Skip to main content

Advertisement

SpringerLink
Log in

Effect of Zinc on Hepatic and Renal Tissues of Chronically Arsenic Exposed Rats: A Biochemical and Histopathological Study

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

Abstract

Consumption of arsenic-contaminated drinking water has become major global health concern. One of the major mechanism responsible for the toxicity of arsenicals is the generation of oxidative stress. Zinc, a nutritional antioxidant, plays key role in maintaining various cellular pathways. The present study was aimed at elucidating the effects of zinc supplementation on hepatic and renal tissue damage caused by arsenic exposure to rats. Rats were randomly divided into four experimental groups: control; As administered; Zn supplemented; combined zinc; and arsenic supplemented. Arsenic exposure resulted in significantly elevated accumulation of arsenic in the liver and kidney tissue. In the liver, exposure to arsenic reduced the levels of reduced glutathione (GSH), total glutathione (TG), redox ratio, and the activity of superoxide dismutase (SOD), whereas lipid peroxidation (LPO), inflammation markers, and nitric oxide (NO) levels were elevated with no significant change in catalase (CAT) activity. Arsenic exposure also enhanced the serum levels of liver functional indices and histological abnormalities in liver sections. In the kidney, a significant increase in NO levels and decrease in SOD activity was observed, with no significant changes in the rest of the parameters. The administration of zinc- to arsenic-intoxicated animals significantly improved their hepatic function parameters, arsenic burden, and histological changes which were associated with the restoration of enzymatic and non-enzymatic antioxidant defense system as compared to their intoxicated counterparts. In the kidney also, the NO levels and SOD activity were restored. This data reveals that zinc is effective in ameliorating the toxic effects inflicted by chronic arsenic toxicity.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data Availability

The data of the paper are available upon request from the corresponding author.

References

  1. Huang L, Wu H, van-der Kuijp TJ (2015) The health effects of exposure to arsenic-contaminated drinking water: a review by global geographical distribution. Int J Environ Health Res 25(4):432–452. https://doi.org/10.1080/09603123.2014.958139

    Article  CAS  PubMed  Google Scholar 

  2. Singh SK, Stern EA (2017) Global arsenic contamination: living with the poison nectar. Environment 59(2):24–28. https://doi.org/10.1080/00139157.2017.1274583

    Article  Google Scholar 

  3. Barringer JL, Reilly PA (2013) Arsenic in groundwater: a summary of sources and the biogeochemical and hydrogeologic factors affecting arsenic occurrence and mobility. In: Current perspectives in contaminant hydrology and water resources sustainability IntechOpen. https://doi.org/10.5772/55354

  4. Chatterjee M (2014) Arsenic in groundwater impacts 7 crore lives: panel. Times of India. Accessed 12 December 2014

  5. Sarma SD, Hussain A, Sarma JD (2017) Advances made in understanding the effects of arsenic exposure on humans. Curr Sci 112:2008–2015. https://doi.org/10.18520/cs/v112/i10/2008-2015

    Article  CAS  Google Scholar 

  6. Del-Razo LM, Quintanilla-Vega B, Brambila-Colombres E, Calderón-Aranda ES, Manno M, Albores A (2001) Stress proteins induced by arsenic. Toxicol Appl Pharmacol 177:132–148. https://doi.org/10.1006/taap.2001.9291

    Article  CAS  PubMed  Google Scholar 

  7. Zollner H (1963) Handbook of enzyme inhibitors. VCH, New York, p 1065

    Google Scholar 

  8. Shen S, Li XF, Cullen WR, Weinfeld M, Chris Le X (2013) Arsenic binding to proteins. Chem Rev 113:7769–7792. https://doi.org/10.1021/cr300015c

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Flora SJS (2011) Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 51:257–281. https://doi.org/10.1016/j.freeradbiomed.2011.04.008

    Article  CAS  PubMed  Google Scholar 

  10. Bergquist ER, Fischer RJ, Sugden KD, Martin BD (2009) Inhibition by methylated organo-arsenicals of the respiratory 2-oxo-acid dehydrogenases. J Organomet Chem 694:973–980. https://doi.org/10.1016/j.jorganchem.2008.12.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tchounwou PB, Yedjou CG, Udensi UK, Pacurari M, Stevens JJ, Patlolla AK, Noubissi F, Kumar S (2019 Feb) State of the science review of the health effects of inorganic arsenic: perspectives for future research. Environ Toxicol 34(2):188–202

