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Inhibitory Effects of Selenium on Arsenic-Induced Anxiety-/Depression-Like Behavior and Memory Impairment

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Abstract

Elevated arsenic (As) contamination in drinking water was detected in many areas of Pakistan. The intoxication of As causes various neurological diseases in humans, which can be inhibited by the administration of potent antioxidants. Trace elements are also found in drinking water such as selenium (Se), which possess antioxidant potential. The main purpose of the current study is to find out the protective effect of Se against As toxicity which can cause anxiety- and depression-like behaviors as well as memory impairment. Thirty-six male rats were divided into six groups: (1) distilled water (dw)+dw, (2) dw+Se (0.175 mg/ml/kg), (3) dw+Se (0.35mg/ml/kg), (4) dw+As (2.5mg/ml/kg), (5) As (2.5mg/ml/kg) + Se (0.175 mg/ml/kg), and (6) As (2.5mg/ml/kg) + Se (0.35 mg/ml/kg). Rats were treated with respective treatment for 4 weeks. Sub-chronic treatment of As reduced time spent in open arm (elevated plus maze), and lightbox (light-dark activity test) and increased immobility time in forced swim test indicate anxiety- and/or depression-like behavior, respectively. Conversely, rats treated with As+Se (at both doses) increased time spent in open arm (elevated plus maze), and lightbox (light-dark activity test) and decreased immobility time in forced swim test indicate the anxiolytic and anti-depressive effect of Se, respectively. Co-administration of Se (0.175 and 0.35) inhibited As instigated reduction of spatial memory performed in Morris water maze. The reversal in the reduced level of malondialdehyde and activity of acetylcholinesterase in the hippocampus by Se was observed in As-treated animals, while the activity of antioxidant enzymes in the hippocampus was increased in As+Se than dw+As-treated animals. Histopathological studies have shown the reversal of hippocampus deterioration by Se in As-treated rats. The results may imply to prevent the intoxication of As instigated impairment in behavioral and biochemical indices by Se supplementation and/or increased safer intake.

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Data Availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Medina-Pizzali ML, Robles P, Mendoza M et al (2017) Arsenic intake: impact in human nutrition and health. Rev Peru Med Exp Salud Publica 35(1):93–102

    Article  Google Scholar 

  2. Drzewiecka K, Gąsecka M, Rutkowski P, Magdziak Z, Goliński P, Mleczek M (2018) Arsenic forms and their combinations induce differences in phenolic accumulation in Ulmus laevis Pall. J Plant Physiol 220:34–42

    Article  CAS  PubMed  Google Scholar 

  3. Sodhi KK, Kumar M, Agrawal PK, Singh DK (2019) Perspectives on arsenic toxicity, carcinogenicity and its systemic remediation strategies. Environ Technol Innov 16:100462

    Article  Google Scholar 

  4. Karcioglu O, Satar S, Yilmaz E et al (2019) A Long-Lasting, “Emergency”: Arsenic Poisoning in the Developing World. World J Surg Surgical Res 2:1122

    Google Scholar 

  5. Liu T, Zhong S, Liao X, Chen J, He T, Lai S, Jia Y (2015) A meta-analysis of oxidative stress markers in depression. PLoS One 10(10):e0138904

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Rana MN, Tangpong J, Rahman MM (2018) Toxicodynamics of lead, cadmium, mercury and arsenic-induced kidney toxicity and treatment strategy: a mini review. Toxicol Rep 5:704–713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Souri Z, Karimi N, de Oliveira LM (2018) Antioxidant enzymes responses in shoots of arsenic hyperaccumulator, Isatis cappadocica Desv., under interaction of arsenate and phosphate. Environ Technol 39(10):1316–1327

    Article  CAS  PubMed  Google Scholar 

  8. Soni M, Prakash C, Dabur R, Kumar V (2018) Protective effect of hydroxytyrosol against oxidative stress mediated by arsenic-induced neurotoxicity in rats. Appl Biochem Biotechnol 186(1):27–39

