The blood toll of arsenic: addressing hematological disorders and future directions
DOI:
https://doi.org/10.18203/2394-6040.ijcmph20260721Keywords:
Arsenic, Hematology, Anaemia, Echinocyte, Leucocyte, NutraceuticalAbstract
Arsenic contamination is a critical global health threat, with the hematological system being a primary target of its toxicity. This review synthesized current scientific literature from PubMed and Web of Science to document arsenic-induced hematotoxicity and evaluate the efficacy of various amelioration strategies. Inorganic arsenic uses a variety of cell membrane transporter proteins, including different proton and phosphate transporters and the anion exchanger Band 3 protein for entry into the cell. Glucose transporters, aquaporins, and ATP-binding cassette transporters are used for the extrusion of arsenic. The markers of hematotoxicity are shown to be severely altered in arsenic-treated fish and mammalian models. Moreover, significant alterations, including DNA methylation, altered T cell populations, increased PBMCs associated with marked neutropenia, apoptosis of blood monocytes, etc., were observed in leucocytes. Transformation of discoidal erythrocytes to echinocytes, followed by spheroechinocytes and eryptosis, is considered an impending cause for arsenic-induced anaemia. Chelating agents, various plant extracts, and/or nutraceutical agents such as ascorbic acid, α-tocopherol, and lipoic acid are found to be protective against arsenic-induced hematotoxicity. This comprehensive documentation offers a clear overview of the research conducted in this vital area, indicating that the management of arsenic-induced hematotoxicity is achievable with the aforementioned compounds or extracts. A comparative analysis using secondary data is essential to ascertain the potency and efficacy of various ameliorative agents. This would provide a complete understanding of hematological arsenicosis and guide future directions for remedial measures.
Metrics
References
WHO. Arsenic in Drinking-Water. Available at: https://www.who.int/publications/i/item/arsenic-in-drinking-water-background-document-for-development-of-who-guidelines-for-drinking-water-quality. Accessed on 21 August 2025.
Roy S, Samaddar S. Review On Arsenic Toxicity: Effect On Human Health And Biochemical Aspects. Int J Chem Environ Sci. 2021;3(1). DOI: https://doi.org/10.15864/268963821834540164
Calatayud M, Gimeno J, Vélez D, Devesa V, Montoro R. Characterization of the intestinal absorption of arsenate, monomethylarsonic acid, and dimethylarsinic acid using the caco-2 cell line. Chem Res Toxicol. 2010;23(3):547-56. DOI: https://doi.org/10.1021/tx900279e
Kala S V., Neely MW, Kala G. The MRP2/cMOAT transporter and arsenic-glutathione complex formation are required for biliary excretion of arsenic. J Biol Chem. 2000;275(43):33404-8. DOI: https://doi.org/10.1074/jbc.M007030200
Garbinski LD, Rosen BP, Chen J. Pathways of arsenic uptake and efflux. Environ Int. 2019;126:585-97. DOI: https://doi.org/10.1016/j.envint.2019.02.058
Vasken Aposhian H, Zakharyan RA, Avram MD, Sampayo-Reyes A, Wollenberg ML. A review of the enzymology of arsenic metabolism and a new potential role of hydrogen peroxide in the detoxication of the trivalent arsenic species. Toxicol Appl Pharmacol. 2004;198(3):327-35. DOI: https://doi.org/10.1016/j.taap.2003.10.027
Naranmandura H, Suzuki KT. Identification of the major arsenic-binding protein in rat plasma as the ternary dimethylarsinous-hemoglobin-haptoglobin complex. Chem Res Toxicol. 2008;21(3):678-85. DOI: https://doi.org/10.1021/tx700383g
Surdu S, Bloom MS, Neamtiu IA. Consumption of arsenic-contaminated drinking water and anemia among pregnant and non-pregnant women in northwestern Romania. Environ Res. 2015;140:657-60. DOI: https://doi.org/10.1016/j.envres.2015.05.020
