The aim of this study was to define the effects of diet containing the same mineral content of mineral salt or amino acid chelate, and diet containing various levels of Cu amino acid chelate on liver histomorphometry in growing rats. Male Wistar rats were used in the 12th week experiment. The control group (n = 12) was fed standard diet, which provided Cu in an inorganic form at the level required for rats. The experimental animals were divided into four groups (each n = 12) depending on different levels (100%, 75%, 50%, 25% covered daily demand) of Cu supplementation in chelated form. Cu content was determined in the liver tissue and blood plasma. Immunohistochemical staining with caspase-3 antibody was performed. Microscopic assessment of the liver structure indicated that Cu supplementation did not change the liver architecture. However, histomorphometric analysis revealed a significant increase in the number of nuclei, total cell number, and multinucleated hepatocytes in rats supplemented with the organic form of Cu at the level of 25% compared with the control group. There was a considerable increase in the number of apoptotic cells and ballooning degeneration of hepatocytes, especially in groups supplemented with organic form of Cu covering the daily demand in 100% and 75%, in comparison to control group. Moreover, there was no Cu deposition in the liver and changes in Cu content in blood. Cu provided in the diet in organic form covering an amount of its minimum daily demand in 25% appears to be the least harmful with regard to the liver. It indicates that there is a need to establish the level of diet supplementation with Cu amino acid chelates.
1. Andersen O.: Chemical and biological considerations in the treatment of metal intoxications by chelating agents. Mini Rev Med Chem 2004, 4, 11-21.
2. Arakeri G., Brennan P.A.: Dietary copper: A novel predisposing factor for oral submucous fibrosis? Med Hypotheses 2013, 80, 241 -243.
3. Arredondo M., Nunez M.T.: Iron and copper metabolism. Mol Aspects Med 2005, 26, 313-327.
4. Brewer G.J.: Copper toxicity in the general population. Clin Neurophysiol 2010, 121, 459-460.
5. Broderius M., Prohaska J.R.: Differential impact of copper deficiency in rats on blood cuproproteins. Nutr Res 2009, 29, 494-502.
6. Ding X., Xie H., Kang Y.J.: The significance of copper chelators in clinical and experimental application. J Nutr Biochem 2011, 22, 301-310.
7. Ettle T., Schlegel P., Roth X., Investigations on iron bioavailability of different sources and supply levels in piglets. J Anim Physiol Anim Nutr (Berlin) 2008, 92, 30-45.
8. Feng J., Ma W.Q., Xu Z.R., Heb J.X., Wang Y.Z. Liu J.X.: The effect of iron glycine chelate on tissue mineral levels, fecal mineral concentration, and liver antioxidant enzyme activity in weanling pigs. Anim Feed Sci Technol 2009, 150, 106-113.
9. Feng J., Ma W.Q., Xua Z.R., Wang Y.Z. Liu J.X.: Effects of iron glycine chelate on growth, haematological and immunological characteristics in weanling pigs. Anim Feed Sci Technol 2007, 134, 261 -272.
11. Guo R., Henry P.R., Holwerda R.A., Cao J., Littell R.C., Miles R.D., Ammerman C.B. Chemical characteristics and relative bioavailability of supplemental organics copper sources for poultry. J Anim Sci 2001, 79, 1132-1141.
12. Lesson S.: A new look at trace mineral nutrition of poultry: can we reduce the environmental burden of poultry mature? In: Biotechnology in the feed industry, Proc. 19th Alltech’s Annual Symp., Nottingham University Press, Nottingham, UK, 2003, pp. 125-129.
13. López de Romana D., Olivares M., Uauy R., Araya M.: Risks and benefits of copper in light of new insights of copper homeostasis. J Trace Elem Med Biol 2011, 25, 3-13.
14. Luo X.G., JI F., Lin Y.X., Steward F.A., Lu L., Liu B., Yu S.X.: Effects of dietary supplementation with copper sulfate or tribasic copper chloride on broiler performance, relative copper bioavailability, and oxidation stability of vitamin E in feed. Poult Sci 2005, 84, 888-893.
