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Biochemical and Morphological Alterations in Hearts of Copper-Deficient Bovines

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Abstract

Copper deficiency is an important disease of cattle that produces several clinical signs and lesions, due to alterations in copper-dependent enzymes. One of the organs affected by this deficiency is the heart (falling disease), but nevertheless, these cardiac lesions have not been extensively studied in bovines. The aim of this work was to propose a possible pathogenic mechanism for cardiac lesions in cattle affected by copper deficiency. Because of the possible existence of oxidative distress caused by low levels of copper-zinc-superoxide dismutase and cytochrome oxidase, ultrastructural and histological lesions have been evaluated in the heart of bovines in which a Cu deficiency had been induced using high molybdenum and sulfur levels in the diet. Our results indicated that copper deficiency produces significant damage in myocardium with high levels of lipid oxidation and a significant reduction in copper-zinc-superoxide dismutase activity leading to an oxidative distress situation. However, cytochrome oxidase activity was not significantly reduced. Histological observation revealed a significant increase in the amount of connective tissue, enlarged basement membranes of myocytes, and numerous Anichkov cells, in the hearts of deficient animals. Ultrastructural observation showed a significant enhancement in the mitochondrial volume density, with presence of lesions such as swelling and cristae disruption. We conclude that copper deficiency in bovines causes morphological lesions in the heart due to an oxidative damage produced by copper-dependent enzyme alterations.

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References

  1. Underwood EJ, Suttle NF (1999) The mineral nutrition of livestock, 3rd edn. CABI Publishing, UK

    Book  Google Scholar 

  2. Suttle NF (1986) Problems in the diagnosis and anticipation of trace elements deficiencies in grazing livestock. Vet Rec 119:148–452

    Article  CAS  Google Scholar 

  3. Bennetts HW, Beck AB, Harley R (1948) The pathogenesis of Falling disease. Aust Vet J 24(9):237–244

    Article  Google Scholar 

  4. Bennetts HW, Harley R, Evans ST (1942) Studies on copper deficiency of cattle: the fatal termination (“Falling disease”). Aust Vet J 18(2):50–63

    Article  CAS  Google Scholar 

  5. Mills CF, Dalgarno AC, Wenham G (1976) Biochemical and pathological changes in tissues of Fressian cattle during the experimental induction of copper deficiency. Br J Nutr 35(3):309–331

    Article  CAS  Google Scholar 

  6. Suttle NF, Angus KW (1976) Experimental copper deficiency in the calf. J Comp Pathol 86(4):595–608

    Article  CAS  Google Scholar 

  7. Fields M (1999) Role of trace elements in coronary heart disease. Br J Nutr 81(2):85–86

    Article  CAS  Google Scholar 

  8. Klevay LM (2000) Cardiovascular disease from copper deficiency-a history. J Nutr 130(2):489S–492S

    Article  CAS  Google Scholar 

  9. Davidson J, Medeiros DM, Hamlin RL, Jenkins JE (1993) Submaximal, aerobic exercise training exacerbates the cardiomyopathy of postweanling Cu-depleted rats. Biol Trace Elem Res 38(3):251–272

    Article  CAS  Google Scholar 

  10. Werman MJ, David R (1996) Lysyl oxidase activity, collagen cross-links and connective tissue ultrastructure in the heart of copper-deficient male rats. J Nutr Biochem 7(8):437–444

    Article  CAS  Google Scholar 

  11. Lear PM, Prohaska JR (1997) Atria and ventricles of copper-deficient rats exhibit similar hypertrophy and similar altered biochemical characteristics. Proc Soc Exp Biol Med 215(4):377–385

    Article  CAS  Google Scholar 

  12. Johnson WT, Anderson CM (2008) Cardiac cytochrome c oxidase activity and contents of subunit 1 and 4 are altered in offspring by low prenatal copper intake. J Nutr 138(7):1269–1273

    Article  CAS  Google Scholar 

  13. Johnson WT, Newman SM (2007) Hearts in adult offspring of copper-deficient dams exhibit decreased cytochrome c oxidase activity, increased mitochondrial hydrogen peroxide generation and enhanced formation of intracellular residual bodies. J Nutr Biochem 18(2):97–104

    Article  CAS  Google Scholar 

  14. Medeiros DM, Liao Z, Hamlin RL (1991) Copper deficiency in a genetically hypertensive cardiomyopathic rat: electrocardiogram, functional and ultrastructural aspects. J Nutr 121(7):1026–1034

    Article  CAS  Google Scholar 

  15. Davidson J, Medeiros DM, Hamlin RL (1992) Cardiac ultrastructural and electrophysiological abnormalities in postweanling copper-restricted and copper-repleted rats in the absence of hypertrophy. J Nutr 122:1566–1575

    Article  CAS  Google Scholar 

  16. Wildman RE, Hopkins R, Failla ML, Medeiros DM (1995) Marginal copper-restricted diets produce altered cardiac ultrastructure in the rat. Exp Biol Med 210(1):43–49

    Article  CAS  Google Scholar 

  17. National Research Council (2000) Nutrient requirements of beef cattle. National Academic of Science-National Research Council, USA

    Google Scholar 

  18. Postma GC, Minatel L, Olivares RWI, Schapira A, Dallorso ME, Carfagnini JC (2013) Bactericidal activity of lachrymal secretion and complement system in copper deficient bovines. Biol Trace Elem Res 153(1–3):178–183

    Article  CAS  Google Scholar 

  19. Engle TE, Spears JW (2000) Effects of dietary copper concentration and source on performance and copper status of growing and finishing steers. J Anim Sci 78(9):2446–2451

    Article  CAS  Google Scholar 

  20. Suvarna SK, Layton C, Bancroft JD (2013) Bancroft’s theory and practice of histological techniques, 7th edn. Elsevier, UK

    Google Scholar 

  21. Gibson-Corley KN, Olivier AK, Meyerholz DK (2013) Principles for valid histopathologic scoring in research. