Skip to main content

Advertisement

Log in

Alterations in Blood Metabolic Parameters of Immature Mice After Subchronic Exposure to Cobalt Chloride

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

Abstract

The wide use of cobalt (Co) in food, industry, and medical devices requires full elucidation of its biological effects on tissues and organs. The aim was to assess serum metabolic alterations in immature mice after subchronic exposure to CoCl2. Pregnant ICR mice were subjected to a daily dose of 75 mg cobalt chloride/kg body weight (CoCl2x6H2O) 2–3 days before they gave birth, and treatment continued until days 25 and 30 after delivery. The compound was dissolved in and obtained with regular tap water. ICP-DRC-MS analysis showed significantly elevated serum Co2+ and diverse alterations in metabolic parameters of 25- and 30-day-old pups after exposure to CoCl2. Cholesterol and urea levels were significantly elevated in day 25 mice while HDL-C and LDL-C were reduced. In day 30, Co-exposed mice LDL-C and triglycerides were significantly increased while the total cholesterol level remained unchanged. Alkaline phosphatase was significantly reduced in day 25 Co-exposed mice. Blood glucose level of Co-exposed mice remained close to the untreated controls. Total protein content was slightly increased in day 30 mice. Co-exposure reduced albumin content and albumin/globulin ratio but increased significantly globulin content. Co administration showed strong correlation with cholesterol, urea, and HDL-C in both day 25 and 30 mice. Inverse correlation was found with alkaline phosphatase and albumin for day 25 and with triglycerides, globulin, and total protein content in day 30 Co-exposed mice. Subchronic CoCl2 exposure of immature mice induced significant changes in key metabolic parameters suggesting possible further disturbances in energy metabolism, osteogenesis, and reproduction.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for cobalt 2004

  2. Al-Habsi K, Johnson EH, Kadim IT, Srikandakumar A, Annamalai K, Al-Busaidy R, Mahgoub O (2007) Effects of low concentrations of dietary cobalt on liveweight gains, haematology, serum vitamin B(12) and biochemistry of Omani goats. Vet J 173:131–137

    Article  CAS  Google Scholar 

  3. Bosco G, Paoli A, Rizzato A, Marcolin G, Guagnano MT, Doria C, Bhandari S, Pietrangelo T, Verratti V (2019) Body composition and endocrine adaptations to high-altitude. Adv Exp Med Biol 1211:61–68

    Article  CAS  Google Scholar 

  4. Burns TA, Dembek KA, Kamr A, Dooley SB, Dunbar LK, Aarnes TK, Bednarski LS, O'Brien C, Lakritz J, Byrum B, Wade A, Farmer R, Tan S, Toribio RE (2018) Effect of intravenous administration of cobalt chloride to horses on clinical and hemodynamic variables. J Vet Intern Med 32:441–449

    Article  CAS  Google Scholar 

  5. Busher J (1990) Chapter 101: serum albumin and globulin. In: Walker HK, Hall WD, Hurst JW (eds) Clinical methods: the history, physical, and laboratory examinations, 3rd edn. Butterworths, Boston

    Google Scholar 

  6. Caserta D, Graziano A, Lo Monte G, Bordi G, Moscarini M (2013) Heavy metals and placental fetal-maternal barrier: a mini-review on the major concerns. Eur Rev Med Pharmacol Sci 17(16):2198–2206

    CAS  PubMed  Google Scholar 

  7. Catalani S, Leone R, Rizzetti MC, Padovani A, Apostoli P (2011) The role of albumin in human toxicology of cobalt: contribution from a clinical case. ISRN Hematol 2011:1–6. https://doi.org/10.5402/2011/690620

    Article  CAS  Google Scholar 

  8. Charette RS, Neuwirth AL, Nelson CL (2017) Arthroprosthetic cobaltism associated with cardiomyopathy. Arthroplast Today 3:225–228

    Article  Google Scholar 

  9. Chen Y, Zhao Q, Yang X, Yu X, Yu D, Zhao W (2019) Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth. Cell Stress Chaperones 24:527–538

    Article  CAS  Google Scholar 

  10. Coverdale JPC, Katundu KGH, Sobczak AIS, Arya S, Blindauer CA, Stewart AJ (2018) Ischemia-modified albumin: crosstalk between fatty acid and cobalt binding. Prostaglandins Leukot Essent Fatty Acids 135:147–157

