Oxidative Stress Parameters, Trace Elements, and Lipid Profile in Iranian Patients with Gaucher Disease

  • Hadi Mozafari
  • Shohreh Khatami
  • Amir Kiani
  • Zohreh Rahimi
  • Asad Vaisi-Raygani
  • Azam Afsharnaderi
  • Mohammad Reza AlaeiEmail author


Gaucher disease (GD) is most frequent disorder of glycolipid storage. The glucosylceramide accumulation might lead to oxidative stress and changes in lipid profile. Regarding the main role of trace elements in hematopoiesis and oxidative stress, this study was aimed to evaluate the zinc and copper levels, three oxidative stress parameters, and lipid profile in GD. Thirty-three patients with GD along with 64 age- and sex-matched healthy controls participated in the study. The levels of zinc and copper were determined using atomic absorption/flame emission spectrophotometer. Malondialdehyde level was measured using HPLC. Total antioxidant capacity (TAC), catalase activity, and lipid profile were assessed using colorimetric methods. Data were analyzed using SPSS software version 16.0. Significant decrease in the serum levels of Zn (p < 0.001) and Cu (p < 0.001) was observed in patients with GD compared to controls. Subjects in control group showed significantly higher levels of TAC than patients with GD (p < 0.001). In contrast, plasma concentration of malondialdehyde was insignificantly higher in patients with GD than controls (p = 0.06). There was a direct correlation between TAC and hemoglobin concentration (p = 0.035; r = 0.369) in patients with GD. Furthermore, the calculated area under receiver operating characteristic curve for HDL cholesterol was equal to 0.938. The results showed that both zinc and copper levels decreased in patients with GD. Patients with GD showed decreased serum content of TAC. It was found that improving the deficiency of zinc and copper by supplementing them could be useful in management of patients with GD.


Gaucher disease Trace element Oxidative stress Lipid profile 



We gratefully acknowledge the supports by Pasteur Institute of Iran. We also thank the staffs of Tarbiat Modares University, Kermanshah University of Medical Sciences, and Mofid Children’s Hospital of Tehran, Iran.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The study protocol was approved by the Ethics Committee of Pasteur Institute of Iran, and all procedures were in accordance with the ethical standards of the institutional research committee.