    Article  CAS  Google Scholar 

  12. Radi R (2018) Oxygen radicals, nitric oxide, and peroxynitrite: redox pathways in molecular medicine. Proc Natl Acad Sci U S A 115(23):5839–5848. https://doi.org/10.1073/pnas.1804932115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Pace C, Dagda R, Angermann J (2017) Antioxidants protect against arsenic induced mitochondrial cardio-toxicity. Toxics 5(4):38. https://doi.org/10.3390/toxics5040038

    Article  CAS  PubMed Central  Google Scholar 

  14. Andreini C, Banci L, Bertini I, Rosato A (2006) Counting the zinc-proteins encoded in the human genome. J Proteome Res 5(1):196–201. https://doi.org/10.1021/pr050361j

    Article  CAS  PubMed  Google Scholar 

  15. Cruz JBF, Soares HF (2011) Uma revisão sobre o zinco. Ensaios Ciência Ciências Biológicas Agrárias Saúde 15(1):207–222

    Google Scholar 

  16. Bell SG, Vallee BL (2009) The metallothionein/thionein system: an oxidoreductive metabolic zinc link. Chembiochem 10(1):55–62. https://doi.org/10.1002/cbic.200800511

    Article  CAS  PubMed  Google Scholar 

  17. Modi M, Kaul RK, Kannan GM, Flora SJ (2006) Co-administration of zinc and n-acetylcysteine prevents arsenic-induced tissue oxidative stress in male rats. J Trace Elem Med Biol 20(3):197–204. https://doi.org/10.1016/j.jtemb.2006.02.002

    Article  CAS  PubMed  Google Scholar 

  18. Modi M, Pathak U, Kalia K, Flora SJS (2005) Arsenic antagonism studies with monoisoamyl DMSA and zinc in male mice. Environ Toxicol Pharmacol 19(1):131–138. https://doi.org/10.1016/j.etap.2004.05.008

    Article  CAS  PubMed  Google Scholar 

  19. Kumar A, Malhotra A, Nair P, Garg ML, Dhawan DK (2010) Protective role of zinc in ameliorating arsenic-induced oxidative stress and histological changes in rat liver. J Environ Pathol Toxicol Oncol 29(2):91–100. https://doi.org/10.1615/jenvironpatholtoxicoloncol.v29.i2.30

    Article  CAS  PubMed  Google Scholar 

  20. Ganger R, Garla R, Mohanty BP, Bansal MP, Garg ML (2016) Protective effects of zinc against acute arsenic toxicity by regulating antioxidant defense system and cumulative metallothionein expression. Biol Trace Elem Res 169(2):218–229. https://doi.org/10.1007/s12011-015-0400-x

    Article  CAS  PubMed  Google Scholar 

  21. Mershiba SD, Dassprakash MV, Saraswathy SD (2013) Protective effect of naringenin on hepatic and renal dysfunction and oxidative stress in arsenic intoxicated rats. Mol Biol Rep 40(5):3681–3691. https://doi.org/10.1007/s11033-012-2444-8

    Article  CAS  PubMed  Google Scholar 

  22. Flora SJ (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. https://doi.org/10.1046/j.1440-1681.1999.03157.x

    Article  CAS  PubMed  Google Scholar 

  23. Pi J, Horiguchi S, Sun Y, Nikaido M, Shimojo N, Hayashi T, Yamauchi H, Itoh K, Yamamoto M, Sun G, Waalkes MP (2003) A potential mechanism for the impairment of nitric oxide formation caused by prolonged oral exposure to arsenate in rabbits. Free Radic Biol Med 35(1):102–113. https://doi.org/10.1016/S0891-5849(03)00269-7

    Article  CAS  PubMed  Google Scholar 

  24. Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22(3):659–661. https://doi.org/10.1096/fj.07-9574LSF

    Article  CAS  PubMed  Google Scholar 

  25. Sengupta P (2013) The laboratory rat: relating its age with human’s. Int J Prev Med 4(6):624–630

    PubMed  PubMed Central  Google Scholar 

  26. Wills E (1966) Mechanisms of lipid peroxide formation in animal tissues. Biochem J 99(3):667–676. https://doi.org/10.1042/bj0990667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Raddassi K, Berthon B, Petit JF, Lemaire G (1994) Role of calcium in the activation of mouse peritoneal macrophages: induction of NO synthase by calcium ionophores and thapsigargin. Cell Immunol 153(2):443–455. https://doi.org/10.1006/cimm.1994.1041

