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Modulation of Superoxide Dismutase Activity by Mercury, Lead, and Arsenic

  • Abhishek Kumar
  • Khushboo
  • Rukmani Pandey
  • Bechan SharmaEmail author
Article
  • 16 Downloads

Abstract

Arsenic, mercury and lead are the environmental toxicants which exert their toxic effects through binding with certain proteins including their structures and functions. The toxicity of these heavy metal results is associated to its interaction with the metalloenzymes. They replace the essential metals required for normal biochemical functions of enzymes. The superoxide dismutase (SOD), a metalloenzyme, requires certain cofactors such as Cu2+ and Zn2+ for their optimal activity. However, the studies on the in vitro kinetic characterization of SOD from the rat liver cytosolic fraction have not been reported. The main objective of this study concerns the determination of the effect of three heavy metals such as arsenic, mercury, and lead on the activity of cytosolic SOD isolated from post nuclear supernatant (PNS) of rat liver. The activity of SOD was calculated using pyrogallol as a substrate. The stability and the sensitivity of enzyme activity were measured by assaying the enzyme activity at different temperature conditions. In order to determine the IC50 of the heavy metals, the enzyme activity was monitored in the presence of different concentrations of heavy metals. The values of all kinetic parameters including Km, Vmax, and Kcat were calculated by assaying SOD in the presence and absence of heavy metals. The results indicated that these heavy metals were able to significantly modulate the kinetic behavior of hepatic SOD. The data from present study could be utilized to develop suitable antidotes to mitigate the adverse effects of these heavy metals.

