Export file:


  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text


  • Citation Only
  • Citation and Abstract

Effects of chelating agents on heavy metals in Hepatitis C Virus (HCV) patients

1 Department of Biochemistry, Government College University Faisalabad (GCUF), Pakistan
2 Department of Bioinformatics & Computational biology, Virtual University of Pakistan, Pakistan
3 Department of Zoology, Government College University Faisalabad (GCUF), Pakistan
4 Department of Statistics, Government College University, Faisalabad, Pakistan
5 Health Care Center Government College University Faisalabad (GCUF), Pakistan

Special Issues: State-of-the-art strategies to tackle emerging contaminants of high concern: In greening the 21st - century environmental engineering

Heavy metals are released into the environment through both human and natural sources, may have a direct hepatic toxicity and are involved in chronic liver diseases. Modification in the regulation of heavy metals metabolism enhanced hepatitis c virus (HCV) replication which ultimately reduced outcomes of anti-viral therapy in chronic HCV patients. Chelation therapy with new drugs seems to eradicate HCV and may prevent liver complications. The present study was planned to explore the effects of MiADMSA (lipophilic chelating agent) for achieving maximum heavy metals elimination in hepatitis c virus patients with minimum side effects. For this purpose concentration of heavy metal was determined in HCV patients and established correlation of heavy metals between healthy persons and HCV patients. Atomic absorption spectrophotometer (AAS) was used to explore them. Concentrations of heavy metal in different samples (blood serum, nails and hair) of patients and healthy individuals. Result revealed that heavy metals (Lead, Cobalt, Cadmium, Manganese, Iron and Cooper) concentration were significantly higher in blood of HCV patients as compared to normal persons, but some metals like Ni and Zn were present in normal concentration and in low concentration respectively. After chelation with monoisoamyl DMSA (MiADMSA) a significant amount of heavy metals was excreted in the urine in a dose dependent manner. It was generally observed from the results that TDS is a better treatment option than BD for chelation of heavy metals in hepatitis c virus patients. This chelation therapy will be helpful to reverse the HCV related health problems.
  Article Metrics

Keywords monoisoamyl DMSA; hepatitis c virus; atomic absorption spectrophotometer; chelation; hepatocellular carcinoma

Citation: Nosheen Aslam, Muhammad Sarfaraz Iqbal, Syed Makhdoom Hussain, Muhammad Rizwan, Qurat-Ul-Ain Naseer, Muhammad Afzal, Rizwan Muneer, Farzana Batool. Effects of chelating agents on heavy metals in Hepatitis C Virus (HCV) patients. Mathematical Biosciences and Engineering, 2019, 16(3): 1138-1149. doi: 10.3934/mbe.2019054