    Article  CAS  PubMed  Google Scholar 

  28. Kono Y, Fridovich I (1982) Superoxide radical inhibits catalase. J Biol Chem 257(10):5751–5754

    Article  CAS  Google Scholar 

  29. Luck H (1963) Catalase. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 885–888

    Google Scholar 

  30. Moron MS, Depierre JW, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 582(1):67–78. https://doi.org/10.1016/0304-4165(79)90289-7

    Article  CAS  PubMed  Google Scholar 

  31. Zahler WL, Cleland WW (1968) A specific and sensitive assay for disulfides. J Biol Chem 243(4):716–719

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  33. Chadha VD, Bhalla P, Dhawan DK (2008) Zinc modulates lithium-induced hepatotoxicity in rats. Liver Int 28(4):558–565. https://doi.org/10.1111/j.1478-3231.2008.01674.x

    Article  CAS  PubMed  Google Scholar 

  34. Valko M, Morris H, Cronin MTD (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12(10):1161–1208. https://doi.org/10.2174/0929867053764635

    Article  CAS  PubMed  Google Scholar 

  35. Singh MK, Katiyar DK (2019) Medicinal impact of Piper nigrum (piperine ) against arsenic induced hepatic and renal toxicity in experimental mice. Ann Int Med Dental Res 5(4):1

    Article  Google Scholar 

  36. Chasapis CT, Loutsidou AC, Spiliopoulou CA, Stefanidou ME (2012) Zinc and human health: an update. Arch Toxicol 86(4):521–534. https://doi.org/10.1007/s00204-011-0775-1

    Article  CAS  PubMed  Google Scholar 

  37. Bera AK, Rana T, Das S, Bandyopadhyay S, Bhattacharya D, Pan D, Das SK (2010) L-Ascorbate protects rat hepatocytes against sodium arsenite—induced cytotoxicity and oxidative damage. Hum Exp Toxicol 29(2):103–111. https://doi.org/10.1177/0960327109357215

    Article  CAS  PubMed  Google Scholar 

  38. Fouad AA, Al-Mulhim AS, Jresat I (2012) Telmisartan treatment attenuates arsenic-induced hepatotoxicity in mice. Toxicology 300(3):149–157. https://doi.org/10.1016/j.tox.2012.06.015

    Article  CAS  PubMed  Google Scholar 

  39. Adil M, Kandhare A, Visnagri A, Bodhankar S (2015) Naringin ameliorates sodium arsenite-induced renal and hepatic toxicity in rats: decisive role of KIM-1, Caspase-3, TGF-β, and TNF-α. Ren Fail 37(8):1396–1407. https://doi.org/10.3109/0886022X.2015.1074462

    Article  CAS  PubMed  Google Scholar 

  40. Meenakshi SR, Agarwal R (2013) Nitric oxide levels in patients with chronic renal disease. J Clin Diagn Res 7(7):1288. https://doi.org/10.7860/JCDR/2013/5972.3119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Clancy RM, Abramson SB (1995) Nitric oxide: a novel mediator of inflammation. Proc Soc Exp Biol Med 210(2):93–101. https://doi.org/10.3181/00379727-210-43927aa

    Article  CAS  PubMed  Google Scholar 

  42. Cortese-Krott MM, Kulakov L, Opländer C, Kolb-Bachofen V, Kröncke KD, Suschek CV (2014) Zinc regulates iNOS-derived nitric oxide formation in endothelial cells. Redox Biol 2:945–954. https://doi.org/10.1016/j.redox.2014.06.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Nandi D, Chandra-Patra R, Ranjan R, Swarup D (2008) Role of co-administration of antioxidants in prevention of oxidative injury following sub-chronic exposure to arsenic in rats. Veterinarski Arhiv 78(2):113–121

    CAS  Google Scholar 

  44. Hayakawa T, Kobayashi Y, Cui X, Hirano S (2005) A new metabolic pathway of arsenite: arsenic–glutathione complexes are substrates for human arsenic methyltransferase Cyt19. Arch Toxicol 79(4):183–191. https://doi.org/10.1007/s00204-004-0620-x

    Article  CAS  PubMed  Google Scholar 

  45. Manna P, Sinha M, Sil PC (2008) Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid. Arch Toxicol 82(3):137–149. https://doi.org/10.1007/s00204-007-0272-8

    Article  CAS  PubMed  Google Scholar 

  46. Gurer H, Ercal N (2000) Can antioxidants be beneficial in the treatment of lead poisoning? Free Radic Biol Med 29(10):927–945. https://doi.org/10.1016/S0891-5849(00)00413-5

