride toxicity include
to produce protective effects is approximately emaciation stiffness of joints and abnormal teeth and
0 5 mg L bones Other effects include lowered milk production
Soluble inorganic fluorides ingested through water and detrimental effects on reproduction Fluoride is
and foods are almost completely absorbed from the known to cross the blood brain barrier and accumulate
gastrointestinal GI tract by a process of simple in the brain of animals exposed to high fluoride
Table 1 Symptoms of acute fluoride poisoning
Gastric Symptoms Electrolyte abnormalities Neurological effects Cardiovascular effects
Hypersalivation Hypocalcemia Headache Widening of QRS
Nausea Hypomagnesemia Tremors Various arrhythmias
Vomiting Hyperkalemia Tetanic contractions Shock
Diarrohea Hypoglycemia Hyperactive reflexes Seizures Cardiac arrest
Abdominal pain Muscle weakness Muscular spasm
Mucosal injury
levels81 Recent studies have shown accumulation of damage or by directly diminishing the occurrence of
fluoride in the hippocampus of the brain causing oxidative damage by means of enzymatic SOD
degeneration of neurons decreased aerobic Catalase GPx GR and non enzymatic antioxidants
metabolism and altered free radical metabolism in GSH vitamins and several essential micronutrients
liver kidney and heart82 Long term exposure to Some studies have shown lipid peroxidation LPO as
fluoride through various fluoride containing water and one of the molecular mechanisms involved in chronic
other products leads to development of fluorosis fluoride induced toxicity86 It may impair a variety of
Fluorosis is also known as a crippling and painful intra and extra mitochondrial membrane transport
disease Fluorosis includes skeletal dental and systems that may contribute to apoptosis It leads to the
non skeletal fluorosis Dental fluorosis occurs during formation of secondary products such as conjugated
the period of enamel formation It is linked to excessive dienes hydrocarbon gases ethane and carbonyl
incorporation of fluoride into dental enamel and compounds malondialdehyde and decreased levels of
dentine which prevents normal maturation of enamel polyunsaturated fatty acid87 In addition to this ROS
Skeletal fluorosis is a pathological condition which reactive oxygen species is also found to play major
includes inhibition of bone hardening mineralization role during pathogenesis of fluoride It may directly
causing the bones to become brittle and their oxidize amino acids leading to a loss of function of
tensile strength may be reduced83 Symptoms include proteins and a deactivation of enzymes88
limited movement of joints skeletal deformities and A possible mechanism of DNA damage induced by
intense calcification of ligaments muscle wasting and fluoride is as follows i fluoride has a dense
neurological deficits76 84 negative charge and is biochemically very active thus
directly effect on DNA due to strong affinity for
Mechanism of toxicity Fluoride leads to toxicity uracil and amide bonds by NH F interactions89
as follows ii fluoride can combine stably with DNA by
Binds calcium ions and may lead to covalent bonding affecting the normal structure of
hypocalcemia which could further lead to DNA iii fluoride can induce the production of free
osteoid formation radicals which can damage DNA strands directly or
Disrupts oxidative phosphorylation glycolysis by lipid peroxidation initiated by free radicals90 and
coagulation and neurotransmission by binding iv fluoride may depress enzyme activity such as
calcium DNA polymerase which might further affect the
Inhibits Na K ATPase which may lead process of DNA replication or repair and thereby
to hyperkalemia by extracellular release of damage DNA91 However few studies have reported
potassium fluoride does not induce DNA damage while others
Inhibits acetyl cholinesterase which may be have observed the genotoxic potential of fluoride in
partly responsible for hyper salivation rats and human cells92 94 Effect of fluoride on DNA
vomiting and diarrhea cholinergic signs damage in lymphocytes and its possible relation with
oxidative stress needs extensive research
Exact mechanism of fluoride toxicity is not known
It has been suggested that oxidative stress can be a Fluoride was found to be an equivocal carcinogen
possible mechanism through which fluoride induces by the National Cancer Institute Toxicological
damage to the various tissues Due to high Program95 IARC evaluated that there is limited data