  • 1. M. S. Iqbal, U. A. Ashfaq and S. Khaliq, et al., Toll-like receptor 4 polymorphism as pretreatment predictor of response to HCV genotype 3a interferon-based treatment, Future. Med., 12 (2017).
  • 2. A. Arshad and U. A. Ashfaq, Epidemiology of hepatitis c infection in pakistan: Current estimate and major risk factors, 27 (2017), 63–77.
  • 3. M. S. Iqbal, U. A. Ashfaq and S. Aslam, et al., Analysis of polymorphism rs1990760 of IFIH1 gene and treatment outcomes in HCV infection, Future. Virol., 13 (2018).
  • 4. N. Jiwani, N. J. Mscn and R. Gul, A silent storm : Hepatitis C in Pakistan, 1 (2011), 89–91.
  • 5. M. U. Ghani, A. Haque and M. Qasim, et al., Involvement of vascular endothelial growth factor (VEGF) gene polymorphism in hepatocellular carcinoma of HCV patients from local population, Pure. Appl. Biol., 6 (2017), 725–732.
  • 6. R. Aslam, S. M. Raza and H. Naeemi, et al., SOCS3 mRNA expression and polymorphisms as pretreatment predictor of response to HCV genotype 3a IFN-based treatment, SpringerPlus, 5 (2016), 1826.
  • 7. K. Tarao, S. Ohkawa and Y. Miyagi, et al., Inflammation in background cirrhosis evokes malignant progression in HCC development from HCV-associated liver cirrhosis, Scand. J Gastroentero., 48 (2013), 729–735.
  • 8. N. Aslam, F. Batool and M. S. Iqbal, et al., Analysis of Toll-like receptors-9 (TLR9) gene polymorphism (rs5743836) in Pakistani patients with HCV, Pak. J. Pharm. Sci., 31 (2018), 2709–2714.
  • 9. L. Piekuse, M. Kreile and A. Zarina, et al., Association between inherited monogenic liver disorders and chronic hepatitis C, World. J. Hepatol., 6 (2014), 92–97.
  • 10. T. G. Kazi and N. F. Kolachi, Effects of mineral supplementation on liver cirrhotic/cancer male patients, Biol. Trace. Elem. Res., 150 (2012), 81–90.
  • 11. M. Afify, M. Diaa and E. A. Elmaksoud, et al., Serum levels of trace elements in Egyptian patients with chronic hepatitis C under interferon therapy. J. Genet. Eng. Biotechnol., 10 (2012), 81–86.
  • 12. J. E. Gall, R. S. Boyd and N. Rajakaruna, Transfer of heavy metals through terrestrial food webs : A review, Environ. Monit. Assess., 187 (2015), 201.
  • 13. V. M. Varnai, M. Piasek and K. Kostial, Chelators as antidotes of metal toxicity : Therapeutic and experimental aspects, Curr. Med. Chem., 12 (2005), 2771–2794.
  • 14. H. V. Aposhian, R. M. Maiorino and R. C. Dart, et al., Urinary excretion of 1989, 520–526.
  • 15. M. P. Simula and V. De Re, Hepatitis c virus-induced oxidative stress and mitochondrial dysfunction: A focus on recent advances in proteomics, Clin. Appl., 4 (2010), 782–793.
  • 16. M. Vidali, M. F. Tripodi and A. Ivaldi, et al., Interplay between oxidative stress and hepatic steatosis in the progression of chronic hepatitis C, J. Hepatol., 48 (2008), 399–406.
  • 17. S. J. Polyak, C. Morishima and M. C. Shuhart, et al., Inhibition of T-Cell Inflammatory Cytokines, Hepatocyte NF-κB Signaling, and HCV Infection by Standardized Silymarin, Gastroenterology, 132 (2007), 1925–1936.
  • 18. K. H. Ibs and L. Rink, Zinc-Altered Immune function, J. Nutr., 133 (2003), 1452S–1456S.
  • 19. T. Liu, W. He and C. Yan, et al., Roles of reactive oxygen species and mitochondria in cadmium-induced injury of liver cells, Toxicol. Ind. Health, 27 (2010), 249–256.
  • 20. S. Turgut, A. Polat and M. Inan, et al., Interaction between anemia and blood levels of iron, zinc, copper, cadmium and lead in children, Ind. J. Pediatr., 74 (2007), 827–830.
  • 21. B. Halliwell and J. M. C. Gutteridge, Role of free radicals and catalytic metal ions in human disease: An overview, Method. Enzymol., 186 (1990), 1–85.
  • 22. C. Pramoolsinsap, N. Promvanit and S. Komindr, et al., Gastroenterology serum trace metals in chronic viral hepatitis and hepatocellular carcinoma in Thailand, J. Gastroenterol., 29 (1994), 610–615.
  • 23. A. Ipek, E. Barut and H. Gulen, et al., Assessment of inter- and intra-cultivar variations in olive using SSR markers, Sci. Agri., 69 (2012), 327–335.
  • 24. B. M. Science and K. Medical, Selenium, iron, copper, and zinc levels and copper-to-zinc ratios in serum of patients at different stages of viral hepatic diseases, Biol. Trace. Elem. Res., 109 (2006), 15–23.
  • 25. B. Lo, Phytic acid-trace element (Zn, Cu, Mn) interactions, Int. J. Food Sci. Technol., 37 (2002), 749–758.