15. Ma W.Q., Sun H.Y., Zhou J., Wu J., Feng J.: Effects of iron glycine chelate on growth, tissue mineral concentrations, Fecal mineral excretion, and liver antioxidant enzyme activities in broilers. Biol Trace Elem Res 2012, 149, 204-211.
16. Mao S., Medeiros D.M., Hamlin R.L.: Marginal cooper and high fat diet produce alteration in electrocardiograms and cardiac ultrastructure in male rats. Nutrition 1999, 11/12, 890-898.
17. Megahed M.A., Hassanin K.M.A., Youssef I.M I., Elfghi A.B.A., Amin K.A.: Alterations in plasma lipids, glutathione and homocysteine in relation to dietary copper in rats. J Invest Biochem 2013, DOI: 10.5455/jib.20130716075753.
18. Männer K., Simon O., Schlegel P.: Effects of different iron, manganese, zinc and copper sources (sulfates, chelates, glycinates) on their bioavailability in early weaned piglets. In: 9. Tagung Schweine - und Geflügelernährung. Edited by Rodehutscord M., Universität Halle-Wittenberg, Germany, 2006.
19. Peňa M.M.O., Lee J., Thiele D.J.: A delicate balance: homeostatic control of copper uptake and distribution. J Nutr 1999, 1129, 1251-1260.
20. Pineda O., Ashmead H.D.: Effectiveness of treatment of iron-deficiency anemia in infants and young children with ferrous bis-glycinate chelate. Nutrition 2001, 17, 381-384.
21. Reeves P.G., DeMars L.C.: Copper deficiency reduces iron absorption and biological half-life in male rats. J Nutr 2004, 134, 1953-1957.
22. Reeves P.G., Ralston N.V.C., Idso J.P., Lukaski H.C.: Contrasting and cooperative effects of copper and iron deficiencies in male rats fed different concentrations of manganese and different sources of sulfur amino acids in an AIN-93G-based diet. J Nutr 2004, 134, 416-125.
23. Mehta R., Templeton D.M., ‘Brien P.J.O.: Mitochondrial involvement in genetically determined transition metal toxicity. Copper toxicity. Chem Biol Interact 2006, 163, 77-85.
24. Rinaldi A.C.: Meeting report - copper research at the top. Biometals 2000, 13, 9-13.
25. Roberts E.A., Michael L.: Schilsky diagnosis and treatment of Wilson Disease: An Update. Hepatology 2008, 47, 2089-2111.
26. SCAN Scientific Committee for Animal Nutrition: Opinion on the use of copper in feedingstuff. European Commission Publication, Brussels, 2003.
27. Sadhra S., Wheatley A.D., Cross H.J.: Dietary exposure to cooper in the European Union and its assessment for EU regulatory risk assessment. Sci Total Environ 2007, 374, 223234.
28. Skrivan M., Sknvanová V., Marounek M.: Effects of dietary zinc, iron and copper in layer feed on distribution of these elements in eggs, liver, excreta, soil and herbage. Poult Sci 2005, 84, 1570-1575.
29. Suriawinata A.A., Thung S.N.: Liver pathology an atlas and concise guide. Demos Medical, New York, 2011.
30. Swiątkiewicz S., Koreleski J., Hong D.Q. The bioavailability of zinc from inorganic and organic sources in broiler chickens as affected by addition of phytase. J Anim Feed Sci 2001, 10, 317328.
31. Tamim N., Angel R.: Phytate phosphorous hydrolysis as influenced by dietary calcium and micro-mineral source in broiler diets. J Agricult Food Chem 2003, 51, 4687-4693.
32. Tomaszewska E., Dobrowolski P., Puzio I.: Postnatal administration of 2-oxoglutaric acid improves the intestinal barrier affected by the prenatal action of dexamethasone in pigs. Nutrition 2012, 28, 190-196.