  1. 1.
    Beutler E, Grabowski GA (2001) Gaucher disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 3635–3668Google Scholar
  2. 2.
    Pacheco N, Uribe A (2013) Enzymatic analysis of biomarkers for the monitoring of Gaucher patients in Colombia. Gene 521(1):129–135CrossRefGoogle Scholar
  3. 3.
    Jack A, Amato D, Morris G, Choy FY (2014) Two novel mutations in glucocerebrosidase, C23W and IVS7-1 G>A, identified in type 1 Gaucher patients heterozygous for N370S. Gene 538(1):84–87CrossRefGoogle Scholar
  4. 4.
    Schwartz IVD, Göker-Alpan Ö, Kishnani PS et al (2017) Characteristics of 26 patients with type 3 Gaucher disease: a descriptive analysis from the Gaucher Outcome Survey. Mol Genet Metab Rep 14:73–79CrossRefGoogle Scholar
  5. 5.
    Canda E, Kose M, Kagnici M, Ucar SK, Sozmen EY, Coker M (2018) Patients with Gaucher type 1: switching from imiglucerase to miglustat therapy. Blood Cells Mol Dis 68:180–184CrossRefGoogle Scholar
  6. 6.
    Mello AS, da Silva Garcia C, de Souza Machado F, da Silva Medeiros N, Wohlenberg MF, Marinho JP, Dani C, Funchal C, Coelho JC (2015) Oxidative stress parameters of Gaucher disease type I patients. Mol Genet Metab Rep 4:1–5CrossRefGoogle Scholar
  7. 7.
    Zahran AM, Elsayh KI, El-Deek SE, El-Baz MA (2015) Oxidative stress, trace elements, and circulating microparticles in patients with Gaucher disease before and after enzyme replacement therapy. Clin Appl Thromb Hemost 21:58–65CrossRefGoogle Scholar
  8. 8.
    Agarwal R, Chase SD (2002) Rapid, fluorimetric-liquid chromatographic determination of malondialdehyde in biological samples. J Chromatogr B Anal Technol Biomed Life Sci 775:121–126CrossRefGoogle Scholar
  9. 9.
    Roversi FM, Galdieri LC, Grego BH et al (2006) Blood oxidative stress markers in Gaucher disease patients. Clin Chim Acta 364:316–320CrossRefGoogle Scholar
  10. 10.
    Raghavan S, Subramaniyam G, Shanmugam N (2012) Proinflammatory effects of malondialdehyde in lymphocytes. J Leukoc Biol 92:1055–1067CrossRefGoogle Scholar
  11. 11.
    Gong J, Xiao M (2018) Effect of organic selenium supplementation on selenium status, oxidative stress, and antioxidant status in selenium-adequate dairy cows during the periparturient period. Biol Trace Elem Res 186:430–440CrossRefGoogle Scholar
  12. 12.
    Lee YH, Bang ES, Lee JH, Lee JD, Kang DR, Hong J, Lee JM (2018) Serum concentrations of trace elements zinc, copper, selenium, and manganese in critically ill patients. Biol Trace Elem Res 188:316–325. CrossRefGoogle Scholar
  13. 13.
    Manafikhi H, Drummen G, Palmery M, Peluso I (2017) Total antioxidant capacity in beta-thalassemia: a systematic review and meta-analysis of case-control studies. Crit Rev Oncol Hematol 110:35–42CrossRefGoogle Scholar
  14. 14.
    Zekavat OR, Bahmanjahromi A, Haghpanah S, Ebrahimi S, Cohan N (2018) The zinc and copper levels in thalassemia major patients, receiving iron chelation therapy. J Pediatr Hematol Oncol 40:178–181CrossRefGoogle Scholar
  15. 15.
    Michalska-Mosiej M, Socha K, Soroczyńska J et al (2016) Selenium, zinc, copper, and total antioxidant status in the serum of patients with chronic tonsillitis. Biol Trace Elem Res 173:30–34CrossRefGoogle Scholar
  16. 16.
    Watad S, Abu-Saleh N, Yousif A, Agbaria A, Rosenbaum H (2018) The role of high density lipoprotein in type 1 Gaucher disease. Blood Cells Mol Dis 68:43–46CrossRefGoogle Scholar
  17. 17.
    Cenarro A, Pocovi M, Giraldo P, Garcia-Otin AL, Ordovas JM (1999) Plasma lipoprotein responses to enzyme-replacement in Gaucher’s disease. Lancet 353:642–643CrossRefGoogle Scholar
  18. 18.
    Mozafari H, Taghikhani M, Khatami S, Alaei MR, Vaisi-Raygani A, Rahimi Z (2016) Chitotriosidase activity and gene polymorphism in Iranian patients with Gaucher disease and sibling carriers. Iran J Child Neurol 10:62–70Google Scholar
  19. 19.
    Sista RS, Wang T, Wu N, Graham C, Eckhardt A, Bali D, Millington DS, Pamula VK (2013) Rapid assays for Gaucher and Hurler diseases in dried blood spots using digital microfluidics. Mol Genet Metab 109:218–220CrossRefGoogle Scholar
  20. 20.
    Hollak CE, van Weely S, van Oers MH, Aerts JM (1994) Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. J Clin Invest 93:1288–1292CrossRefGoogle Scholar
  21. 21.
    Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76CrossRefGoogle Scholar
  22. 22.
    Khoschsorur GA, Winklhofer-Roob BM, Rabl H, Auer T, Peng Z, Schaur RJ (2000) Evaluation of a sensitive HPLC method for the determination of malondialdehyde, and application of the method to different biological materials. Chromatographia 52:181–184CrossRefGoogle Scholar
  23. 23.
    Goth L (1991) A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta 196:143–151CrossRefGoogle Scholar
  24. 24.
    Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499e502Google Scholar
  25. 25.
    Oteiza PI, Mackenzie GG, Verstraeten SV (2004) Metals in neurodegeneration: involvement of oxidants and oxidant-sensitive transcription factors. Mol Asp Med 25:103–115CrossRefGoogle Scholar
  26. 26.
    Zago MP, Oteiza PI (2001) The antioxidant properties of zinc: interactions with iron and antioxidants. Free Radic Biol Med 31:266–274CrossRefGoogle Scholar
  27. 27.
    Fairweather-Tait SJ, Cashman K (2015) Minerals and trace elements. World Rev Nutr Diet 111:45–52CrossRefGoogle Scholar
