ReviewArsenic and selenium toxicity and their interactive effects in humans
Graphical abstract
Synergistic and antagonistic relation between As and Se toxicity in humans.
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.
References (180)
- et al.
Abnormal DNA repair in selenium-treated human cells
Mutat Res
(2004) - et al.
Molecular events associated with arsenic-induced malignant transformation of human prostatic epithelial cells: aberrant genomic DNA methylation and K-ras oncogene activation
Toxicol Appl Pharmacol
(2005) - et al.
SLC13 family of Na+-coupled di-and tri-carboxylate/sulfate transporters
Mol Aspects Med
(2013) - et al.
Prevention of cytotoxic effects of arsenic by short-term dietary supplementation with selenium in mice in vivo
Mutat Res
(1999) - et al.
Chromosome damage induced by selenium salts in human peripheral lymphocytes
Toxicol In Vitro
(2000) - et al.
The paradox of arsenic: molecular mechanisms of cell transformation and chemotherapeutic effects
Crit Rev Oncol Hematol
(2002) - et al.
Comparative study of p38 MAPK signal transduction pathway of peripheral blood mononuclear cells from patients with coal-combustion-type fluorosis with and without high hair selenium levels
Int J Hyg Environ Health
(2010) - et al.
DRAM, a p53-induced modulator of autophagy, is critical for apoptosis
Cell
(2006) - et al.
Effect of selenite on the disposition of arsenate and arsenite in rats
Toxicology
(2003) - et al.
Methylated trivalent arsenicals are potent inhibitors of glucose stimulated insulin secretion by murine pancreatic islets
Toxicol Appl Pharmacol
(2013)
Arsenite and monomethylarsonous acid generate oxidative stress response in human bladder cell culture
Toxicol Appl Pharmacol
The protective role of selenium on genetic damage and on cancer
Mutat Res
Arsenic-selenium and mercury-selenium bonds in biology
Coord Chem Rev
On-column formation of arsenic-glutathione species detected by size-exclusion chromatography in conjunction with arsenic-specific detectors
J Chromatogr B
Synthesis, X-ray absorption spectroscopy and purification of the seleno-bis (S -glutathionyl) arsinium anion from selenide, arsenite and glutathione
J Organomet Chem
Selenoproteins that function in cancer prevention and promotion
BBA-Gen Subjects
Role of oxidative damage in the genotoxicity of arsenic
Free Radic Biol Med
Zinc deficiency, DNA damage and cancer risk
J Nutr Biochem
Cellular uptake of trivalent arsenite and pentavalent arsenate in KB cells cultured in phosphate-free medium
Toxicol Appl Pharmacol
Low selenium status affects arsenic metabolites in an arsenic exposed population with skin lesions
Clin Chim Acta
Dysfunction of rat liver mitochondria by selenite: induction of mitochondrial permeability transition through thiol-oxidation
Biochem Biophys Res Commun
Induction of the mitochondrial permeability transition by selenium compounds mediated by oxidation of the protein thiol groups and generation of the superoxide
Biochem Pharmacol
Serum selenium, vitamin antioxidants, and cardiovascular mortality: a 9-year follow-up study in the Netherlands
Am J Clin Nutr
Evaluation of selenium in biological sample of arsenic exposed female skin lesions and skin cancer patients with related to non-exposed skin cancer patients
Sci Total Environ
Mechanisms of inhibition of zinc-finger transcription factors by selenium compounds ebselen and selenite
J Inorg Biochem
Selenium: from cancer prevention to DNA damage
Toxicology
Toxicity and mutagenicity of selenium compounds in Saccharomyces cerevisiae
Mutat Res Fundam Mol Mech Mutagen
Effects of arsenic, mercury, thallium, and lead on selenium metabolism in rats
Toxicol Appl Pharmacol
Dissociation of the genotoxic and growth inhibitory effects of selenium
Biochem Pharmacol
Arsenic alters cytosine methylation patterns of the promoter of the tumor suppressor gene p53 in human lung cells: a model for a mechanism of carcinogenesis
Mutat Res
Arsenic in the geosphere – a review
Sci Total Environ
Hepatoprotective role and antioxidant capacity of selenium on arsenic-induced liver injury in rats
Exp Toxicol Pathol
The influence of arsenic and certain other elements on the Toxicity of seleniferous grains three figures
J Nutr
Characteristics of transport of selenoamino acids by epithelial amino acid transporters
Chem Biol Interact
Methylation and demethylation of intermediates selenide and methylselenol in the metabolism of selenium
Toxicol Appl Pharmacol
Toxicity, metabolism and absorption of selenite by isolated rat hepatocytes
Toxicology
Selenite inhibits the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) through a thiol redox mechanism
J Biol Chem
Arsenic exposure and hypertension: a systematic review
Environ Health Perspect
Arsenic trioxide and paclitaxel induce apoptosis by different mechanism
Cell Cycle
Roles for p53 in growth arrest and apoptosis: putting on the brakes after genotoxic stress
Oncogene
Decreased DNA repair gene expression among individuals exposed to arsenic in United States drinking water
Int J Cancer
Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic
Environ Health Perspect
Reactive oxygen species: metabolism, oxidative stress, and signal transduction
Annu Rev Plant Biol
Se concentrations in serum and angiographically defined coronary artery disease are uncorrelated
Clin Chem
DNA sequencing of a mouse liver protein that binds selenium: implications for selenium's mechanism of action in cancer prevention
Carcinogenesis
Multiple roles of the tumor suppressor p53
Curr Opin Oncol
Oral selenate improves glucose homeostasis and partly reverses abnormal expression of liver glycolytic and gluconeogenic enzymes in diabetic rats
Diabetologia
Interaction of selenium compounds with zinc finger proteins involved in DNA repair
Eur J Biochem
Selenium and diabetes: more bad news for supplements
Ann Intern Med
Serum selenium and diabetes in US adults
Diabetes Care
Cited by (320)
A regulatory module comprising G3BP1-FBXL5-IRP2 axis determines sodium arsenite-induced ferroptosis
2024, Journal of Hazardous MaterialsEffects of temperature on the migration behaviour of arsenic and chromium in tannery sludge under CO<inf>2</inf> gasification
2024, Journal of Hazardous Materials