electronegativity fluoride F has a proclivity to form which provide inadequate evidence about fluoride
strong hydrogen bonds especially with OH and NH induced carcinogenicity In a recent study rats and
moieties in biomolecules Fig 4 Fluoride is also mice given sodium fluoride in drinking water at 11
able to exert powerful influences on various enzymes 45 or 79 mg L have shown only the incidence of
and endocrine gland functions that affect or control osteosarcomas in bones of male rats96
the status of oxidant antioxidant systems in living
organisms Hydroxyl radicals were previously Treatment There is no safe and effective
proposed as initiation of lipid peroxidation LPO treatment for the cases of chronic fluoride toxicity
through iron catalyzed Fenton reaction in However the treatment for acute poisoning
membranes85 The cell has several ways to alleviate mainly relies on the use of antioxidants vitamins
the effects of oxidative stress either by repairing the and essential elements Administration of some
vitamins like vitamin C and E is known to revert approach to manage the menace It is known that a
toxic effects induced by fluoride exposure42 The nutritionally rich diet may play an important role in
mechanism of action of vitamin C might be due to its alleviating fluoride intoxication It has been observed
powerful reducing action97 98 During fluoride toxicity that supplementation of adequate dietary factors
generated free radicals attack the double bonds of such as protein calcium magnesium melatonin and
polyunsaturated fatty acids initiating a chain reaction selenium may significantly reduce toxic effects of
and affect membrane integrity and cellular function fluoride in bone and other soft tissues106 107 These
This chain reaction is inhibited by vitamin E substances decrease the absorption of fluoride and
tocopherol by reacting with free radicals and increase its removal from the body In addition use of
converting itself into an tocopheroxyl radical which green leafy vegetables cumin seeds milk paneer
is not harmful99 This tocopheroxyl radical thus orange vegetable oil garlic ginger and pumpkin
formed is converted back to tocopherol by cytosolic must be promoted Aluminium promotes the urinary
vitamin C100 Thus vitamins C and E show synergistic excretion of fluoride calcium and phosphate interfere
action in the recovery of altered variables suggestive the gastrointestinal absorption of fluoride and borate
of oxidative stress and organ damage by fluoride enhances its eliminating process108
exposure98 In addition to this certain non vitamin
antioxidants such as Co enzyme Q Co Q and Co exposure to arsenic and fluoride
liponate have also been studied against fluoride Few reports are available in literature which
toxicity CoQ is present in cells in two forms suggest the effect of combined exposure to arsenic
oxygenated ubiquinone and a reduced form and fluoride on major organs Li et al109 have studied
ubiquinol Only the reduced form demonstrates anti effects of arsenic fluoride co exposure on rat teeth
oxidative properties It reduces the concentration of and concluded that no detectable amount of arsenic
MDA in rabbit blood plasma wherein it prevents the gets deposited in dentine and no combined effects of
initiation and propagation of peroxidation of arsenic and fluoride have been seen on dental tissues
polyunsaturated fatty acids lipids and phospholipids However some studies have also shown that
of mitochondrial membranes101 Grucka Mamczar combined exposure to arsenic and fluoride is related
et al 102 have studied the effect of some vitamin to distinct damage on the nerve system of the
vitamins A C and E and non vitamin antioxidants offspring with decreased learning and memory
Coenzyme Q and liponate on fluoride induced lipid ability110 Chinoy and Shah111 have reported altered
peroxidation and found that these antioxidants are histology of cerebral hemisphere following combined
most effective in counteracting the free radical arsenic fluoride exposure wherein the effects
processes generated by sodium fluoride produced by arsenic are more prominent as compared
Flavonoid like quercetin has also been studied to fluoride Genotoxic effects of combined exposure
against fluoride poisoning which support its beneficial to arsenic and fluoride have been reported to be
role on lipid peroxidation serum cholesterol more pronounced as compared to their individual
