Skip to main content

Advertisement

Log in

Lithium Treatment Aggregates the Adverse Effects on Erythrocytes Subjected to Arsenic Exposure

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The present study was designed to investigate the effects of lithium treatment on red blood cells which were given arsenic exposure. Long-term lithium therapy is being extensively used for the treatment of bipolar disorders. Arsenic is a group I carcinogen and a major toxic pollutant in drinking water that affects millions of people worldwide. Male SD rats were segregated into four groups, viz. normal control, lithium treated, arsenic treated, and lithium + arsenic treated. Lithium was supplemented as lithium carbonate at a dose level of 1.1 g/kg diet for a period of 8 weeks. Arsenic was given in the form of sodium arsenite at a dose level of 100 ppm in drinking water, ad libitum, for the same period. Lysates of red blood cells were used to investigate the effects of lithium and arsenic treatments on anti-oxidant enzymes, reduced glutathione (GSH), and lipid peroxidation (LPO) levels. Various hematological parameters, activities of Na+ K+ ATPase and delta-aminolevulinic acid dehydratase (δ-ALAD) were also assessed. A significant reduction was observed in the activities of antioxidant enzymes, GSH levels, total erythrocyte counts, Na+ K+ ATPase, and ALAD enzyme activities in lysates of red blood cells when exposed either to lithium or arsenic. In addition, a significant increase in the levels of malondialdehyde (MDA), lymphocytes, neutrophils, and total leukocytes was also observed following lithium as well as arsenic treatments. However, when arsenic-treated rats were subjected to lithium treatment, a pronounced alteration was noticed in all the above parameters. Therefore, we conclude that lithium supplementation to the arsenic-treated rats enhances the adverse effects on red blood cells and therefore use of lithium may not be medicated to patients who are vulnerable to arsenic exposure through drinking water. It can also be inferred that adverse effects of lithium therapy may get aggravated in patients thriving in the arsenic-contaminated area.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Kleinman LS, Lowin A, Flood E, Gandhi G, Edgell E, Revicki DA (2003) Costs of bipolar disorder. PharmacoEconomics 21:601–622

    Article  PubMed  Google Scholar 

  2. Lenox RH, Hahn CG (2000) Overview of the mechanism of action of lithium in the brain: fifty-year update. J Clin Psychiatry 61:5–15

    PubMed  CAS  Google Scholar 

  3. Malhotra A, Dhawan DK (2008) Zinc improves antioxidative enzymes in red blood cells and hematology in lithium-treated rats. Nutr Res 28:43–50

    Article  PubMed  CAS  Google Scholar 

  4. Permoda-Osip A, Abramowicz M, Kraszewska A, Suwalska A, Chlopocka-Wozniak M, Rybakowski JK (2016) Kidney, thyroid and other organ functions after 40 years or more of lithium therapy: a case series of five patients. Ther Adv Psychopharmacol 6:277–282

    Article  PubMed  PubMed Central  Google Scholar 

  5. Livingstone C, Rampes H (2006) Lithium: a review of its metabolic adverse effects. J Psychopharmacol 20:347–355

    Article  PubMed  Google Scholar 

  6. WHO- World Health Organization (2016) Ten chemicals of major public health concern. World Health Organization, Geneva

    Google Scholar 

  7. WHO- World Health Organization (2008) Guidelines for drinking-water quality. World Health Organization, Geneva

    Google Scholar 

  8. Bera AK, Rana T, Das S, Bhattacharya D, Bandyopadhyay S, Pan D, De S, Samanta S, Chowdhury AN, Mondal TK, Das SK (2010) Ground water arsenic contamination in West Bengal, India: a risk of sub-clinical toxicity in cattle as evident by correlation between arsenic exposure, excretion and deposition. Toxicol Ind Health 26:709–716

    Article  PubMed  CAS  Google Scholar 

  9. Ebenstein A (2012) The consequences of industrialization: evidence from water pollution and digestive cancers in China. Rev Econ Stat 94:186–201

    Article  Google Scholar 

  10. Mazumder DG, Dasgupta UB (2011) Chronic arsenic toxicity: studies in West Bengal, India. Kaohsiung J Med Sci 27:360–370

    Article  CAS  Google Scholar 

  11. Yu HS, Liao WT, Chai CY (2006) Arsenic carcinogenesis in the skin. J Biomed Sci 13:657–666

    Article  PubMed  CAS  Google Scholar 

  12. Vahter M (2002) Mechanisms of arsenic biotransformation. Toxicology 181:211–217

    Article  PubMed  Google Scholar 

  13. Eskandari MR, Fard JK, Hosseini MJ, Pourahmad J (2012) Glutathione mediated reductive activation and mitochondrial dysfunction play key roles in lithium induced oxidative stress and cytotoxicity in liver. Biometals 25:863–873