Kile ML, Baccarelli A, Hoffman E. Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes. Environ Health Perspect. 2012;120(7):1061-6. DOI: https://doi.org/10.1289/ehp.1104173
Xia S, Sun Q, Zou Z. Ginkgo biloba extract attenuates the disruption of pro-and anti-inflammatory T-cell balance in peripheral blood of arsenicosis patients. Int J Biol Sci. 2020;16(3):483-94. DOI: https://doi.org/10.7150/ijbs.39351
Martin-Chouly C, Morzadec C, Bonvalet M, Galibert MD, Fardel O, Vernhet L. Inorganic arsenic alters expression of immune and stress response genes in activated primary human T lymphocytes. Mol Immunol. 2011;48(6-7):956-65. DOI: https://doi.org/10.1016/j.molimm.2011.01.005
Biswas D, Banerjee M, Sen G. Mechanism of erythrocyte death in human population exposed to arsenic through drinking water. Toxicol Appl Pharmacol. 2008;230(1):57-66. DOI: https://doi.org/10.1016/j.taap.2008.02.003
Delnomdedieu M, Basti MM, Otvos JD, Thomas DJ. Reduction and binding of arsenate and dimethylarsinate by glutathione: a magnetic resonance study. Chem Biol Interact. 1994;90(2):139-55. DOI: https://doi.org/10.1016/0009-2797(94)90099-X
Rael LT, Ayala-Fierro F, Carter DE. The effects of sulfur, thiol, and thiol inhibitor compounds on arsine- induced toxicity in the human erythrocyte membrane. Toxicol Sci. 2000;55(2):468-77. DOI: https://doi.org/10.1093/toxsci/55.2.468
Hatlelid KM, Brailsford C, Carter DE. Reactions of arsine with hemoglobin. J Toxicol Environ Health. 1996;47(2):145-57. DOI: https://doi.org/10.1080/009841096161852
Chatterjee D, Bhattacharjee P, Sau TJ. Arsenic exposure through drinking water leads to senescence and alteration of telomere length in humans: A case-control study in West Bengal, India. Mol Carcinog. 2015;54(9):800-9. DOI: https://doi.org/10.1002/mc.22150
Bombarde O, Boby C, Gomez D. TRF2/RAP1 and DNA-PK mediate a double protection against joining at telomeric ends. EMBO J. 2010;29(9):1573-84. DOI: https://doi.org/10.1038/emboj.2010.49
Salgado-Bustamante M, Ortiz-Pérez MD, Calderón-Aranda E. Pattern of expression of apoptosis and inflammatory genes in humans exposed to arsenic and/or fluoride. Sci Total Environ. 2010;408(4):760-7. DOI: https://doi.org/10.1016/j.scitotenv.2009.11.016
Hall M, Gamble M, Slavkovich V. Determinants of arsenic metabolism: Blood arsenic metabolites, plasma folate, cobalamin, and homocysteine concentrations in maternal-newborn pairs. Environ Health Perspect. 2007;115(10):1503-9. DOI: https://doi.org/10.1289/ehp.9906
Peterson DP, Bhattacharyya MH. Hematological responses to arsine exposure: Quantitation of exposure response in mice. Toxicol Sci. 1985;5(3):499-505. DOI: https://doi.org/10.1093/toxsci/5.3.499
Akter R, Neelotpol S, Kabir MT. Effect of Allium sativum methanol extract in amelioration of arsenic-induced toxicity in Swiss albino mice. Phytomedicine Plus. 2022;2(1):100192. DOI: https://doi.org/10.1016/j.phyplu.2021.100192
Ferzand R, Gadahi JA, Saleha S, Ali Q. Histological and haematological disturbance caused by arsenic toxicity in mice model. Pakistan J Biol Sci. 2008;11(11):1405-13. DOI: https://doi.org/10.3923/pjbs.2008.1405.1413
Kannan GM, Tripathi N, Dube SN, Gupta M, Flora SJS. Toxic effects of arsenic (III) on some hematopoietic and central nervous system variables in rats and guinea pigs. J Toxicol - Clin Toxicol. 2001;39(7):675-82. DOI: https://doi.org/10.1081/CLT-100108508
Gupta R, Kannan GM, Sharma M, Flora SJS. Therapeutic effects of Moringa oleifera on arsenic-induced toxicity in rats. Environ Toxicol Pharmacol. 2005;20(3):456-64. DOI: https://doi.org/10.1016/j.etap.2005.05.005
Mishra D, Flora SJS. Quercetin administration during chelation therapy protects arsenic-induced oxidative stress in mice. Biol Trace Elem Res. 2008;122(2):137-47. DOI: https://doi.org/10.1007/s12011-007-8064-9
