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Treating Arsenic Exposure

Considering the advancements of the twenty first century, it certainly is farcical that

simple things like access to clean drinking water are not available to many people on Earth.

Anthropogenic environmental degradation has been to blame for many disasters on earth, which

includes arsenic contamination that is - and will continue - affecting people negatively (Arsenic

in Drinking Water, 2001). Agricultural irrigation, arsenic pesticides, and industrial irrigation are

prime examples, but there are also natural processes that exacerbate the contamination of arsenic.

Prevention of contamination is not widely taught (Arsenic Toxicity, 2010) and I feel that

researching and warning people that are doing the contaminating, as well as those being affected,

can substantially lower the rate dangerous and/or lethal levels of arsenic exposure. This pertains

to my future patients because one of my goals in life is to participate in a type of association like

Doctors Without Borders, and arsenic poison - heavy metal poisoning in general - is a big

problem in many third-world countries. My future patients could potentially be people who have

been contaminated through one of many different sources of arsenic poisoning.

Acute and chronic arsenic exposure can bring about different symptoms, but both are

fairly common within regions of countries that are very poor and desolate; this does not mean

that it is an isolated issue among third-world countries. In fact, arsenic has been noted as a

worldwide problem that can possibly affect everyone. In addition, the goal of teaching

prevention rather than treatment is very relevant in this situation. Encouraging the education of

people who face these problems daily is vital to combating heavy metal poisoning in general, and

potentially saving millions of lives.This interests me because environmental degradation is

something that I strive to combat. I pride myself in standing for the trees because they do not
have voices to defend themselves. When I mention the trees, I mean the environment in general;

from global warming to the nominal by comparison death of nanobacteria in the ocean.

I obviously cannot single handedly stop the anthropogenic exacerbation of global

warming or air pollution, but what I can do is encourage the people around me to recycle their

paper, or conserve water and energy. However insignificant this may seem, it is a lot more than

what most people are doing today. Globally, the United States is behind many countries that are

substantially more environmentally sound and friendly. In addition, I can write about the

consequences of degradation in this research article that will educate whoever reads it. I am not

looking to change the world with this article, but changing the opinion of at least one person is a

big step towards properly speaking for the voiceless.

To effectively solve a problem, it is vital to attack it at the root of the source. Arsenic

stems from many different sources including industrial processes. It is an infamous byproduct

of the smelting of many metal ores like cobalt, lead, and gold (Arsenic Toxicity, 2010, para. 5).

People exploiting the environment for monetary gain happens frequently, and the lack of any

real punishment has exacerbated the problem. The shortage of clean drinking water has also

encouraged the increase of drilling tube wells to find clean water in Bangladesh. Ironically, these

processes also account for a major portion of the documented occurrences of arsenic poisoning

because unbeknownst to everyone, these tube-wells were carrying arsenic-contaminated water

into drinking sources (The Water Page, 2001, para. 4). The resulting positive-feedback loop

puts people in tough situations because stopping the drilling would result in inaccessibility to

water for a majority of the population, and continuing the drilling may satisfy water needs, but it

will only enhance the arsenic poisoning problem. Bangladesh has become synonymous with
mass arsenic poisoning because of natural processes like pyrite oxidation and oxyhydroxide

reduction that release arsenic (The Water Page, 2001, para. 7). In addition, agriculture has also

been a big contributor to arsenic contamination because the dangerous inorganic arsenic is

released during the manufacturing of widely-used pesticides (The Water Page, 2001, para. 6).

In their research, Flora, Bhadauria, Pachauri, & Yadav (2012) identify the following

elements in the experiment: Monoisoamyl DMSA (MiADMSA) - a monoester of

Dimercaptosuccinic acid (DMSA) - is used to treat chronic arsenic poisoning in male Wistar rats.

The drug was given to the subjects orally or through intraperitoneal (IP) administration, and the

effects were monitored closely through pharmacokinetic analysis. MiADMSA is a

water-soluble lipophilic chelating agent has emerged as a promising drug for the treatment of

arsenic (Flora et al., 2012, para.1). Twenty five Wistar rats were divided into 5 groups: the

control group that received saline, two groups that received MiADMSA orally, through doses of

50 or 100 mg/kg once daily, respectively, and the last two groups received MiADMSA through

IP administration at doses of 50 or 100 mg/kg, respectively.

After arsenic contamination, decreased levels of hepatic Glutathione (GSH) and

hemoglobin (Hb) were recorded, the 50 mg/kg dose of MiADMSA was observed to be most

effective in reversing arsenic-induced altered biochemical variables in blood (Flora et al., 2012,

para. 24). Further blood tests revealed that initial decreases in Red blood cell counts and

hematocrit levels were reversed by the oral administration of MiADMSA (Flora et al., 2011,

para. 25). Renal and hepatic oxidative stress, defined as . . . a disturbance in the balance

between the production of reactive oxygen species (free radicals) and antioxidant defenses. . . (

Betteridge, 2000, p. 12) show a positive response to the drug treatment, indicating that the drug
treatment reduced the oxidative stress that arsenic poisoning imposes on body organs. On a

molecular level, oral administration of MiADMSA was able to help fix the damage caused by the

contamination of arsenic.