    Article  CAS  Google Scholar 

  11. Danzeisen R, Williams DL, Viegas V, Dourson M, Verberckmoes S, Burzlaff A (2020) Bioelution, bioavailability, and toxicity of cobalt compounds correlate. Toxicol Sci 174:311–325. https://doi.org/10.1093/toxsci/kfz249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dzugkoev SG, Mozhayeva IV, Gigolaeva LB, Tedtoeva AI, Margieva OI, Dzugkoeva FS (2014) The changes in the biochemical indices of blood in cobalt intoxication on the background of the regulators of the expression of endothelial NO-synthase. Patol Fiziol Eksp Ter 58:66–70

    Google Scholar 

  13. Fritzsche J, Borisch C, Schaefer C (2012) Case report: high chromium and cobalt levels in a pregnant patient with bilateral metal-on-metal hip arthroplasties. Clin Orthop Relat Res 470:2325–2331

    Article  Google Scholar 

  14. Garoui el M, Fetoui H, Ayadi Makni F, Boudawara T, Zeghal N (2011) Cobalt chloride induces hepatotoxicity in adult rats and their suckling pups. Exp Toxicol Pathol 63:9–15

    Article  Google Scholar 

  15. Higgins JP, Tuttle TD, Higgins CL (2010) Energy beverages: content and safety. Mayo Clin Proc 85:1033–1041

    Article  CAS  Google Scholar 

  16. Hokin B, Adams M, Ashton J, Louie H (2004) Comparison of the dietary cobalt intake in three different Australian diets. Asia Pac J Clin Nutr 13:289–291

    CAS  PubMed  Google Scholar 

  17. Hsu SH, Chen CT, Wei YH (2013) Inhibitory effects of hypoxia on metabolic switch and osteogenic differentiation of human mesenchymal stem cells. Stem Cells 31:2779–2788

    Article  CAS  Google Scholar 

  18. International Agency for Research on Cancer (IARC) (2006) Metallic cobalt particles (with or without tungsten carbide). In Cobalt in hard metals. IARC monographs on the evaluation of carcinogenic risks to humans, vol. 86, International Agency for Research on Cancer, Lyon, France, pp. 39–155

  19. Kaliman PA, Shalamov RV, Zagaiko AL (1997) Effect of cobalt chloride on content of lipids and lipoproteins in serum and liver of rats. Biochemistry (Mosc) 62:725–731

    CAS  Google Scholar 

  20. Kawakami T, Hanao N, Nishiyama K, Kadota Y, Inoue M, Sato M, Suzuki S (2012) Differential effects of cobalt and mercury on lipid metabolism in the white adipose tissue of high-fat diet-induced obesity mice. Toxicol Appl Pharmacol 258:32–42

    Article  CAS  Google Scholar 

  21. Laksana K, Sooampon S, Pavasant P, Sriarj W (2017) Cobalt chloride enhances the stemness of human dental pulp cells. J Endod 43:760–765

    Article  Google Scholar 

  22. Leyssens L, Vinck B, Van DerStraeten C, Wuyts F, Maes L (2017) Cobalt toxicity in humans. A review of the potential sources and systemic health effects. Toxicology 387:43–56

    Article  CAS  Google Scholar 

  23. Li ZJ, Liang CM, Xia X, Huang K, Yan SQ, Tao RW, Pan WJ, Sheng J, Tao YR, Xiang HY, Hao JH, Wang QN, Tong SL, Tao FB (2019) Association between maternal and umbilical cord serum cobalt concentration during pregnancy and the risk of preterm birth: the Ma’anshan birth cohort (MABC) study. Chemosphere 218:487–492

    Article  CAS  Google Scholar 

  24. Lippi G, Franchini M, Guidi GC (2005) Cobalt chloride administration in athletes: a new perspective in blood doping? Br J Sports Med 39:872–873

    Article  CAS  Google Scholar 

  25. Liu Y, Wang C, Wang Y, Ma Z, Xiao J, McClain C, Li X, Feng W (2012) Cobalt chloride decreases fibroblast growth factor-21 expression dependent on oxidative stress but not hypoxia-inducible factor in Caco-2 cells. Toxicol Appl Pharmacol 264:212–221

    Article  CAS  Google Scholar 

  26. Lu J, Stewart AJ, Sadler PJ, Pinheiro TJ, Blindauer CA (2012) Allosteric inhibition of cobalt binding to albumin by fatty acids: implications for the detection of myocardial ischemia. J Med Chem 55:4425–4430