Tandon N, Roy M, Roy S, Gupta N. Protective effect of Psidium guajava in arsenic-induced oxidative stress and cytological damage in rats. Toxicol Int. 2012;19(3):245-9. DOI: https://doi.org/10.4103/0971-6580.103658
Pereira JA, Chattopadhyay S, Law S. Exposure of Arsenic Associated with Cellular Turnover and Apoptosis Profile in the Bone Marrow of Mice Including Stem/Progenitor Population. Proc Zool Soc. 2024;77(1):89-104. DOI: https://doi.org/10.1007/s12595-023-00511-3
Kavitha C, Malarvizhi A, Senthil Kumaran S, Ramesh M. Toxicological effects of arsenate exposure on hematological, biochemical and liver transaminases activity in an Indian major carp, Catla catla. Food Chem Toxicol. 2010;48(10):2848-54. DOI: https://doi.org/10.1016/j.fct.2010.07.017
Lavanya S, Ramesh M, Kavitha C, Malarvizhi A. Hematological, biochemical and ionoregulatory responses of Indian major carp Catla catla during chronic sublethal exposure to inorganic arsenic. Chemosphere. 2011;82(7):977-85. DOI: https://doi.org/10.1016/j.chemosphere.2010.10.071
Islam M, Parvin S, Pervin M, Bari A, Khan M. Effects of chronic arsenic toxicity on the haematology and Histoarchitecture of female reproductive system of Black bengal goat. Bangladesh J Vet Med. 2012;9(1):59-66. DOI: https://doi.org/10.3329/bjvm.v9i1.11214
Patra PH, Bandyopadhyay S, Bandyopadhyay MC, Mandal TK. Immunotoxic and genotoxic potential of arsenic and its chemical species in goats. Toxicol Int. 2013;20(1):6-10. DOI: https://doi.org/10.4103/0971-6580.111533
Bisen M, Singh R, Yadav P. Impact of arsenic exposure on erythrocyte morphology and haematological parameters in Labeo rohita. Biochem Cell Arch. 2024;24(1):229-34. DOI: https://doi.org/10.51470/bca.2024.24.1.229
Rana T, Bera AK, Das S. Effect of chronic intake of arsenic-contaminated water on blood oxidative stress indices in cattle in an arsenic-affected zone. Ecotoxicol Environ Saf. 2010;73(6):1327-32. DOI: https://doi.org/10.1016/j.ecoenv.2010.06.002
Kumar A, Ali M, Kumar R. Arsenic exposure in Indo Gangetic plains of Bihar causing increased cancer risk. Sci Rep. 2021;11(1):1-16. DOI: https://doi.org/10.1038/s41598-021-81579-9
Dai L, Lv X, Chen Z. Elevated whole blood arsenic level is associated with type 2 diabetes in coal-burning areas in Guizhou. Toxicol Appl Pharmacol. 2020;403:115135. DOI: https://doi.org/10.1016/j.taap.2020.115135
Hall M, Chen Y, Ahsan H. Blood arsenic as a biomarker of arsenic exposure: Results from a prospective study. Toxicology. 2006;225(2-3):225-33. DOI: https://doi.org/10.1016/j.tox.2006.06.010
Kumar A, Ali M, Raj V. Arsenic causing gallbladder cancer disease in Bihar. Sci Rep. 2023;13(1):1-16. DOI: https://doi.org/10.1038/s41598-023-30898-0
Tan Q, Lv Y, Zhao F. Association of low blood arsenic exposure with level of malondialdehyde among Chinese adults aged 65 and older. Sci Total Environ. 2021;758. DOI: https://doi.org/10.1016/j.scitotenv.2020.143638
Arikan I, Namdar ND, Kahraman C, Dagci M, Ece E. Assessment of Arsenic Levels in Body Samples and Chronic Exposure in People Using Water with a High Concentration of Arsenic: a Field Study in Kutahya. 2015;16:3183-8. DOI: https://doi.org/10.7314/APJCP.2015.16.8.3183
Marciniak W, Matoušek T, Domchek S. Blood arsenic levels as a marker of breast cancer risk among brca1 carriers. Cancers (Basel). 2021;13(13):1-10. DOI: https://doi.org/10.3390/cancers13133345
Kant KK, Lal N. Studies on the remedial effects of coriander and cumin on arsenic exposed Charles Foster Rats. Int J Bioassays. 2016;5(05):4552. DOI: https://doi.org/10.21746/ijbio.2016.05.004
Emediong I, Adele B, Odetola AO, Ige AK, Adewoye EA. Lycopene Reverses Haematological, Oxidative, Hepatic and Renal Damage in Arsenic-Toxic Male Wistar Rats. EC Pharmacol Toxicol. 2019;7:393-403.