level triglycerides and total proteins in fluoride exposure100 112 Guizhou113 has suggested that the
intoxication103 Mixture of quercetin sulfonates has toxicological effects of fluoride can be enhanced by
been reported to stimulate and normalize tissue arsenic More contradictory results have been reported
respiratory activity and thus can be helpful for the in different experimental studies in which different
prevention of fluoride toxicity in persons who are joint actions such as independent synergistic and
exposed to excessive fluoride104 The antioxidative antagonistic effects have been observed108 114 116 This
action of quercetin is due to the presence of hydroxyl indicates that the interaction mechanism of these two
groups in B ring of the molecule Fig 4 which elements in relation to the development of endemic
contain two catechol or three pyrogallol hydroxyls disease is considerable complicated and can be
Combination therapy with chelator and an antioxidant affected by some uncertain factors However the
have never been used against fluoride toxicity evidence of interactions between fluoride and arsenic
However combination of vitamin C and E has been is inconclusive Results from an experimental study
reported to protect endometrial tissue via their on rabbits have suggested that there is an antagonistic
anti oxidant function on fluoride induced damage105 effect between fluoride and arsenic108 Therefore it is
As such there is no effective treatment for fluorosis quite probable that there are some interactions
Therefore prevention and control is the only between fluoride and arsenic on some biological
indexes Several studies have shown that combined Fluoride may be able to ameliorate the toxic effects
exposure of arsenic and fluoride causes oxidative of arsenic either through some strong bonding with
damage in the rat brain and also decreases activity arsenic or may be able to decrease its affinity for
of antioxidant enzymes and increased lipid active cell components Decreased toxicity in arsenic
peroxidation99 111 Effects of fluoride alone or in fluoride co exposure can be explained on the basis of
combination with arsenic on antioxidant activities are ionization Sodium fluoride is an ionic compound and
controversial117 Increased activity of SOD catalase gets completely ionized in aqueous solution Arsenic
and GPx and increased thiol status has also been has an empty d orbital of fairly low energy Arsenic
reported following combined exposure to these reacts directly and readily with halogens and some
toxicants There are few reports which suggest other non metals Arsenic predominately binds with
antagonism between arsenic and fluoride108 118 They halogen due to their electro negativity In trivalent
have reported antagonistic effects following arsenic oxidation state it shows SP3 hybridization and can
fluoride co exposure on antioxidant system in liver form AsF3 while in pentavalent oxidation state it
and kidney of rats It is therefore highly important to shows SP3d hybridization and forms AsF5 AsF3 exists
investigate the pattern and mechanism of combined in pyramidal structure while AsF5 exists as trigonal
arsenic and fluoride exposure on different organs bipyramidal structure AsF5 is a potent ion acceptor
There are few reports suggesting effects of forming AsF6 ions or more complex species
individual exposure to arsenic or fluoride on DNA Therefore fluoride can suppress the ionization of
damage and cellular deformities and relatively little sodium arsenite thereby reducing its toxicity But still
is known about their combined exposure on structure this hypothesis needs further investigations
and metabolism of various tissues A loss of DNA
integrity in the form of single strand breaks has been
Diagnosis of arsenic and fluoride toxicity Three
recorded during individual exposure of arsenic and
most commonly employed biomarkers used to
fluoride In arsenic and fluoride co exposed animals
identify and quantify arsenic exposure are total
DNA damage has been found to be less pronounced
compared to their individual exposure indicated by arsenic in hair or nails blood arsenic and total or
decreased comet tail119 Arsenic and fluoride both are speciated metabolites of arsenic in urine Because
known to cross blood brain barrier but during arsenic accumulates in keratin rich tissues such
combined exposure ROS and TBARS level in brain as skin hair and nails due to its high affinity for
