Abstract
Groundwater used for drinking has been contaminated with naturally occurring inorganic arsenic and other metals, and metal-contaminated drinking water is the biggest threat to public health in Bangladesh. Toxic metals present in the drinking water have a strong relationship with chronic diseases in humans. Antimony (Sb), a naturally occurring metal, has been reported to be present in the drinking water along with other heavy metals in Bangladesh. Although Sb is present in the environment, very little attention has been given to the toxic effects of Sb. The present study was designed to investigate the in vivo effects of Sb on neurobehavioral changes like anxiety, learning and memory impairment, and blood indices related to organ dysfunction. Mice exposed to antimony potassium-tartrate hydrate (Sb) (10 mg/kg body weight) significantly (p < 0.05) decreased the time spent in open arms while increased the time spent in closed arms compared to the control mice in elevated plus maze. The mean latency time of control group to find the platform decreased (p < 0.05) significantly during 7 days learning as compared to Sb-treated group in Morris water maze test, and Sb-exposed group spent significantly (p < 0.05) less time in the desired quadrant as compared to the control group in probe trial. Sb treatment also significantly altered blood indices related to liver and kidney dysfunction. Additionally, Sb-induced biochemical alterations were associated with significant perturbations in histological architecture of liver and kidney of Sb-exposed mice. These data suggest that Sb has a toxic effect on neurobehavioral and biochemical changes in mice.
![](https://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12011-018-1290-5/MediaObjects/12011_2018_1290_Fig1_HTML.gif)
![](https://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12011-018-1290-5/MediaObjects/12011_2018_1290_Fig2_HTML.gif)
![](https://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12011-018-1290-5/MediaObjects/12011_2018_1290_Fig3_HTML.gif)
![](https://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12011-018-1290-5/MediaObjects/12011_2018_1290_Fig4_HTML.gif)
![](https://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs12011-018-1290-5/MediaObjects/12011_2018_1290_Fig5_HTML.gif)
Similar content being viewed by others
References
Department of Public health engineering, Government of Republic of Bangladesh. Available at http://www.dphe.gov.bd/index.php
EPA (2004) Arsenic in drinking water: treatment technologies, EPA Office of Groundwater and Drinking Water. Available at http://www.epa.gov
Salem HM, Eweida A, Eweida Farag A (2000) Heavy metals in drinking water and their environmental impact on human health. ICEHM 9:542–556
SOS (2014) Arsenic poisoning in Bangladesh. In: The Daily Sun, 2013. Available at http://www.sos-arsenic.net
Chowdhury MAI, Uddin MT, Ahmed MF, Ali MA, Uddin SM (2006) How does arsenic contamination of groundwater causes severity and health hazard in Bangladesh. J Appl Sciences 6:1275–1286
Tapio S, Grosche B (2006) Arsenic in the aetiology of cancer. Mutation Res 612:215–246
GuhaMazumder DN, Haque R, Ghosh N, De BK, Santra A, Chakraborty D, Smith AH (1998) Arsenic levels in drinking water and the prevalence of skin lesions in West Bengal, India. Int J Epidemiol 27(5):871–877
Parvez F, Chen Y, Maria A, Hussain AI, Hassina M, Dhar R, Geen A, Graziano J, Ahsan H (2006) Prevalence of arsenic exposure from drinking water and awareness of its health risks in a Bangladeshi population; results from a large population-based study. Environ Health Perspect 114(3):355–359
Christina RT, Andrea MA (2014) The effects of arsenic exposure on neurological and cognitive dysfunction in human and rodent studies: a review. Curr Environ Health Rep 1:132–147
Ozone K, Ueno S, Ishizaki M, Hayashi O (2000) Toxicity and oxidative stress induced by organic arsenical diphenylarsinic acid and inorganic arsenicals and their effects on spatial learning ability in mice. J Health Sci 56:517–526
Hei TK, Liu SX, Waldren C (1998) Mutagenicity of arsenic in mammalian cells; role of reactive oxygen species. Proc Natl Acad Sci 95(14):8103–8107
Liu SX, Athar M, Lippai I, Waldren C, Hei TK (2001) Induction of oxyradicals by arsenic: implication for mechanism of genotoxicity. Proc Natl Acad Sci 98(4):1643–1648
Frisbie SH, Ortega R, Maynard DM, Sarkar B (2002) The concentrations of arsenic and other toxic elements in Bangladesh’s drinking water. Environ Health Perspect 110(11):1147–1153
Gebel T (1997) Arsenic and antimony: comparative approach of mechanistic toxicology. Chem Biol Interact 107:131–144
Gebel T (1999b) Arsenic and drinking water contamination. Science 283:1458–1459
Gebel T (2000) Confounding variables in the environmental toxicology of arsenic. Toxicology 144:155–162
McCarty KM, Sen DB, Kile ML, Quamruzzaman K, Rahman M, Mahiuddin G, Christiani DC (2004) Antimony: an unlikely confounder in the relationship between well water arsenic and health outcomes in Bangladesh. Environ Health Persp 112(8):809–812
Smith KS, Huyck HLO (1999) An overview of the abundance, relative mobility, bioavailability, and human toxicity of metals. In: The environmental geochemistry of mineral deposits, (Plumlee GS, Logsdon MJ, Filipek LH, eds). Reviews in economic geology Vol 6A–B. Littleton, CO: Soc Econ Geologists, 29–70
Ramírez-Campos J, Ramos-Peek J, Martínez-Barros M, Zamora-Peralta M, Martínez-Cerrato J (1998) Peripheral neuropathy caused by acute arsenic poisoning. Gac Med Mex 134(2):241–246
Aktar S, Jahan M, Alam S, Mohanto NC, Arefin A, Rahman A, Haque A, Himeno S, Hossain K, Saud ZA (2017) Individual and combined effects of arsenic and lead on behavioral and biochemical changes in mice. Biol Trace Elem Res 177:288–296
Poon R, Chu I, Lecavaliew P, Vallf VE, Foster E, Gupta S, Thomas B (1998) Effects of antimony on rats following 90-day exposure via drinking water. Food and Chem Toxicol 36:21–35
Das AP, Bag S, Sahu R, Dua TK, Sinha MK, Gangopadhyay M, Zaman K, Dewanjee S (2010) Protective effect of Corchorus olitorius leaves on sodium arsenite-induced toxicity in experimental rats. Food Chem Toxicol 48:326–335
Pellow S, Chopin P, File SE, Briley M (1985) Validation of open-closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167
Leret ML, Millan JAS, Antonio MT (2003) Perinatal exposure to lead and cadmium affects anxiety-like behavior. Toxicology 186:125–130
D'Hooge R, De Deyn PP (2001) Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev 36(1):60–90
Noman ASM, Dilruba S, Mohanto NC, Rahman L, Khatun Z, Riad W, Mamun AA, Alam S, Aktar S, Chowdhury S, Saud ZA, Rahman Z, Hossain K (2015) Arsenic-induced histological alterations in various organs of mice. J Cytol Histol 6(3):323
Ali N, Hoque MA, Haque A, Salam KA, Karim MR, Rahman A, Islam K, Saud ZA, Khalek MA, Akhand AA, Hossain M, Mandal A, Karim MR, Miyataka H, Himeno S, Hossain K (2010) Association between arsenic exposure and plasma cholinesterase activity: a population based study in Bangladesh. Environ Health 9:36
Barbier O, Jacquillet G, Tauc M, Cougnon M, Poujeol P (2005) Effect of heavy metals on, and handling by, the kidney. Nephron Physiol 99(4):105–110
Tuot DS, Plantinga LC, Hsu CY, Jordan R, Burrows NR, Hedgeman E, Yee J, Saran R, Powe NR, Centers for Disease Control Chronic Kidney Disease Surveillance Team (2011) Chronic kidney disease awareness among individuals with clinical markers of kidney dysfunction. Clin J Am Soc Nephrol 6(8):1838–1844
Wang JP, Wang SL, Lin Q, Zhang L, Huang D, Nq JC (2009) Association of arsenic and kidney dysfunction in people with diabetes and validation of its effects in rats. Environ Int 35(3):507–511
McCallum RI (1999) Antimony in medical history. The Pentland Press, Edinburgh
Andra SS, Makris KC, Shine JP, Lu C (2012) Co-leaching of brominated compounds and antimony from bottled water. Environ Int 38:45–53
Hansen C, Tsirigotaki A, Bak SA, Pergantis SA, Sturup S, Gammelgaard B, Hansen HR (2010) Elevated antimony concentrations in commercial juices. J Environ Monitor 12:822–824
Gross C, Hen R (2004) The developmental origins of anxiety. Nat Rev Neurosci 5(7):545–552
Weinberger DR (2001) Anxiety at the frontier of molecular medicine. N Engl J Med 344(16):1247–1249
Belzung C, Griebel G (2001) Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav Brain Res 125:141–149