    Article  CAS  PubMed  Google Scholar 

  9. Umeno A, Biju V, Yoshida Y (2017) In vivo ROS production and use of oxidative stress-derived biomarkers to detect the onset of diseases such as Alzheimer’s disease, Parkinson’s disease, and diabetes. Free Radic Res 51:413–427

    Article  CAS  PubMed  Google Scholar 

  10. Nurchi VM, Djordjevic AB, Crisponi G et al (2020) Arsenic toxicity: molecular targets and therapeutic agents. Biomolecules 10(2):235

    Article  CAS  PubMed Central  Google Scholar 

  11. Jomova K, Jenisova Z, Feszterova M, Baros S, Liska J, Hudecova D, Rhodes CJ, Valko M (2011) Arsenic: toxicity, oxidative stress and human disease. J Appl Toxicol 31(2):95–107

    CAS  PubMed  Google Scholar 

  12. Yu NH, Pei H, Huang YP, Li YF (2017) Epigallocatechin-3-gallate inhibits arsenic-induced inflammation and apoptosis through suppression of oxidative stress in mice. Cell Physiol Biochem 41(5):1788–1800

    Article  CAS  PubMed  Google Scholar 

  13. Samad N, Jabeen S, Imran I, Zulfiqar I, Bilal K (2019) Protective effect of gallic acid against arsenic-induced anxiety−/depression-like behaviors and memory impairment in male rats. Metab Brain Dis 34(4):1091–1102

    Article  CAS  PubMed  Google Scholar 

  14. Chandravanshi LP, Patel DK (2017) Subchronic early life arsenic exposure at low doses impaired the biogenic amine neurotransmitter and nitric oxide levels in different brain regions of rats. J Environ Anal Toxicol 7(4):4

    Article  Google Scholar 

  15. Kiełczykowska M, Kocot J, Paździor M, Musik I (2018) Selenium - a fascinating antioxidant of protective properties. Adv Clin Exp Med 27(2):245–255

    Article  PubMed  Google Scholar 

  16. Wang N, Tan HY, Li S et al (2017) Supplementation of micronutrient selenium in metabolic diseases: Its role as an antioxidant. Oxidative Med Cell Longev 2017:7478523

    Google Scholar 

  17. Ighodaro OM, Akinloye OA (2018) First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J Med 54(4):287–293

    Article  Google Scholar 

  18. Islam MT (2017) Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res 39:73–82

    Article  CAS  PubMed  Google Scholar 

  19. Amani H, Habibey R, Shokri F, Hajmiresmail SJ, Akhavan O, Mashaghi A, Pazoki-Toroudi H (2019) Selenium nanoparticles for targeted stroke therapy through modulation of inflammatory and metabolic signaling. Sci Rep 9(1):6044

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Wang J, Liu Z, He X, Lian S, Liang J, Yu D, Sun D, Wu R (2018) Selenium deficiency induces duodenal villi cell apoptosis via an oxidative stress-induced mitochondrial apoptosis pathway and an inflammatory signaling-induced death receptor pathway. Metallomics 10(10):1390–1400

    Article  CAS  PubMed  Google Scholar 

  21. Wang H, Bi C, Wang Y, Sun J, Meng X, Li J (2018) Selenium ameliorates Staphylococcus aureus-induced inflammation in bovine mammary epithelial cells by inhibiting activation of TLR2, NF-κB and MAPK signaling pathways. BMC Vet Res 14(1):197

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Ellwanger JH, Franke SI, Bordin DL et al (2016) Biological functions of selenium and its potential influence on Parkinson’s disease. An Acad Bras Cienc 88(3 Suppl):1655–1674

    Article  CAS  PubMed  Google Scholar 

  23. Sanmartin C, Plano D, Font M, Palop JA (2011) Selenium and clinical trials: new therapeutic evidence for multiple diseases. Curr Med Chem 18(30):4635–4650

