Elsevier

Environment International

Volume 69, August 2014, Pages 148-158
Environment International

Review
Arsenic and selenium toxicity and their interactive effects in humans

https://doi.org/10.1016/j.envint.2014.04.019Get rights and content

Highlights

  • As and Se are both carcinogens and anticarcinogens.

  • Reactive oxygen species play a role in their toxicity.

  • Glutathione and S-adenosylmethionine are important in their detoxification.

  • Synergistic and antagonistic effects exist between As and Se toxicity.

  • Formation of [(GS)2AsSe] reduces both As and Se toxicity.

Abstract

Arsenic (As) and selenium (Se) are unusual metalloids as they both induce and cure cancer. They both cause carcinogenesis, pathology, cytotoxicity, and genotoxicity in humans, with reactive oxygen species playing an important role. While As induces adverse effects by decreasing DNA methylation and affecting protein 53 expression, Se induces adverse effects by modifying thioredoxin reductase. However, they can react with glutathione and S-adenosylmethionine by forming an As–Se complex, which can be secreted extracellularly. We hypothesize that there are two types of interactions between As and Se. At low concentration, Se can decrease As toxicity via excretion of As–Se compound [(GS3)2AsSe], but at high concentration, excessive Se can enhance As toxicity by reacting with S–adenosylmethionine and glutathione, and modifying the structure and activity of arsenite methyltransferase. This review is to summarize their toxicity mechanisms and the interaction between As and Se toxicity, and to provide suggestions for future investigations.

Graphical abstract

Synergistic and antagonistic relation between As and Se toxicity in humans.

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Introduction

Arsenic (As) is ubiquitous in the environment and it exists in four oxidation states: arsenate (+ 5), arsenite (+ 3), elemental arsenic (0) and arsine (− 3). It is released to the environment through both natural processes and anthropogenic activities. Arsenic is widely distributed in the earth, ranking 20th in abundance in the earth’s crust. It has been widely used in agriculture as pesticides and wood preservatives (Sharma and Sohn, 2009). On the one hand, As has been used to cure acute promyelocytic leukemia in humans (Miller et al., 2002). On the other hand, As causes adverse health effects including cancers in human. At present, millions of people worldwide suffer from chronic arsenic poisoning (Hughes et al., 2011, Rodríguez-Lado et al., 2013) mainly due to consumption of As-contaminated water and food.

Arsenic contamination in the environment is becoming a serious public health problem in several regions. It is known that arsenite (AsIII) is more toxic than arsenate (AsV), with inorganic As being more toxic than organic As (Petrick et al., 2000). However, different organic As species have different toxicity. For example, as final As metabolites, monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) are less toxic than inorganic arsenic, whereas the toxicity of intermediate metabolites such as monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII) are much more toxic than inorganic arsenic (Petrick et al., 2000). The toxicity of various arsenic species increases in the order of AsV < MMAV < DMAV < AsIII < MMAIII  DMAIII.

Selenium (Se) is a metalloid in group VIA and an analog of sulfur, with four oxidation states in nature: selenate (+ 6), selenite (+ 4), elemental selenium (0), and selenide (− 2) (Tinggi, 2003). Unlike As, Se is an essential nutrient for humans, animals, and bacteria. It is important for many cellular processes because it is a component of several selenoproteins and selenoenzymes with essential biological functions (Table 2) (Letavayová et al., 2008). Furthermore, many studies demonstrated that proper doses of Se can prevent cancers in animals and humans (Clark et al., 1996, Ganther, 1999). However, it is toxic at levels slightly above homeostatic requirement (Zhang et al., 2014). Similar to As where AsV is less toxic than AsIII, SeVI is less toxic than SeIV in eukaryote and prokaryote (Rosen and Liu, 2009). Abbreviations are listed in Table 1.

It is of considerable interest to examine their dual role as a toxicant and nutrient. Se and As are both metalloids with similar chemical properties, playing dual roles regarding cancer. Arsenic is known for its carcinogenicity, yet it is also used in treating certain cancers. Similarly, Se is a known anticarcinogen, but it also triggers cancer. Much research was done to understand their carcinogenic mechanisms (Bansal et al., 1990, Rossman, 2003), and the relation between cancer and their dual roles as carcinogen and anticarcinogen (Bode and Dong, 2002, Chakraborti et al., 2003). However, there still exist contradictory results as both synergistic and antagonistic toxicity between As and Se has been reported (Biswas et al., 1999).

Hence the relation between As and Se has attracted increasing attention. This review summarizes and compares their toxicity mechanisms to better understand the relation between As and Se toxicity.

Section snippets

Arsenic

In terrestrial environment, As is mainly present as inorganic As, which exists as pentavalent (AsV) under aerobic condition and trivalent (AsIII) under anaerobic environment (Matschullat, 2000). However, AsIII and AsV exert toxicity differently.

AsIII is typically present as a neutral species (As(OH)3°, pKa = 9.2) in aqueous solution at physiological pH (Gailer, 2007). Due to its structural similarity to glycerol, AsIII can be transported into cells through aquaglycerolporins, a pore protein for

Arsenic and selenium toxicity

Several review articles documented arsenic toxicity in humans and animals (Fig. 3). Arsenic is a carcinogen, causing skin, bladder, liver, and lung cancers (Tapio and Grosche, 2006, Yoshida et al., 2004). Arsenic induces epidemiological toxicity, damaging organisms by producing excess ROS (Shi et al., 2004b, Wang et al., 2001). Arsenic is also cytotoxic (Suzuki et al., 2007, Zhang et al., 2003) and genotoxic (Benbrahim-Tallaa et al., 2005, Gentry et al., 2010). In addition, it is well known

Antagonistic and synergistic relation between As and Se toxicity

Although they are both trace elements, As and Se possess different uptake pathways by cells. While the uptake of AsV into cells is by the phosphate transporter, SeVI uptake is via the sulfate transporter. SeIV and AsIII do not compete through aquaglyceroprins (Rosen and Liu, 2009). Although they won’t compete to cross into the cells, they can be toxic to each other. Some reported that Se alleviates As toxicity (Biswas et al., 1999, Selvaraj, 2012) whereas others found that Se enhances As

Concluding remarks

This review summarized the toxicity mechanisms and the relation between As toxicity and Se toxicity in animals and humans and provided suggestions for future research. According to literature, ROS play a fundamental role in As- and Se- induced toxicity in humans. Furthermore, As also induces adverse effects by decreasing DNA methylation and affecting protein 53 expression. Se exerts adverse effects by modifying thioredoxin reductase. Meanwhile, much research has focused on the interactions

Acknowledgements

This research was supported in part by Jiangsu Provincial Innovation Project.

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