    Article  PubMed  CAS  Google Scholar 

  14. Shi H, Shi X, Liu KJ (2004) Oxidative mechanism of arsenic toxicity and carcinogenesis. Mol Cell Biochem 255:67–78

    Article  PubMed  CAS  Google Scholar 

  15. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39(1):44–84

    Article  PubMed  CAS  Google Scholar 

  16. Stocks J, Offerman EL, Modell CB, Dormandy TL (1972) The susceptibility to autoxidation of human red cell lipids in health and disease. Br J Haematol 23:713–724

    Article  PubMed  CAS  Google Scholar 

  17. Chakraborti D, Rahman MM, Murrill M, Das R, Patil SG, Sarkar A, Dadapeer HJ, Yendigeri S, Ahmed R, Das KK (2013) Environmental arsenic contamination and its health effects in a historic gold mining area of the Mangalur greenstone belt of Northeastern Karnataka, India. J Hazard Mater 262:1048–1055

    Article  PubMed  CAS  Google Scholar 

  18. Hossain MA, Rahman MM, Murrill M, Das B, Roy B, Dey S, Maity D, Chakraborti D (2013) Water consumption patterns and factors contributing to water consumption in arsenic affected population of rural West Bengal, India. Sci Total Environ 463:1217–1224

    Article  PubMed  CAS  Google Scholar 

  19. Flora SJ, Bhadauria S, Pant SC, Dhaked RK (2005) Arsenic induced blood and brain oxidative stress and its response to some thiol chelators in rats. Life Sci 77:2324–2337

    Article  PubMed  CAS  Google Scholar 

  20. Picot CI, Trivier JM, Nicole A, Sinet PM, Thevenin M (1992) Age-correlated modifications of copper-zinc superoxide dismutase and glutathione-related enzyme activities in human erythrocytes. Clin Chem 38:66–70

    Google Scholar 

  21. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  22. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  PubMed  CAS  Google Scholar 

  23. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  PubMed  CAS  Google Scholar 

  24. Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    PubMed  CAS  Google Scholar 

  25. Williams CMJ, Arscott ID (1971) Glutathione reductase. Methods Enzymol 17:503–509

    Article  Google Scholar 

  26. Flohé L, Günzler WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114–120

    Article  PubMed  Google Scholar 

  27. Luck H (1974). In: Methods in enzymatic anal. 2 (Edn. Bergmeyer) Academic Press, New York, p 885

  28. Kono Y (1978) Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 186:189–195

    Article  PubMed  CAS  Google Scholar 

  29. Wallach DFH, Kamat VB (1966) Preparation of plasma-membrane fragments from mouse ascites tumor cells. Methods Enzymol 8:164–172

    Article  CAS  Google Scholar 

  30. Fiske CH, Subbarow Y (1925) The colorimetric determination of phosphorus. J Biol Chem 66:375–400

    CAS  Google Scholar 

  31. Helen BB, Siegel AL (1971) Improved method for measurement of delta-aminolevulinic acid dehydratase activity of human erythrocytes. Clin Chem 17:1038–1041

    Google Scholar 

  32. Dacie JV, Lewis SM (1991) Practical hematology, 6th edn. Churchill, London

    Google Scholar 

  33. Osredkar J, Sustar N (2011) Copper and zinc, biological role and significance of copper/zinc imbalance. J Clin Toxicol S3:001

    Article  Google Scholar 

  34. Sidhu P, Garg ML, Dhawan DK (2004) Protective effects of zinc on oxidative stress enzymes in liver of protein deficient rats. Nutr Hosp 19(6):341–347

    PubMed  CAS  Google Scholar 

  35. Naja GM, Volesky B (2009) Toxicity and sources of Pb, Cd, Hg, Cr, As, and radionuclides in the environment. Heavy metals in the environment pp13–61

  36. Lu Y, Song S, Wang R, Liu Z, Meng J, Sweetman AJ, Jenkins A, Ferrier RC, Li H, Luo W, Wang T (2015) Impacts of soil and water pollution on food safety and health risks in China. Environ Int 77:5–15

    Article  PubMed  CAS  Google Scholar 

  37. Marafante E, Vahter M, Envall J (1985) The role of the methylation in the detoxication of arsenate in the rabbit. Chem Biol Interact 56:225–238

    Article  PubMed  CAS  Google Scholar 

  38. Trautner EM, Morris R, Noack CH, Gershon S (1955) The excretion and retention of ingested lithium and its effect on the ionic balance of man. Med J Aust 42:280–291

    PubMed  CAS  Google Scholar 

  39. Grim JM, Semones MC, Kuhn DE, Kriska T, Keszler A, Crockett EL (2014) Products of lipid peroxidation, but not membrane susceptibility to oxidative damage, are conserved in skeletal muscle following temperature acclimation. Am J Phys Regul Integr Comp Phys 308(5):439–448

    Google Scholar 

  40. Gutteridge JM, Halliwell B (2000) Free radicals and antioxidants in the year 2000: a historical look to the future. Ann N Y Acad Sci 899:136–147

    Article  PubMed  CAS  Google Scholar 

  41. Kühn H, Borchert A (2002) Regulation of enzymatic lipid peroxidation: the interplay of peroxidizing and peroxide reducing enzymes. Free Radic Biol Med 33(2):154–172