  28. 28.
    Gaffney-Stomberg E (2018) The impact of trace minerals on bone metabolism. Biol Trace Elem Res 188:26–34. CrossRefGoogle Scholar
  29. 29.
    John L (2012) Update on anemia and neutropenia in copper deficiency. Curr Opin Hematol 19:58–60CrossRefGoogle Scholar
  30. 30.
    Ghiselli A, Serafini M, Natella F, Scaccini C (2000) Total antioxidant capacity as a tool to assess redox status: critical view and experimental data. Free Radic Biol Med 29:1106–1114CrossRefGoogle Scholar
  31. 31.
    Deganuto M, Pittis MG, Pines A, Dominissini S, Kelley MR, Garcia R, Quadrifoglio F, Bembi B, Tell G (2007) Altered intracellular redox status in Gaucher disease fibroblasts and impairment of adaptive response against oxidative stress. J Cell Physiol 212:223–235CrossRefGoogle Scholar
  32. 32.
    Jmoudiak M, Futerman AH (2005) Gaucher disease: pathological mechanisms and modern management. Br J Haematol 129:178–188CrossRefGoogle Scholar
  33. 33.
    Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23–35CrossRefGoogle Scholar
  34. 34.
    Moraitou M, Dimitriou E, Dekker N, Monopolis I, Aerts J, Michelakakis H (2014) Gaucher disease: plasmalogen levels in relation to primary lipid abnormalities and oxidative stress. Blood Cells Mol Dis 53:30–33CrossRefGoogle Scholar
  35. 35.
    Maccio A, Madeddu C, Massa D et al (2005) Hemoglobin levels correlate with interleukin-6 levels in patients with advanced untreated epithelial ovarian cancer: role of inflammation in cancer-related anemia. Blood 106:362–367CrossRefGoogle Scholar
  36. 36.
    Akca H, Polat A, Koca C (2013) Determination of total oxidative stress and total antioxidant capacity before and after the treatment of iron-deficiency anemia. J Clin Lab Anal 27:227–230CrossRefGoogle Scholar
  37. 37.
    Bitla ARKN, Reddy NS, Nagaraju KV et al (2012) Antioxidant status in patients with metabolic syndrome as measured by ferric reducing ability of plasma (FRAP) assay. J Clin Sci Res 3:114–120Google Scholar
  38. 38.
    Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114:1752–1761CrossRefGoogle Scholar
  39. 39.
    Puzo J, Alfonso P, Irun P, Gervas J, Pocovi M, Giraldo P (2010) Changes in the atherogenic profile of patients with type 1 Gaucher disease after miglustat therapy. Atherosclerosis 209:515–519CrossRefGoogle Scholar
  40. 40.
    Tabet F, Rye KA (2009) High-density lipoproteins, inflammation and oxidative stress. Clin Sci (Lond) 116:87–98.
  41. 41.
    Benzie IF, Devaki M (2018) The ferric reducing/antioxidant power (FRAP) assay for non‐enzymatic antioxidant capacity: concepts, procedures, limitations and applications. In: Apak R, Capanoglu E, Shahidi F (eds) Measurement of antioxidant activity & capacity: recent trends and applications. Wiley, New York pp 77–106Google Scholar
  42. 42.
    Lemos BS, Medina-Vera I, Blesso CN, Fernandez ML (2018) Intake of 3 eggs per day when compared to a choline bitartrate supplement, downregulates cholesterol synthesis without changing the LDL/HDL ratio. Nutrients 10(2)Google Scholar
  43. 43.
    Lemieux I, Lamarche B, Couillard C, Pascot A, Cantin B, Bergeron J, Dagenais GR, Després JP (2001) Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study. Arch Intern Med 161:2685–2692CrossRefGoogle Scholar
  44. 44.
    Zimmermann A, Grigorescu-Sido P, Rossmann H, Lackner KJ, Drugan C, al Khzouz C, Bucerzan S, Naşcu I, Zimmermann T, Leucuţa D, Weber MM (2013) Dynamic changes of lipid profile in Romanian patients with Gaucher disease type 1 under enzyme replacement therapy: a prospective study. J Inherit Metab Dis 36:555–563CrossRefGoogle Scholar
  45. 45.
    de Fost M, Langeveld M, Franssen R, Hutten BA, Groener JEM, de Groot E, Mannens MM, Bikker H, Aerts JMFG, Kastelein JJP, Hollak CEM (2009) Low HDL cholesterol levels in type I Gaucher disease do not lead to an increased risk of cardiovascular disease. Atherosclerosis 204:267–272CrossRefGoogle Scholar
  46. 46.
    Pocovi M, Cenarro A, Civeira F, Torralba MA, Perez-Calvo JI, Mozas P, Giraldo P, Giralt M, Myers RH, Cupples LA, Ordovas JM (1998) Beta-glucocerebrosidase gene locus as a link for Gaucher’s disease and familial hypo-alpha-lipoproteinaemia. Lancet 351:1919–1923CrossRefGoogle Scholar
  47. 47.
    Gammon CS, Kruger R, Minihane AM et al (2013) Kiwifruit consumption favorably affects plasma lipids in a randomised controlled trial in hypercholesterolaemic men. Br J Nutr 109:2208–2218CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Medical biology Research CenterKermanshah University of Medical SciencesKermanshahIran
  2. 2.Department of Clinical Biochemistry, Medical SchoolKermanshah University of Medical SciencesKermanshahIran
  3. 3.Department of BiochemistryPasteur Institute of IranTehranIran
  4. 4.Regenerative Medicine Research Center (RMRC)Kermanshah University of Medical SciencesKermanshahIran
  5. 5.Fertility and Infertility Research CenterKermanshah University of Medical SciencesKermanshahIran
  6. 6.Department of Clinical Biochemistry, Faculty of Medical SciencesTarbiat Modares UniversityTehranIran
  7. 7.Department of Pediatric Endocrinology, Faculty of MedicineShahid Beheshti University Of Medical SciencesTehranIran

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