Bìol. Tvarin, 2018, volume 20, issue 4, pp. 9–15


O. M. Voloshchuk, G. P. Kopylchuk

This email address is being protected from spambots. You need JavaScript enabled to view it.

Institute of Biology, Chemistry and Bioresources
of Chernivtsi national university named by Yurii Fedkovych,
Biochemistry and biotechnology department,
2 Kotsyubinskogo str., Chernivtsi 58000 Ukraine

The indices of copper metabolism in rats with toxic liver injury on the background of alimentary protein deficiency were studied in the research.

The animals were separated into the following 4 groups: I intact animals (C); II — animals receiving low-protein ration (LPR); III animals subjected to acetaminophen-induced liver lesions receiving complete ration (H); IV animals subjected to acetaminophen-induced liver lesions that were previously fed semi-synthetic low-protein ration (LPR+H). The level of ceruloplasmin in blood plasma was determined by Ravin method based on a photocolorimetrical evaluation of the products of n-phenylamide oxidation by ceruloplasmin. Determination of copper level in blood plasma and urea was conducted using set of reagents (“BIO-LA-TEST”, Czech Republic). Albumin level in blood plasma was evaluated using set of reagents (“Filisit-Diagnostics”, Ukraine).

It is established that in rats with protein deficiency there is a decrease in copper level by 1.6 times comparing to control, along with a significant reduction of ceruloplasmin plasma level as well as an increased loss of copper with urine. The similar changes are found in animals with a modeled toxic liver injury, maintained on a full-value diet.

It is established that the most significant disturbances of copper metabolism are observed in rats with protein deficiency and acetaminophen-induced liver injury. In rats of III group there is a 3-fold decrease in copper level in blood plasma on the background of hypoalbuminemia, and a 2-fold reduction of ceruloplasmin level in blood plasma accompanied by an increased copper content in urine. A depletion of pool of the biologically available copper may further lead to changes in functioning of the copper-dependent enzymes. Thus, it may be considered as a possible mechanism of disturbances of the metabolic processes in conditions of drug-induced intoxications against the background of alimentary protein deficiency.

Obtained changes in copper metabolism indices under the conditions of toxic liver injury on a background of alimentary deprivation of protein open the new prospects for the further research into the activity of copper-containing enzymes and their role in the formation of the metabolic disturbances in the given conditions.