    Article  PubMed  Google Scholar 

  42. Niki E (2009) Lipid peroxidation: physiological levels and dual biological effects. Free Radic Biol Med 47(5):469–484

    Article  PubMed  CAS  Google Scholar 

  43. Barrera G (2012) Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol 2012:137289

    PubMed  PubMed Central  Google Scholar 

  44. Anderson PM, Desnick RJ (1979) Purification and properties of delta-aminolevulinate dehydrase from human erythrocytes. J Biol Chem 254:6924–6930

    PubMed  CAS  Google Scholar 

  45. Jarret C, Stauffer F, Henz ME, Marty M, Luond RM, Bobalova J, Schurmann P, Neier R (2000) Inhibition of Escherichia coli porphobilinogen synthase using analogs of postulated intermediates. Chem Biol 7:185–196

    Article  PubMed  CAS  Google Scholar 

  46. Leelakunakorn W, Sriwworawit R, Soontaros S (2005) Ceruloplasmin oxidase activity as a biomarker of lead exposure. J Occup Health 57:56–60

    Article  Google Scholar 

  47. Flora SJS, Pant BP, Tripathi N, Kannan JM, Jaiswal DK (1997) Therapeutic efficacy of a few diesters of meso 2,3-dimercaptosuccinic acid during sub-chronic arsenic intoxication in rats. J Occup Health 39:119–123

    Article  CAS  Google Scholar 

  48. Lakshmi G (1989) Effect of lithium on regulation of two molecular forms of Na + K+ ATPase in rat brain. Ind J Exp Biol 27:903–906

    CAS  Google Scholar 

  49. Guerri C, Ribelles M, Grisolia S (1980) Effects of lithium and alcohol administration on Na + K+ ATPase activity. Biochem Pharmacol 30:25–30

    Article  Google Scholar 

  50. Banerjee U, Dasgupta A, Rout JK, Singh OP (2012) Effects of lithium therapy on Na+–K+-ATPase activity and lipid peroxidation in bipolar disorder. Prog Neuro-Psychopharmacol Biol Psychiatry 37(1):56–61

    Article  CAS  Google Scholar 

  51. Yoshino Y, Yuan B, Miyashita SI, Iriyama N, Horikoshi A, Shikino O, Toyoda H, Kaise T (2009) Speciation of arsenic trioxide metabolites in blood cells and plasma of a patient with acute promyelocytic leukemia. Anal Bioanal Chem 393:689–697

    Article  PubMed  CAS  Google Scholar 

  52. Ratey JJ, Mallinger AG (1977) The relationship between extra-and intracellular lithium concentration in human red blood cells: an in vitro study. Br J Psychiatry 131(1):59–62

    Article  PubMed  CAS  Google Scholar 

  53. Lu M, Wang H, Li XF, Lu X, Cullen WR, Arnold LL, Cohen SM, Le XC (2004) Evidence of hemoglobin binding to arsenic as a basis for the accumulation of arsenic in rat blood. Chem Res Toxicol 17(12):1733–1742

    Article  PubMed  CAS  Google Scholar 

  54. Sharma SD, Iqbal M (2005) Lithium induced toxicity in rats: a hematological, biochemical and histopathological study. Biol Pharm Bull 28(5):834–837

    Article  PubMed  CAS  Google Scholar 

  55. Ozdemir MA, Sofuoghi S, Tamrikilu G, Aldanmaz F, Esel E, Dunbar S (1994) Lithium-induced hematological changes in patients with bipolar affective disorder. Biol Psychiatry 35:210–213

    Article  PubMed  CAS  Google Scholar 

  56. McGrath HE, Wade PM, Kister VK, Quesenberry PJ (1991) Lithium stimulation of HPP-CFC and stromal growth factor production in murine dexter culture. J Cell Physiol 151(2):276–286

    Article  Google Scholar 

  57. Dwivedi N, Flora SJ (2011) Concomitant exposure to arsenic and organophosphates on tissue oxidative stress in rats. Food Chem Toxicol 49(5):1152–1159

    Article  PubMed  CAS  Google Scholar 

  58. Jalaludeen AM, Ha WT, Lee R, Kim JH, Do JT, Park C, Heo YT, Lee WY, Song H (2016) Biochanin A ameliorates arsenic-induced hepato-and hematotoxicity in rats. Molecules 21(1):69–73

    Article  PubMed  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the Department of Biophysics, Panjab University, Chandigarh, for providing the necessary facilities to carry out the various experimental procedures for this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Devinder Kumar Dhawan.

Ethics declarations

The animals were maintained according to the guidelines approved by the University’s Animal Ethical Committee and were housed in polypropylene cages under good hygienic conditions.

Conflict of Interest

None to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bhardwaj, P., Jain, K. & Dhawan, D.K. Lithium Treatment Aggregates the Adverse Effects on Erythrocytes Subjected to Arsenic Exposure. Biol Trace Elem Res 184, 206–213 (2018). https://doi.org/10.1007/s12011-017-1168-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-017-1168-y

Keywords

Navigation