remain unaltered suggesting some interaction between sulfhydryl groups arsenic level in hair and nails
these toxicants thereby inhibiting their free access in may be used as an indicator of past arsenic exposure
brain tissue Co exposure to arsenic and fluoride also Blood arsenic levels are highly variable Blood
led to a significant recovery in depleted GSH level of arsenic normally less than 1 g dl may be elevated
tissues as compared to arsenic alone exposed animals on acute intoxication but it is rapidly cleared from
which in turn again support the hypothesis that this the blood The most important diagnostic test
combination might have some antagonistic value for detecting arsenic exposure is urine arsenic
Concomitant exposure to arsenic and fluoride determination Since arsenic is rapidly metabolized
5mg kg has been found to show antagonistic effects and excreted into the urine total arsenic inorganic
on dopamine level and monoamine oxidase activity arsenic and the sum of arsenic metabolites inorganic
important neurotransmitters of our body which arsenic MMA DMA in urine have been used
might be due to possible interaction between them as biomarkers of recent arsenic exposure The levels
However synergistic effects have been observed of fluoride in plasma serum and urine have
during co exposure to arsenic and higher dose of been considered useful biomarkers for fluoride
fluoride 10 mg kg Such observations could be exposure75 120 121 There are several methods for
attributed to the possible interaction between arsenic determining fluoride toxicity Serum urine tooth
and fluoride which is exclusively concentration enamel bone and hair analyses It has been
dependent It can also be suggested that at low suggested that the fluoride concentration in nails and
concentration fluoride ions are sufficient enough to hair can also be used as a marker of fluoride
react with arsenic however at high concentration the exposure122 123 There is however no specific
effects are predominantly of free fluoride ions biomarker to examine the condition of combined
compared to arsenic119 arsenic fluoride exposure
Conclusion 11 ATSDR Toxicological Profile for arsenic Agency for Toxic
There is paucity of experimental data on the Substances and Disease Registry ATSDR TP 88 02 U S
Public Health Service Atlanta GA 1989
interactive effects of sodium arsenite and sodium 12 Huang Y Z Qian X C Wang G Q Xiao B Y Ren D D Feng
fluoride when administered concomitantly on the Z Y Wu J Y Xu R J Zhang F E Endemic chronic
major organs There is relatively no conclusive arsenism in Xinjiang Chin Med J 98 1985 219
experimental evidence if the combined exposure will 13 Valko M Izakovic M Mazur M Rhodes C J Telser J
Role of oxygen radicals in DNA damage and cancer
led to synergistic or antagonistic effects in animals incidence Mol Cell Biochem 266 2004 37
Also the current management of acute and chronic 14 Flora S J S Bhadauria S Kannan G M Singh N Arsenic
arsenic poisoning relies on supportive care and induced oxidative stress and role of antioxidant
chelation therapy however till date there is no supplementation during chelation A Review J Environ Biol
effective treatment for chronic fluoride poisoning 28 2007 333
15 Rin K Kawaguchi K Yamanaka K Tezuka M Oku N
Thus an attempt should be made to explore the Okada S DNA strand breaks induced by dimethylarsenic
researches which provide information regarding the acid a metabolite of inorganic arsenics are strongly enhanced
mode of action to these toxicants and possible by superoxide anion radicals Biol Pharm Bull 18 1995 45
preventive and therapeutic measure to reduce their 16 Yamanaka K Hoshino M Okanato M Sawamura R
Hasegawa A Okada S Induction of DNA damage by
toxic burden from the human population dimethylarsine a metabolite of inorganic arsenics is for the
major part likely due to its peroxyl radical Biochem Biophys
Acknowledgement Res Commun 168 1999 58
The authors thank the Director for his support and 17 Shi H L Shi X L Liu K J Oxidative mechanism of arsenic
suggessions The author SC acknowledge DRDO toxicity and carcinogenesis Mol Cell Biochem 255 2004 67
18 Yang C Frenkel K Arsenic mediated cellular signal
India for the award of Senior Research Fellowship transduction transcription factor activation and aberrant
gene expression implications in carcinogenesis J Environ
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