Kahloula K, Slimani M, Aoues A (2009) Behavioural and neurochemical studies of perinatal lead exposed in rat wistar. Eur J Sci Res 35:603–614
Brinkel J, Khan MMH, Kraemer A (2008) A systematic review of arsenic exposure and its social and mental health effects with special reference to Bangladesh. Public Health 6(5):1609–1619
Gandhi DN, Kumar R (2013) Arsenic toxicity and neurobehaviors: a review. Innovat Pharma Pharmacother 1:1–15
Rahman M, Saud ZA, Hossain E, Islam K, Karim MR, Yeasmin T, Nikkon F, Mandal A, Hossain K (2012) Ameliorating effects of Zingiber zerumbet Linn. on sodium arsenite-induced changes of blood indices in experimental mice. Life Sci Med Res 41
Oyeronke AO, Kazeem AA, Babatunde O, Oladimeji T (2007) Interaction and enhancement of the toxic effects of sodium arsenite and lead acetate in wistar rats. Afr J Biomed Res 10:59–65
Groth DH, Stettler LE, Burg JR, Busey WM, Grant GC, Wong L (1986) Carcinogenic effects of antimony trioxide and antimony ore concentrate in rats. J Toxicol Environ Health 18:607–626
Newton PE, Bolte HF, Daly IW, Pillsbury BD, Terrill JB, Drew RT, Ben Dyke R, Sheldon AW, Rubin LF (1994) Subchronic and chronic inhalation toxicity of antimony trioxide in the rat. Fundamental Appl Toxicol 22:561–576
Eisenbach C, Sieg O, Stremmel W, Encke J, Merle U (2007) Diagnostic criteria for acute liver failure due to Wilson disease. World J Gastroenterol 13(11):1711–1714
Kaniaris P, Fassoulaki A, Liarmakopoulou K, Dermitzakis E (1979) Serum cholinesterase levels in patients with cancer. Anesth Analg 58:82–84
Montenegro MF, Ruiz-Espejo F, Campoy FJ, Muñoz-Delgado E, de la Cadena MP, Cabezas-Herrera J, Vidal CJ (2006) Acetyl- and butyrylcholinesterase activities decrease in human colon adenocarcinoma. J Mol Neurosci 30(1–2):51–54
Patlolla AK, Tchounwou PB (2005) Serum acetyl cholinesterase as a biomarker of arsenic induced neurotoxicity in Sprague-Dawley rats. Int J Environ Res Public Health 2(1):80–83
Perrone RD, Madias NE, Levey AS (1992) Serum creatinine as an index of renal function: new insights into old concepts. Clinical Chem 38(10):1933–1953
Dieter MP, Jameson CW, Elwell MR, Lodge JW, Hejtmancik M, Grumbein SL, Ryan M, Peters AC (1991) Comparative toxicity and tissue distribution of antimony potassium tartrate in rats and mice dosed by drinking water or intraperitoneal injection. J Toxicol Environ Health 34:51–82
Otto GF, Maren TH, Brown HW (1947) Blood levels and excretion rates of antimony in persons receiving trivalent and pentavalent antimonials. Am J Hygiene 46(2):193–211
Víctor M, Piñeiro-Carrero E, O Piñeiro (2004) Liver Pediatrics 113(4): 1097–1106
GuhaMazumder DN (2005) Effect of chronic intake of arsenic-contaminated water on liver. Toxicol Appl Pharmacol 206:169–175
Sarkar S, Mukherjee S, Chattopadhyay A, Bhattacharya S (2014) Low dose of arsenic trioxide triggers oxidative stress in zebrafish brain: expression of antioxidant genes. Ecotoxicol Environ Safety 107:1–8
Ding X, Su Q, Jiang M, Xie H, Cong J, Wang J (2013) Arsenic affects on cerebellar development of mice. Toxicol Mech Methods 23:672–677
Acknowledgements
We thank MUSC Center for Global Health for their support.
Funding
This work was supported by grants from the University of Rajshahi, Bangladesh (300(6)-5/52/RABI/BINGAN(1) and the grants from the Ministry of Science and Technology, Government of People’s Republic of Bangladesh (39.009.006.01.00.049.2013-2014/BS/104).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical approval (No: 67/320/IAMEBBC/IBSC) for this study was taken from the Institutional Animal, Medical Ethics, Biosafety and Biosecurity Committee (IAMEBBC), Institute of Biological Sciences, University of Rajshahi, Bangladesh. All animals received human care in compliance with the institutional guidelines.
Conflict of Interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Tanu, T., Anjum, A., Jahan, M. et al. Antimony-Induced Neurobehavioral and Biochemical Perturbations in Mice. Biol Trace Elem Res 186, 199–207 (2018). https://doi.org/10.1007/s12011-018-1290-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12011-018-1290-5