In conclusion, Flora et al., determine that both modes of administration were effective,

but IP administration is a better fit for acute arsenic poisoning, and chronic poisoning can be

better treated by oral MiADMSA treatment .The reason being that with chronic poisoning, the

arsenic is more likely to dissipate further into the cells, and the lipophilicity of MiADMSA

allows it to travel intracellularly to clean up the arsenic (Flora et al., 2011, para. 5). From the

pharmacokinetic analysis, it is noted that the oral administration of the drug is shown to stay

within the body longer, enabling it to better counteract the chronic arsenic exposure. From this

experiment, it can be concluded that MiADMSA is a better alternative than DMSA as a

treatment for arsenic poisoning. Furthermore, the oral administration is a better treatment for

chronic arsenic exposure while the IP administration is better suited for the treatment of acute

arsenic exposure (Flora et al., 2012, para. 37).

In the article Effects of glutathione on the in vivo metabolism and oxidative stress of

arsenic in mice, Wang, Lin, Li, & Sun, (2016) set out to learn the role that Glutathione (GSH)

plays in Arsenic methylation - the primary method of metabolizing arsenic - as well as reducing

the levels of arsenic-related oxidative stress . The experiment performed consisted of 36 female

albino mice test subjects that were divided into six groups of six. All groups except the control

were given water that was contaminated with arsenic, and after ten days, the subjects were

injected intraperitoneally with different levels of GSH or Buthionine Sulfoximine (BSO). At the

end of the experiment, the mice were separated into individual cages, enabling 24 hour collective
urine test to before performed for further analysis. Percentages of iAs (inorganic arsenic),

monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured in the urine

and liver to evaluate the effect of GSH or BSO on the methylation of arsenic (Wang et al., 2016).

Results showed that the total As ingested from drinking the contaminated water was 5.9

to 8.01 mg As/kg b.w./day (Wang et al., 2016, para 7). After the initial rise in arsenic species -

iAs, MMA, and DMA - in the liver, the GSH administration proved the best in decreasing the

arsenic levels. FMR (first methylation ratio) and SMR (second methylation ratio) were higher in

urine than in the liver - meaning that arsenic methylation happens in extrahepatic tissues as

well.FMR and SMR represented the capability of methylation from iAs to MMA, and from

MMA to DMA, respectively (Wang et al., 2016, para. 9). In addition, urinary FMR and SMR

are representative of the entire bodys methylation capability because arsenic metabolites are

ultimately excreted into the urine (Wang et al., 2016). In addition, the mechanism of arsenic

poisoning in the body is intertwined with arsenic-induced oxidative stress, thus GSH is a highly

effective medicine under both circumstances. It is clear through the results that exogenous GSH

consistently reversed the ill effects of arsenic poisoning that consisted of decreased of blood and

hepatic GSH, as well as a reduction of the mices overall antioxidant capacity. From this

experiment, it is concluded that the . . . appropriate administration of exogenous GSH could

promote arsenic methylation, accelerate arsenic excretion . . . and enhance the bodys antioxidant

capacity (Wang et al., 2016, para 6).

Despite the effectiveness of the treatments mentioned above, there is no better treatment

in the world for any problem better than prevention. Perhaps the most overstated solution is to

find alternative sources of water to replace those that have elevated arsenic concentrations above
the 10 parts per billion or 0.01 milligrams per liter limit that the EPA and WHO deem safe for

consumption, respectively (The Water Page, 2001, para. 5). The fact that Bangladesh - and many

other third-world countries - place their limits to many water pollutants at least five fold of what

they are in more developed countries, is truly reflective of the global crisis that is occurring in

the world (The Water Page. 2001). To combat the variations in limits, it is important to have

globally uniform laws that are vital in fighting water pollution in general, and arsenic pollution

will follow suit. In addition, testing high risk areas for arsenic concentrations is important

because people need to be aware of what is in the water they are drinking. Demarcating unsafe

water sources can help reduce the rate of arsenic contamination. Education is the key to

prevention because knowledgeable citizens will know to stop any activity that exacerbates the

problem. They will also stay away from high risk areas in addition to educating the people

around them.