    Article  CAS  PubMed  Google Scholar 

  24. Van der Jeugd A, Parra-Damas A, Baeta-Corral R et al (2018) Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice. Sci Rep 8(1):6431

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Bocarsly ME, Barson JR, Hauca JM, Hoebel BG, Leibowitz SF, Avena NM (2012) Effects of perinatal exposure to palatable diets on body weight and sensitivity to drugs of abuse in rats. Physiol Behav 107:568–575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Samad N, Ali A, Yasmin F, Ullah R, Bari A (2020) Behavioral and biochemical effects of Mukia madrespatana following single immobilization stress on rats. Medicina (Kaunas) 56(7):350

    Article  Google Scholar 

  27. Madiha S, Haider S (2019) Curcumin restores rotenone induced depressive-like symptoms in animal model of neurotoxicity: assessment by social interaction test and sucrose preference test. Metab Brain Dis 34:297–308

    Article  CAS  PubMed  Google Scholar 

  28. Samad N, Saleem A (2018) Administration of Allium cepa L. bulb attenuates stress-produced anxiety and depression and improves memory in male mice. Metab Brain Dis 33:271–281

    Article  CAS  PubMed  Google Scholar 

  29. Samad N, Saleem A, Yasmin F, Shehzad MA (2018) Quercetin protects against stress-induced anxiety- and depression-like behavior and improves memory in male mice. Physiol Res 67:795–808

    Article  CAS  PubMed  Google Scholar 

  30. Porsolt RD (1981) Behavioral despair. In: Enna SJ, Malick JB, Richelson E (eds) Antidepressants: neurochemical, behavioral and clinical perspectives. Raven Press, New York, pp 121–139

    Google Scholar 

  31. Chow CK, Tappel AL (1972) An enzymatic protective mechanism against lipid peroxidation damage to lungs of ozone-exposed rats. Lipids 7:518–524

    Article  CAS  PubMed  Google Scholar 

  32. Naskar S, Islam A, Mazumder UK et al (2011) In vitro and in vivo antioxidant potential of hydromethanolic extract of phoenix dactylifera fruits. J Sci Res 2:144–157

    Article  CAS  Google Scholar 

  33. Pari L, Latha M (2001) Protective role of Scorparia dulcis plant extract on brain antioxidant status and lipid peroxidation in STZ diabetic male Wistar rats. BMC Complement Altern Med 6:16

    Google Scholar 

  34. Flohe L, Gunzler WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114–121

    Article  CAS  PubMed  Google Scholar 

  35. Ellman GL, Courtney KD, Andres V et al (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  CAS  PubMed  Google Scholar 

  36. Thenmozhi AJ, Raja TR, Janakiraman U et al (2015) Neuroprotective effect of hesperidin on aluminum chloride induced Alzheimer’s disease in Wistar rats. Neurochem Res 40:767–776

    Article  CAS  Google Scholar 

  37. Bühl V, Álvarez MC, Torre MH, Pistón M, Mañay N (2017) Biomonitoring of arsenic in wood workers exposed to CCA and evaluation of other non-occupational sources in Uruguay. Int J Occup Environ Health 23(1):71–80

    Article  PubMed  CAS  Google Scholar 

  38. Sen D, Biswas PS (2012) Arsenicosis: is it a protective or predisposing factor for mental illness? Iran J Psychiatry 7(4):180–183

    PubMed  PubMed Central  Google Scholar 

  39. Maheshwari N, Khan FH, Mahmood R (2018) 3,4-Dihydroxybenzaldehyde lowers ROS generation and protects human red blood cells from arsenic(III) induced oxidative damage. Environ Toxicol 33(8):861–875

    Article  CAS  Google Scholar 

  40. Samad N, Batool F, Haleem DJ (2007) Neurochemical and behavioral effects of 8-OH-DPAT following exposure to restraint stress in rats. Pharmacol Rep 59(2):173–180