Maji C, Biswas S, Sarkar PK. Evaluation of ameliorative effect of two selected plant drugs on experimentally induced arsenic toxicity in sheep. Environ Sci Pollut Res Int. 2020;27(29):36744-53. DOI: https://doi.org/10.1007/s11356-020-09569-4
Kumar V, Akhouri V, Singh SK, Kumar A. Phytoremedial effect of Tinospora cordifolia against arsenic induced toxicity in Charles Foster rats. BioMetals. 2020;33(6):379-96. DOI: https://doi.org/10.1007/s10534-020-00256-y
Akinboro A, Adedosu OT, Badmus JA. Aspalathus Linearis extract ameliorate Haematological disorder, Dyslipidaemia and Tissue toxicity associated with Arsenic exposure in Rats. Phytomedicine Plus. 2022;2(1):100171. DOI: https://doi.org/10.1016/j.phyplu.2021.100171
Parvez F, Lauer FT, Factor-Litvak P. Exposure to arsenic and level of Vitamin D influence the number of Th17 cells and production of IL-17A in human peripheral blood mononuclear cells in adults. PLoS One. 2022;17(4):e0266168. DOI: https://doi.org/10.1371/journal.pone.0266168
Gupta R, Flora SJS. Effect of Centella asiatica on arsenic induced oxidative stress and metal distribution in rats. J Appl Toxicol. 2006;26(3). DOI: https://doi.org/10.1002/jat.1131
Flora SJS, Chouhan S, Kannan GM, Mittal M, Swarnkar H. Combined administration of taurine and monoisoamyl DMSA protects arsenic induced oxidative injury in rats. Oxid Med Cell Longev. 2008;1(1). DOI: https://doi.org/10.4161/oxim.1.1.6481
Zargari F, Ghorbanihaghjo A, Babaei H, Farajnia S, Roodbari NH. Protective effects of hydroalcoholic extract of Nasturtium officinale R.Br (Watercress) on antioxidant status and DNA damage in kidney of rats exposed to sodium arsenite. Adv Environ Biol. 2013;7(14).
Rana T, Bera AK, Das S. Effect of ascorbic acid on blood oxidative stress in experimental chronic arsenicosis in rodents. Food Chem Toxicol. 2010;48(4). DOI: https://doi.org/10.1016/j.fct.2010.01.027
Padmaja B, Madhuri D, Kumar A, Anand AY. Ameliorative efficacy of Emblica officinalis in arsenic induced toxicity in broilers: A haemato-biochemical study. Ind J. 2009;33(1):43-5.
Khan A, Sharaf R, Khan MZ, Saleemi MK, Mahmood F. Arsenic toxicity in broiler chicks and its alleviation with ascorbic acid: A toxico-patho-biochemical study. Int J Agric Biol. 2013;15(6).
Pernis B, Magistretti M. A study of the mechanism of acute hemolytic anemia from arsine. Med Lav. 1960;51.