    Article  CAS  PubMed  Google Scholar 

  47. Kharroubi W, Dhibi M, Mekni M, Haouas Z, Chreif I, Neffati F, Hammami M, Sakly R (2014) Sodium arsenate induce changes in fatty acids profiles and oxidative damage in kidney of rats. Environ Sci Pollut Res Int 21(20):12040–12049. https://doi.org/10.1007/s11356-014-3142-y

    Article  CAS  PubMed  Google Scholar 

  48. Kalia K, Narula GD, Kannan GM, Flora SJS (2007) Effects of combined administration of captopril and DMSA on arsenite induced oxidative stress and blood and tissue arsenic concentration in rats. Comp Biochem Physiol C Toxicol Pharmacol 144(4):372–379

    Article  Google Scholar 

  49. Pineda J, Herrera A, Antonio MT (2013) Comparison between hepatic and renal effects in rats treated with arsenic and/or antioxidants during gestation and lactation. J Trace Elem Med Biol 27(3):236–241. https://doi.org/10.1016/j.jtemb.2012.12.006

    Article  CAS  PubMed  Google Scholar 

  50. Oteiza PI (2012) Zinc and the modulation of redox homeostasis. Free Radic Biol Med 53(9):1748–1759. https://doi.org/10.1016/j.freeradbiomed.2012.08.568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Zhang W, Liu Y, Ge M, Jing J, Chen Y, Jiang H, Yu H, Li N, Zhang Z (2014) Protective effect of resveratrol on arsenic trioxide-induced nephrotoxicity in rats. Nutr Res Pract 8(2):220–226. https://doi.org/10.4162/nrp.2014.8.2.220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Sharma B, Singh S, Siddiqi NJ (2014) Biomedical implications of heavy metals induced imbalances in redox systems. Biomed Res Int:640754

  53. Samir D, Zine K (2013) Preventive effect of zinc on nickel-induced oxidative liver injury in rats. African J Biotech 12(51):7112–7119. https://doi.org/10.5897/AJB2013.12962

    Article  CAS  Google Scholar 

  54. Sharma A, Sharma MK, Kumar M (2009) Modulatory role of Emblica officinalis fruit extract against arsenic induced oxidative stress in Swiss albino mice. Chem Biol Interact 180(1):20–30. https://doi.org/10.1016/j.cbi.2009.01.012

    Article  CAS  PubMed  Google Scholar 

  55. Souza ACF, Bastos DSS, Santos FC, Sertorio MN, Ervilha LOG, Gonçalves RV, de-Oliveira LL, Machado-Neves M (2018) Arsenic aggravates oxidative stress causing hepatic alterations and inflammation in diabetic rats. Life Sci 209:472–480. https://doi.org/10.1016/j.lfs.2018.08.054

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Roobee Garla received the financial assistance provided by Indian Council Medical Research (ICMR), India, in the form of Research Associateship (3/1/2/12(Env) SRF 2015-NCD-I). This work is funded by the University Grants Commission Department of Atomic Energy (UGC-DAE) Consortium for Scientific Research, Kolkatta, India (UGC-DAE-CSR-KC/CRS/19/TE03/1073/1089). This work is supported by the Department of Science and Technology (DST) scheme for Promotion of University Research and Scientific Excellence (Purse). Fund for Improvement of S&T Infrastructure in Universities and Higher Educational Institutions (FIST) Program of DST and SAP (Special Assistance Program) scheme from UGC are grealfully acknowledged providing different facilities in the central instrument room of Department of Biophysics, Panjab University, Chandigarh.

Author information

Authors and Affiliations

  1. Department of Biophysics, South Campus, Panjab University, Chandigarh, 160014, India

    Roobee Garla, Nikita Sharma,  Shamli, Naveen Kaushal & Mohan Lal Garg

Authors
  1. Roobee Garla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nikita Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shamli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Naveen Kaushal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohan Lal Garg
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NA

Corresponding author

Correspondence to Roobee Garla.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethics Approval

All the protocols performed were approved (PU/45/99/CPCSEA/IAEC/2018/152) by the Animal Ethical Committee (IAEC) (NIH publications; Rule No. 23-85, as revised in 1985) of Panjab University, Chandigarh, India.

Code Availability

NA

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Garla, R., Sharma, N., Shamli et al. Effect of Zinc on Hepatic and Renal Tissues of Chronically Arsenic Exposed Rats: A Biochemical and Histopathological Study. Biol Trace Elem Res 199, 4237–4250 (2021). https://doi.org/10.1007/s12011-020-02549-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-020-02549-2

Keywords

Search

Navigation