  1. Aigner E., Strasser M., Haufe H., Sonnweber T., Hohla F., Stadlmayr A., Solioz M., Tilg H., Patsch W., Weiss G., Stickel F., Datz C. A Role for Low Hepatic Copper Concentrations in Nonalcoholic Fatty Liver Disease. The American Journal of Gastroenterology, 2010, vol. 105, pp. 1978–1985. https://doi.org/10.1038/ajg.2010.170
  2. Aigner E., Theur I., Haufe H., Seifert M., Hohla F., Scharinger L., Stickel F., Mourlane F., Weiss G., Datz C. Copper availability contributes to iron perturbations in human nonalcoholic fatty liver disease. Gastroenterology, 2008, vol. 135, issue 2, pp. 680–688. https://doi.org/10.1053/j.gastro.2008.04.007
  3. Aliasgharpour M. A review on copper, ceruloplasmin and wilson’s disease. International journal of Medical Investigation, 2015, vol. 4, no. 4, pp. 344–347.
  4. Dongiovanni P., Valent L. A Nutrigenomic Approach to Non-Alcoholic Fatty Liver Disease. International Journal of Molecular Sciences, 2017, vol. 18, issue 7, p. 1534. https://doi.org/10.3390/ijms18071534
  5. Fieten H., Leegwater P. A., Watson A. L., Rothuizen J. Canine models of copper toxicosis for understanding mammalian copper metabolism. Mammalian Genome, 2012, vol. 23, issue 1–2, pp. 62–75. https://doi.org/10.1007/s00335-011-9378-7
  6. Hatano R., Ebara M., Fukuda H., Yoshikawa M., Sugiura N., Kondo F., Yukawa M., Saisho H. Accumulation of copper in the liver and hepatic injury in chronic hepatitis C. J. Gastroenterology and Hepatology, 2000, vol. 15, issue 7, pp. 786–791. https://doi.org/10.1046/j.1440-1746.2000.02199.x
  7. Itoh S., Kim H. W., Nakagawa O., Ozumi K., Lessner S. M., Aoki H., Akram K., McKinney R. D., Ushio-Fukai M., Fukai T. Novel role of antioxidant-1 (Atox1) as a copper-dependent transcription factor involved in cell proliferation. Journal of Biological Chemistry, 2008, vol. 283, no. 14, pp. 9157–9168. https://doi.org/10.1074/jbc.M709463200
  8. Kolb V. G., Kamishnikov V. S. Determination of ceruloplasmin in serum by modified method of Ravina. In: Practical book in clinical chemistry. 2nd ed. Belarus, 1982, pp. 290–291. (in Russian)
  9. Kopylchuk G. P., Buchkovska I. M., Borschovetska N. L., Chopyk N. V. The activity of glutathione synthesis and conjugation enzymes in rat hepatocytes under conditions of low-protein diet and acute liver injury. Biological systems, 2014, vol. 6, no. 1, pp. 10–15. (in Ukrainian)
  10. Kopylchuk G. P., Voloshchuk O. M., Balandyuk O. V. Biochemical markers of the functional liver state in rats with toxic hepatitis under the conditions of germanium citrate administration. The Animal Biology, 2017, vol. 19, issue 1, pp. 59–64. (in Ukrainian) https://doi.org/10.15407/animbiol19.01.059
  11. Kumaratilake J. S. Chronic Copper Poisoning in Sheep: Liver Injury. Journal of Trace Element Analysis, 2014, vol. 3, no. 1, pp. 1–22. https://doi.org/10.7726/jtea.2014.1001
  12. Lin G., Luo D., Liu J., Wu X., Chen J., Huang Q., Su L., Zeng L., Wang H., Su Z. Hepatoprotective Effect of Polysaccharides Isolated from Dendrobium officinaleagainst Acetaminophen-Induced Liver Injury in Mice via Regulation of the Nrf2-Keap1 Signaling Pathway. Oxidative Medicine and Cellular Longevity, 2018, vol. 2018, pp. 1–10. https://doi.org/10.1155/2018/6962439
  13. Linder M. C., Hazegh-Azam M. Copper biochemistry and molecular biology. The American Journal of Clinical Nutrition, 1996, vol. 63, no. 5, pp. 797S–811S. DOI: 10.1093/ajcn/63.5.797.
  14. Lyman D. R., Clark L. J., Campbell K. L. Copper Accumulation in Wisconsin Holsteins with Indications of Oxidative Liver Damage. Journal of Veterinary Medicine and Research, 2015, vol. 2, no. 2, p. 1021.
  15. Manto M. Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration. Toxics, 2014, vol. 2, issue 2, pp. 327–345. https://doi.org/10.3390/toxics2020327
  16. Mounajjed T., Oxentenko A. S., Qureshi H., Smyrk T. C. Revisiting the Topic of Histochemically Detectable Copper in Various Liver Diseases With Special Focus on Venous Outflow Impairment. American Journal of Clinical Pathology, 2013, vol. 139, issue 1, pp. 79–86. https://doi.org/10.1309/AJCPDZR4OHDQNG3L
  17. 17. Musci G., Di Marco S., Bellenchi G. C., Calabrese L. Reconstitution of Ceruloplasmin by the Cu(I)-Glutathione Complex. Evidence for a role of Mg2+ and ATP The Journal of Biological Chemistry, 1996, vol. 271, issue 4, pp. 1972–1978. https://doi.org/10.1074/jbc.271.4.1972
  18. Reeves P. G., Nielsen F. H., Fahey G. C. AIN-93 Purified Diets for Laboratory Rodents: Final Report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76A Rodent Diet. The Journal of Nutrition, 1993, vol. 123, issue 11, pp. 19391951. https://doi.org/10.1093/jn/123.11.1939
  19. Roberts E. A., Sarkar B. Liver as a key organ in the supply, storage, and excretion of copper. The American Journal of Clinical Nutrition, 2008, vol. 88, issue 3, pp. 851S–854S. https://doi.org/10.1093/ajcn/88.3.851S
  20. Somanawat K., Thong-Ngam D., Klaikeaw N. Curcum-in attenuated paracetamol overdose induced hepatitis. World J. Gastroenterol., 2013, vol. 19, issue 12, pp. 1962–1967. https://doi.org/10.3748/wjg.v19.i12.1962
  21. Voloshchuk O. N., Kopylchuk G. P. An assessment of the ferrokinetic indices in rats with toxic hepatitis under the conditions of alimentary deprivation of protein. Experimental & clinical gastroenterology, 2016, vol. 10, no. 134, pp. 54–57. (in Russian)
  22. Voloshchuk O. N., Kopylchuk G. P. The State of the Adenyl Nucleotide System in the Liver of Rats with Toxic Hepatitis under Conditions of Protein Deficiency. Biophysics, 2017, vol. 62, issue 6, pp. 980–983. https://doi.org/10.1134/S0006350917060252
© 2016 Institute of Animal Biology