    CAS  PubMed  Google Scholar 

  41. Szopa A, Poleszak E, Bogatko K, Wyska E, Wośko S, Doboszewska U, Świąder K, Wlaź A, Dudka J, Wróbel A, Wlaź P, Serefko A (2018) DPCPX, a selective adenosine A1 receptor antagonist, enhances the antidepressant-like effects of imipramine, escitalopram, and reboxetine in mice behavioral tests. Naunyn Schmiedeberg's Arch Pharmacol 391(12):1361–1371

    Article  CAS  Google Scholar 

  42. Samad N, Perveen T, Haider S, Haleem M, Haleem DJ (2006) Inhibition of restraint-induced neuroendocrine and serotonergic responses by buspirone in rats. Pharmacol Rep 58(5):636–642

    CAS  PubMed  Google Scholar 

  43. Fraga DB, Olescowicz G, Moretti M et al (2018) Anxiolytic effects of ascorbic acid and ketamine in mice. J Psychiatr Res 100:16–23

    Article  PubMed  Google Scholar 

  44. Kędzierska E, Dudka J, Poleszak E, Kotlińska JH (2017) Antidepressant and anxiolytic-like activity of sodium selenite after acute treatment in mice. Pharmacol Rep 69(2):276–280

    Article  PubMed  CAS  Google Scholar 

  45. Ingawale DK, Mandlik SK, Naik SR (2014) Models of hepatotoxicity and the underlying cellular, biochemical and immunological mechanism(s): a critical discussion. Environ Toxicol Pharmacol 37:118–133

    Article  CAS  PubMed  Google Scholar 

  46. Manna P, Sinha M, Sil PC (2008) Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid. Arch Toxicol 82(3):137–149

    Article  CAS  PubMed  Google Scholar 

  47. Całyniuk B, Grochowska-Niedworok E, Walkiewicz K, Kawecka S, Popiołek E, Fatyga E (2016) Malondialdehyde (MDA) -product of lipid peroxidation as marker of homeostasis disorders and aging. Ann Acad Med Silesiensis 70(4):224–228

    Article  CAS  Google Scholar 

  48. Flora SJS (1999) Arsenic-induced oxidative stress and its reversibility following combined administration of N-acetylcysteine and meso 2,3-dimercaptosuccinic acid in rats. Clin Exp Pharmacol Physiol 26(11):865–869

    Article  CAS  PubMed  Google Scholar 

  49. Isuzugawa K, Inoue M, Ogihara Y (2001) Catalase contents in cells determine sensitivity to the apoptosis inducer gallic acid. Biol Pharm Bull 24(9):1022–1026

    Article  CAS  PubMed  Google Scholar 

  50. McCord JM, Keele BB, Fridovich I (1976) An enzyme-based theory of obligate anaerobis: the physiological functions of superoxide dismutase. Proc Natl Acad Sci U S A 68(5):1024–1031

    Article  Google Scholar 

  51. Gutteridge JMC (1995) Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 41(12 Pt 2):1819–1828

    Article  CAS  PubMed  Google Scholar 

  52. Zimmerman MT, Bayse CA, Ramoutar RR, Brumaghim JL (2015) Sulfur and selenium antioxidants: challenging radical scavenging mechanisms and developing structure-activity relationships based on metal binding. J Inorg Biochem 145:30–40

    Article  CAS  PubMed  Google Scholar 

  53. Khan AZ, Khan IU, Khan S, Afzal S, Hamid M, Tariq M, Haq I, Ullah N, Khan M, Bilal S, Huwang K, Liu R (2019) Selenium-enriched probiotics improve hepatic protection by regulating pro-inflammatory cytokines and antioxidant capacity in broilers under heat stress conditions. J Adv Vet Anim Res 6(3):355–361

    Article  PubMed  PubMed Central  Google Scholar 

  54. Jin Y, Coad J, Pond R, Kim N, Brough L (2020) Selenium intake and status of postpartum women and postnatal depression during the first year after childbirth in New Zealand - Mother and Infant Nutrition Investigation (MINI) study. J Trace Elem Med Biol 61:126503