Graphical Abstract

Keywords

Lead Arsenic Mercury Superoxide dismutase Hepatotoxicity 

Notes

Acknowledgments

AK and Khushboo are grateful to University Grants Commission-New Delhi for providing financial support in the form of research fellowships. RP acknowledges UGC-New Delhi for providing financial support. The authors acknowledge DST-FIST, New Delhi, and UGC-SAP, New Delhi for providing grants to generate research facilities at the Department of Biochemistry of University of Allahabad, India.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Fattman C L, Schaefer L M, Oury T D (2003) Extracellular superoxide dismutase in biology and medicine. Free Radic Biol MedGoogle Scholar
  2. 2.
    Weisiger RA, Fridovich I (1973) Superoxide dismutase. Organelle specificity. J Biol Chem 248:3582–3592PubMedGoogle Scholar
  3. 3.
    Lassegue B, Griendling KK (2010) NADPH oxidases: functions and pathologies in the vasculature. Arterioscler Thromb Vasc Biol 30:653–661CrossRefGoogle Scholar
  4. 4.
    Go YM, Jones DP (2011) Cysteine/cystine redox signaling in cardiovascular disease. Free Radic Biol MedGoogle Scholar
  5. 5.
    Guzik TJ, Harrison DG (2006) Vascular NADPH oxidases as drug targets for novel antioxidant strategies. Drug Discov Today 11:524–533CrossRefGoogle Scholar
  6. 6.
    Madamanchi NR, Runge MS (2007) Mitochondrial dysfunction in atherosclerosis. Circ Res 100:460–473CrossRefGoogle Scholar
  7. 7.
    Elroy-Stein O, Bernstein Y, Groner Y (1986) Overproduction of human Cu/Zn-superoxide dismutase in transfected cells: extenuation of paraquat-mediated cytotoxicity and enhancement of lipid peroxidation. EMBO J 5:615–622CrossRefGoogle Scholar
  8. 8.
    Fukai T, Ushio-Fukai M (2011) Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox SignalGoogle Scholar
  9. 9.
    Gwaltney-Brant S M (2013) Heavy metals. In Haschek and Rousseaux’s Handbook of Toxicologic PathologyCrossRefGoogle Scholar
  10. 10.
    Tangahu B V, Sheikh Abdullah S R, Basri H, Idris M, Anuar N, Mukhlisin M (2011) A review on heavy metals (As, Pb, and Hg) uptake by plants through phytoremediation. Int J Chem EngGoogle Scholar
  11. 11.
    Kumar A, Sharma B (2018) Consequences of heavy metals pollution in environment and bioremediation practices. In: Bharagava RN (ed) Recent Advances in Environmental Management. CRC Press, Taylor & Francis Group, USA, pp 247–273Google Scholar
  12. 12.
    Hussain S, Atkinson A, Thompson S J, Khan A T (1999) Accumulation of mercury and its effect on antioxidant enzymes in brain, liver, and kidneys of mice. J Environ Sci Heal B Pesticides, Food Contaminants, and Agricultural WastesGoogle Scholar
  13. 13.
    Sharma B, Singh S, Siddiqi NJ (2014) Biomedical implications of heavy metals induced imbalances in redox systems. Biomed Res Int 2014: Article ID 640754Google Scholar
  14. 14.
    Singh N, Kumar A, Gupta V K, Sharma B (2018) Biochemical and molecular bases of lead-induced toxicity in mammalian systems and possible mitigations. Chem Res Toxicol, acs.chemrestox.8b00193Google Scholar
  15. 15.
    Kumar A, Singh N, Pandey R, Gupta V K, Sharma B (2018) Biochemical and molecular targets of heavy metals and their actions. In M. Rai, A. P. Ingle, & S. Medici, eds. Biomedical Applications of Metals. Springer International Publishing AG, part of Springer Nature 2018, pp. 297–319Google Scholar
  16. 16.
    Gupta VK, Kumar A, Yadav SH, Pandey R, Sharma B (2017) Acetylcholinesterase as a biomarker of arsenic induced cardiotoxicity in mammals. Forensic Sci Int 5(4):142–149Google Scholar
  17. 17.
    Rebelo F M, Caldas E D (2016) Arsenic, lead, mercury and cadmium: toxicity, levels in breast milk and the risks for breastfed infants. Environ ResGoogle Scholar
  18. 18.
    Gupta VK, Kumar A, Siddiqi NJ, Sharma B (2016) Rat brain acetyl cholinesterase as a biomarker of cadmium induced neurotoxicity. OAJT 1(1):1–7Google Scholar
  19. 19.
    Duruibe JO, Ogwuegbu MOC, Egwurugwu JN (2007) Heavy metal pollution and human biotoxic effects. Int J Phys Sci.  https://doi.org/10.1155/2014/640754 Google Scholar
  20. 20.
    Mabrouk A, Bel Hadj Salah I, Chaieb W, Ben Cheikh H (2016) Protective effect of thymoquinone against lead-induced hepatic toxicity in rats. Environ Sci Pollut Res 23(12):12206–12215CrossRefGoogle Scholar
  21. 21.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol ChemGoogle Scholar
  22. 22.
    Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47(3):469–474.  https://doi.org/10.1111/j.1432-1033.1974.tb03714 CrossRefPubMedGoogle Scholar
  23. 23.
    Li X, Qiu S, Shi J, Wang S, Wang M, Xu Y, Nie Z, Liu C, Liu C (2019) A new function of copper zinc superoxide dismutase: as a regulatory DNA-binding protein in gene expression in response to intracellular hydrogen peroxide. Nucleic Acids Res 47(10).  https://doi.org/10.1093/nar/gkz256 CrossRefGoogle Scholar
  24. 24.
    Singh N, Gupta VK, Kumar A, Sharma B (2017) Synergistic effects of heavy metals and pesticides in living systems. Front Chem.  https://doi.org/10.3389/fchem.2017.00070
  25. 25.
    Abreu IA, Cabelli DE (2010) Superoxide dismutases-a review of the metal-associated mechanistic variations. Biochim Biophys Acta 1804:263–274CrossRefGoogle Scholar
  26. 26.
    Perelman A, Dubinsky Z, Martínez R (2006) Temperature dependence of superoxide dismutase activity in plankton. J Exp Mar Biol EcolGoogle Scholar
  27. 27.
    Liu P, Guo W Shan, Pu H Chun, Feng C Nian, Zhu X Kai, Peng Y Xin, Zhang Y min (2006) Effects of high temperature on antioxidant enzymes and lipid peroxidation in flag leaves of wheat during grain filling period. Agric Sci ChinaGoogle Scholar
  28. 28.
    Roy S, Roy M, Gupta N, Tandon N (2012) Protective effect of Psidium guajava in arsenic-induced oxidative stress and cytological damage in rats. Toxicol IntGoogle Scholar
  29. 29.
    Kumar A, Dogra S, Prakash A (2009) Protective effect of curcumin (Curcuma longa), against aluminium toxicity: possible behavioral and biochemical alterations in rats. Behav Brain ResGoogle Scholar
  30. 30.
    Jalaludeen A M, Ha W T, Lee R, Kim J H, Do J T, Park C, Heo Y T, Lee W Y, Song H (2016) Biochanin a ameliorates arsenic-induced hepato and hematotoxicity in rats. MoleculesGoogle Scholar
  31. 31.
    Adegbesan B O, Adenuga G A (2007) Effect of lead exposure on liver lipid peroxidative and antioxidant defense systems of protein-undernourished rats. Biol Trace Elem ResGoogle Scholar
  32. 32.
    Keles H, Ince S, Kçkkurt I, Tatli I I, Akkol E K, Kahraman C, Demirel H H (2012) The effects of Feijoa sellowiana fruits on the antioxidant defense system, lipid peroxidation, and tissue morphology in rats. Pharm BiolGoogle Scholar
  33. 33.
    Bekheet S H M, Awadalla E A, Salman M M, Hassan M K (2011) Bradykinin potentiating factor isolated from Buthus occitanus venom has a protective effect against cadmium-induced rat liver and kidney damage. Tissue CellGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of BiochemistryUniversity of AllahabadAllahabadIndia
  2. 2.Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment GroupCSIR-Indian Institute of Toxicology Research (CSIR-IITR)LucknowIndia

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