    Article  CAS  Google Scholar 

  27. Marques AP, Rosmaninho-Salgado J, Estrada M, Cortez V, Nobre RJ, Cavadas C (2017) Hypoxia mimetic induces lipid accumulation through mitochondrial dysfunction and stimulates autophagy in murine preadipocyte cell line. Biochimica et Biophysica Acta (BBA)-General Subjects 1861:673–682

    Article  CAS  Google Scholar 

  28. McCarthy EM, Floyd H, Addison O, Zhang ZJ, Oppenheimer PG, Grover LM (2018) Influence of cobalt ions on collagen gel formation and their interaction with osteoblasts. ACS Omega 3:10129–10138

    Article  CAS  Google Scholar 

  29. Nechev J, Stefanov K, Popov S (2006) Effect of cobalt ions on lipid and sterol metabolism in the marine invertebrates Mytilus galloprovincialis and Actinia equina. Comp Biochem Physiol A Mol Integr Physiol 144:112–118

    Article  Google Scholar 

  30. Nordestgaard BG, Varbo A (2014) Triglycerides and cardiovascular disease. Lancet 384:626–635

    Article  CAS  Google Scholar 

  31. Padilla MA, Elobeid M, Ruden DM, Allison DB (2010) An examination of the association of selected toxic metals with total and central obesity indices: NHANES 99-02. Int J Environ Res Public Health 7:3332–3347

    Article  CAS  Google Scholar 

  32. Rudge CV, Röllin HB, Nogueira CM, Thomassen Y, Rudge MC, Odland JØ (2009) The placenta as a barrier for toxic and essential elements in paired maternal and cord blood samples of South African delivering women. J Environ Monit 11:1322–1330

    Article  CAS  Google Scholar 

  33. Salloum Z, Lehoux EA, Harper ME, Catelas I (2018) Effects of cobalt and chromium ions on oxidative stress and energy metabolism in macrophages in vitro. J Orthop Res 36:3178–3187

    Article  CAS  Google Scholar 

  34. Sankar KS, Altamentova SM, Rocheleau JV (2019) Hypoxia induction in cultured pancreatic islets enhances endothelial cell morphology and survival while maintaining beta-cell function. PLoS One 14(10):e0222424. https://doi.org/10.1371/journal.pone.0222424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Saxena S, Shukla D, Bansal A (2012) Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride. Toxicol Appl Pharmacol 264:324–334

    Article  CAS  Google Scholar 

  36. Simonsen LO, Harbak H, Bennekou P (2012) Cobalt metabolism and toxicology-a brief update. Sci Total Environ 432:210–215

    Article  CAS  Google Scholar 

  37. Skalny AV, Zaitseva IP, Gluhcheva YG, Skalny AA, Achkasov EE, Skalnaya MG, Tinkov AA (2019) Cobalt in athletes: hypoxia and doping - new crossroads. J Appl Biomed 17:28

    Article  Google Scholar 

  38. Vasudevan H, McNeill JH (2007) Chronic cobalt treatment decreases hyperglycemia in streptozotocin-diabetic rats. Biometals 20:129–134

    Article  CAS  Google Scholar 

  39. Warburton A, Girdler SJ, Mikhail CM, Ahn A, Cho SK (2019) Biomaterials in spinal implants: a review. Neurospine. https://doi.org/10.14245/ns.1938296.148

  40. Zheng Y, Yang Y, Deng Y (2019) Dual therapeutic cobalt-incorporated bioceramics accelerate bone tissue regeneration. Mater Sci Eng C Mater Biol Appl 99:770–782

    Article  CAS  Google Scholar 

Download references

Funding

The study was supported by Grants No. DNTS/Russia 02/1/14.06.2018 from the Bulgarian National Science Fund and No. 18-54-18006 from the Russian Foundation for Basic Research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yordanka Gluhcheva.

Ethics declarations

This experimental design was carried out in accordance with guidelines EU Directive 2010/63/EU for animal experiments. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Conflict of Interest

The authors declare that they have no competing interests.

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

Vladov, I., Petrova, E., Pavlova, E. et al. Alterations in Blood Metabolic Parameters of Immature Mice After Subchronic Exposure to Cobalt Chloride. Biol Trace Elem Res 199, 588–593 (2021). https://doi.org/10.1007/s12011-020-02161-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-020-02161-4

Keywords

Navigation