  • 26. C. M. Lange, Z. Kutalik and K. Morikawa, et al., Serum ferritin levels are associated with a distinct phenotype of chronic hepatitis C poorly responding to pegylated interferon-alpha and ribavirin therapy, Hepatology, 55 (2012), 1038–1047.
  • 27. N. Ganne-Carrié, C. Christidis and C. Chastang, et al., Liver iron is predictive of death in alcoholic cirrhosis: A multivariate study of 229 consecutive patients with alcoholic and/or hepatitis c virus cirrhosis: A prospective follow up study, Gut, 46 (2000), 277–282.
  • 28. H. Ataee-Esfahani, L. Wang and Y. Nemoto, et al., Synthesis of bimetallic Au@Pt nanoparticles with Au core and nanostructured Pt shell toward highly active electrocatalysts, Chem. Mater., 22 (2010), 6310–6318.
  • 29. D. Ozcelik, R. Ozaras and Z. Gurel, et al., Copper-mediated oxidative stress in rat liver, Biol. Trace. Elem. Res., 96 (2003), 209–215.
  • 30. O. Tschritter, A. Fritsche and C. Thamer, et al., Plasma adiponectin concentrations predict insulin sensitivity of both glucose and lipid metabolism, Diabetes, 52 (2003), 239–243.
  • 31. H. Kinoshita, Y. Hori and T. Fukumoto, et al., Novel assessment of hepatic iron distribution by synchrotron radiation X-ray fluorescence microscopy, Med. Mol. Morphol., 43 (2010), 19–25.
  • 32. V. Pachauri and S. Flora, Combined efficacy of gallic acid and MiADMSA with limited beneficial effects over MiADMSA against arsenic-induced oxidative stress in mouse, Biochem. Insights, 8 (2015), 1–10.
  • 33. C. Loguercio, V. De Girolamo and A. Federico, et al., Relationship of blood trace elements to liver damage, nutritional status, and oxidative stress in chronic nonalcoholic liver disease, Biol. Trace. Elem. Res., 81 (2001), 245–254.
  • 34. C. Guo, P. Chen and K. Lin, et al., Trace metal imbalance associated with oxidative stress and inflammatory status in anti-hepatitis c virus antibody, Environ. Toxicol. Phar., 33 (2011), 288–296.
  • 35. A. U. Neumann, N. P. Lam and H. Dahari, et al., Hepatitis c viral dynamics in vivo and the antiviral efficacy of interferon-α therapy, Science, 282 (1998), 103–107.
  • 36. R. Y. Dodd and S. L. Stramer, Transfusion complications, 42 (2002), 975–979.
  • 37. R. Thimme, D, Oldach and K. M. Chang, et al., Determinants of viral clearance and Persistence during Acute hepatitis c virus Infection, J. Exp. Med., 194 (2001), 1395–1406.
  • 38. O. Lesens, M. Desche and M. Steben, Hepatitis c virus is related to progressive liver disease in human immunodeficiency virus-positive hemophiliacs and should be treated as an opportunistic infection, J. Infect. Dis., 179 (1999), 1254–1258.
  • 39. G. D. Kelen, G. B. Green and R. H. Purcell, et al., Hepatitis B and Hepatitis C in emergency department patients, New Engl. J. Med., 326 (1992), 1399–1404.
  • 40. M. El Sayed Zaki and W. Othman, Role of hepatitis E infection in acute on chronic liver failure in Egyptian patients, Liver Int., 31 (2011), 1001–1005.
  • 41. K. Grüngreiff, T. Hebell and K. Gutensohn, et al., Plasma concentrations of zinc, copper, interleukin-6 and interferon-γ, and plasma dipeptidyl peptidase IV activity in chronic hepatitis C, Mol. Med. Rep., 2 (2009), 63–68.
  • 42. K. C. Sorensen, S. Venn-Watson and S. H. Ridgway, Trace and non-trace elements in blood cells of bottlenose dolphins (Tursiops truncatus): Variations with values from liver function indicators, J. Wildlife Dis., 44 (2008), 304–317.
  • 43. M. Takahashi, H. Saito and M. Higashimoto, et al., Possible inhibitory effect of oral zinc supplementation on hepatic fibrosis through downregulation of TIMP-1: A pilot study, Hepatol. Res., 37 (2007), 405–409.
  • 44. T. Himoto, N. Hosomi and S. Nakai, et al., Efficacy of zinc administration in patients with hepatitis c virus-related chronic liver disease, Scand. J. Gastroentero., 42 (2007), 1078–1087.
  • 45. M. Blanuša, L. Prester and M. Piasek, et al., Monoisoamyl ester of DMSA reduces 203Hg(NO3)2 retention in rats: 1. Chelation therapy during pregnancy, J. Trace. Elem. Exp. Med., 10 (1997), 173–181.
  • 46. A. Mehta, S. C. Pant and S. J. S. Flora, Monoisoamyl dimercaptosuccinic acid-induced changes in pregnant female rats during late gestation and lactation, Reprod. Toxicol., 21 (2006), 94–103.


Reader Comments

your name: *   your email: *  

© 2019 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Export Citation

Copyright © AIMS Press All Rights Reserved