    Article  CAS  PubMed  Google Scholar 

  55. Rodríguez-Gutiérrez G, Rubio-Senent F, Gómez-Carretero A, Maya I, Fernández-Bolaños J, Duthie GG, de Roos B (2019) Selenium and sulphur derivatives of hydroxytyrosol: inhibition of lipid peroxidation in liver microsomes of vitamin E-deficient rats. Eur J Nutr 58(5):1847–1851

    Article  PubMed  CAS  Google Scholar 

  56. Hu L, Fan H, Wu D, Liao Y, Shen F, Liu W, Huang R, Zhang B, Wang X (2020) Effects of selenium on antioxidant enzyme activity and bioaccessibility of arsenic in arsenic-stressed radish. Ecotoxicol Environ Saf 200:110768

    Article  CAS  PubMed  Google Scholar 

  57. Blake MG, Boccia MM (2018) Basal forebrain cholinergic system and memory. Curr Top Behav Neurosci 37:253–273

    Article  CAS  PubMed  Google Scholar 

  58. Haam J, Yakel JL (2017) Cholinergic modulation of the hippocampal region and memory function. J Neurochem 142 Suppl 2(Suppl 2):111–121

    Article  PubMed  CAS  Google Scholar 

  59. Emad S, Qadeer S, Sadaf S, Batool Z, Haider S, Perveen T (2017) Attenuation of stress induced memory deficits by nonsteroidal anti-inflammatory drugs (NSAIDs) in rats: role of antioxidant enzymes. Pharmacol Rep 69(2):300–305

    Article  CAS  PubMed  Google Scholar 

  60. Kaufer D, Friedman A, Seidman S, Soreq H (1998) Acute stress facilitates long-lasting changes in cholinergic gene expression. Nature 393(6683):373–377

    Article  CAS  PubMed  Google Scholar 

  61. Biswas S, Anjum A, Banna HU, Rahman M, Siddique AE, Karim Y, Nikkon F, Haque A, Hossain K, Saud ZA (2019) Manganese attenuates the effects of arsenic on neurobehavioral and biochemical changes in mice co-exposed to arsenic and manganese. Environ Sci Pollut Res Int 26(28):29257–29266

    Article  CAS  PubMed  Google Scholar 

  62. Kumar MR, Reddy GR (2018) Influence of age on arsenic-induced behavioral and cholinergic perturbations: amelioration with zinc and α-tocopherol. Hum Exp Toxicol 37(3):295–308

    Article  CAS  PubMed  Google Scholar 

  63. Babür E, Tan B, Yousef M et al (2019) Deficiency but not supplementation of selenium impairs the hippocampal long-term potentiation and hippocampus-dependent learning. Biol Trace Elem Res 192(2):252–262

    Article  PubMed  CAS  Google Scholar 

  64. Ma KG, Lv J, Yang WN, Chang KW, Hu XD, Shi LL, Zhai WY, Zong HF, Qian YH (2018) The p38 mitogen activated protein kinase regulates β amyloid protein internalization through the α7 nicotinic acetylcholine receptor in mouse brain. Brain Res Bull 137:41–52

    Article  CAS  PubMed  Google Scholar 

  65. Yadav M, Jindal DK, Dhingra MS, Kumar A, Parle M, Dhingra S (2018) Protective effect of gallic acid in experimental model of ketamine induced psychosis: possible behavior, biochemical, neurochemical and cellular alterations. Inflammopharmacology 26(2):413–424

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Bahauddin Zakariya University, Multan, Pakistan, for their support.

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Correspondence to Noreen Samad.

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Samad, N., Rao, T., Rehman, M.H.u. et al. Inhibitory Effects of Selenium on Arsenic-Induced Anxiety-/Depression-Like Behavior and Memory Impairment. Biol Trace Elem Res 200, 689–698 (2022). https://doi.org/10.1007/s12011-021-02679-1

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