Chanda S, Dasgupta UB, Guhamazumder D. DNA hypermethylation of promoter of gene p53 and p16 in arsenic-exposed people with and without malignancy. Toxicol Sci. 2006;89(2):431-7. DOI: https://doi.org/10.1093/toxsci/kfj030
Kile ML, Houseman EA, Baccarelli AA. Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014;9(5):774-82. DOI: https://doi.org/10.4161/epi.28153
Lemarie A, Morzadec C, Mérino D, Micheau O, Fardel O, Vernhet L. Arsenic trioxide induces apoptosis of human monocytes during macrophagic differentiation through nuclear factor-kappaB-related survival pathway down-regulation. J Pharmacol Exp Ther. 2006;316(1):304-14. DOI: https://doi.org/10.1124/jpet.105.092874
Morzadec C, Bouezzedine F, Macoch M, Fardel O, Vernhet L. Inorganic arsenic impairs proliferation and cytokine expression in human primary T lymphocytes. Toxicology. 2012;300(1-2):46-56. DOI: https://doi.org/10.1016/j.tox.2012.05.025
Li H, Engström K, Vahter M, Broberg K. Arsenic exposure through drinking water is associated with longer telomeres in peripheral blood. Chem Res Toxicol. 2012;25(11):2333-9. DOI: https://doi.org/10.1021/tx300222t
Mo J, Xia Y, Ning Z, Wade TJ, Mumford JL. Elevated human telomerase reverse transcriptase gene expression in blood cells associated with chronic arsenic exposure in Inner Mongolia, China. Environ Health Perspect. 2009;117(3):354-60. DOI: https://doi.org/10.1289/ehp.11532
Niedzwiecki MM, Liu X, Hall MN. Sex-specific associations of arsenic exposure with global DNA methylation and hydroxymethylation in leukocytes: results from two studies in Bangladesh. Cancer Epidemiol Biomarkers Prev. 2015;24(11):1748-57. DOI: https://doi.org/10.1158/1055-9965.EPI-15-0432
Nandi D, Patra RC, Swarup D. Effect of cysteine, methionine, ascorbic acid and thiamine on arsenic-induced oxidative stress and biochemical alterations in rats. Toxicology. 2005;211(1-2). DOI: https://doi.org/10.1016/j.tox.2005.02.013
Singh S, Rana SVS. Amelioration of arsenic toxicity by L-ascorbic acid in laboratory rat. J Environ Biol. 2007;28(2).
Bhattacharya S, Haldar PK. Ameliorative effect Trichosanthes dioica root against experimentally induced arsenic toxicity in male albino rats. Environ Toxicol Pharmacol. 2012;33(3). DOI: https://doi.org/10.1016/j.etap.2012.02.003
Hossain FMA, Hossain MM, Kabir MG, Fasina FO. Effectiveness of combined treatment using Spirulina and vitamin A against chronic arsenicosis in rats. African J Pharm Pharmacol. 2013;7(20). DOI: https://doi.org/10.5897/AJPP12.008
Prabu SM, Sumedha NC. Ameliorative effect of diallyl trisulphide on arsenic-induced oxidative stress in rat erythrocytes and DNA damage in lymphocytes. J Basic Clin Physiol Pharmacol. 2014;25(2). DOI: https://doi.org/10.1515/jbcpp-2013-0047
Mondal R, Biswas S, Chatterjee A. Protection against arsenic-induced hematological and hepatic anomalies by supplementation of Vitamin C and vitamin e in adult male rats. J Basic Clin Physiol Pharmacol. 2016;27(6):643-52. DOI: https://doi.org/10.1515/jbcpp-2016-0020
Ghosh S, Mishra R, Biswas S, Bhadra RK, Mukhopadhyay PK. α-Lipoic acid mitigates arsenic-induced hematological abnormalities in adult male rats. Iran J Med Sci. 2017;42(3).
Talas ZS, Gulhan MF, Erdogan K, Orun I. Antioxidant effects of propolis on carp Cyprinus carpio exposed to arsenic: Biochemical and histopathologic findings. Dis Aquat Organ. 2014;108(3). DOI: https://doi.org/10.3354/dao02714
Ihsan YNR. Protective Effect of Selenium Against Arsenic-Induced Hematological, Biochemical Alteration, and Organ Development Anomalies in Adult Female Mice. Arch Anesthesiol Crit Care. 2018;4(4):527-34.
Al-Sulivany BSA. The Protective Effects of Blue-Green Algae (Spirulina) Against Arsenic-Induced Differences in Lipid Panel and Hematological Parameters in Female Rats (Rattus norvegicus). Egypt J Vet Sci. 2024;55(3):785-93. DOI: https://doi.org/10.21608/ejvs.2023.245190.1657
Downloads
Published
How to Cite
Issue
Section