Arsenic exposure has notable health effects like skin lesions and secondary cancers. To

combat the residual effects of As,, the chemoprotective potential of Vernonia amygdalina

against sodium arsenite-induced genotoxicity and hepatotoxicity (Adetutu, Oyewo, &

Adesokan, 2013, ?) is evaluated in the following experiment. Twenty male Wistar rats were

divided into four even groups; The first two groups were given two doses of 50 and 100 mg/kg

per body weight for seven consecutive days, then were given a single dose of sodium arsenic

intraperitoneally. The third group a was a negative control that received distilled water, the

fourth was a positive control group that only received sodium arsenite. As part of the analysis,

blood samples of the mice were examined for arsenic-induced micronuclei because small nuclei

can be a sign of genotoxicity - damage to an organism's genetic information (Adetutu et al.,


2013). Results revealed a substantially higher rate of micronuclei in the negative control group

while Pretreatment with 50 mg/kg V. amygdalina leaf extract significantly reduced sodium

arsenite induced MN in bone marrow by 70%. . . (Adetutu et al., 2013, ?).

The preventative treatment of V. amygdalina proved to be very efficient in inhibiting the

arsenic-induced micronuclei of the mices bone marrow blood. In addition, a histology

examination of the mices livers revealed that the mice treated with V. amygdalina presented

with less necrosis than those that did not get the treatment. This is further explained because

The effects of V. amygdalina leaf extract discussed until here are important mediators to have

beneficial response to prevent liver fibrosis induced by sodium arsenite administration and may

have an impact in the prevention of diseases (Adetutu et al., 2013, ?). This was determined by

the analysis for GGT (Gamma-glutamyl transpeptidase) and ALP (Alkaline phosphatase)

because they are the main markers for liver damage. In the mice treated with V. amygdalina,

both GGT and ALP levels were normal after an initial rise due to the sodium arsenite. It is noted

that V. amygdalina may contain antioxidant compounds that combat the reactive species

generated by sodium arsenite, and as a result, it reduces the toxicity (Adetutu et al., 2013). The

exact mechanism of V. amygdalina chemoprotective characteristic against sodium arsenite is not

known.

In analyzing treatments for arsenic poisoning, the usage of MiADMSA, GSH and BSO,

and the preemptive usage of V. amygdalina have been successful. The MiADMSA trials seemed

to give a legitimate option for both chronic and acute As poisoning. A subject group of twenty

five rats seems sufficient to give proper results. For the GSH and BSO trial, the methylation

capability was measured by the concentration of As species. In addition, it measured the effect
that each treatment had on the As induced oxidative stress because it is believed that oxidative

stress is closely related to the methylation capability of an organism. The subject size is

sufficient in this study as well, enabling the results to be more trustworthy. The results did

indicate that with appropriate administration the application of GSH and BSO would be

effective but some of the areas that need the treatment the most lack appropriate health centers

they can turn to (Adetutu et al., para 9). With many people struggling to feed their families, they

might disregard the treatment, hindering the successful effects of the treatments. A medication

with simple instructions is what will work best.

The one prevention method studied is the preemptive treatment of Vernonia amygdalina

showed positive results by reducing the sodium arsenite-induced micronuclei of the bone marrow

blood in the mice. The subject size for this trial was of sufficient size, good enough to trust the

results. In addition to reducing genotoxicity, the treatment also reduced the hepatotoxicity of the

mice. It is important for people to know these possible treatments for Arsenic contamination

because it is a global problem. It might be more severe in desolate countries, but everyone can be

affected.

This data will influence my future career because as noted in the aforementioned

paragraph, a goal in life of mine is to participate in a program that helps people in third-world

countries. Knowing that As poisoning is severe especially in Bangladesh, it can be a possible

location that I can be sent to, to possibly administer the treatments mentioned above.

Researching about the prevention methods has strengthened my desire to help people in need

because simple prevention methods can save many lives. If I can help save one person from a life
plagued with health effects from ingesting As, I will be ecstatic because it will just be the start

for many more.

References

Adetutu, A., Oyewo, E. B., & Adesokan, A. A. (2013). Protective effects of Vernonia

amygdalina against sodium arsenite-induced genotoxicity in rat. Pharmacognosy

research, 5(3), 207.

Betteridge, D. J. (2000). What is oxidative stress?. Metabolism, 49(2), 3-8.definition of

oxidative stress

Arsenic toxicity.. (2010). Retrieved from

https://www.atsdr.cdc.gov/csem/csem.asp?csem=1&po=5

Flora, S. J., Bhadauria, S., Pachauri, V., & Yadav, A. (2012). Monoisoamyl 2,

3-Dimercaptosuccinic Acid (MiADMSA) Demonstrates Higher Efficacy by Oral Route


in Reversing Arsenic Toxicity: A Pharmacokinetic Approach. Basic & clinical

pharmacology & toxicology, 110(5), 449-459. DOI: 10.1111/j.1742-7843.2011.00836.x

Arsenic in drinking water. (2001). Retrieved from http://www.thewaterpage.com/arsenic.htm

Wang, D., Lin, L., Li, X., & Sun, G. F. (2015). Effects of glutathione on the in vivo metabolism

and oxidative stress of arsenic in mice. The Journal of toxicological sciences, 40(5),

577-583. http://doi.org/10.2131/jts.40.577

Arsenic. (2016). Retrieved from http://www.who.int/mediacentre/factsheets/fs372/en/

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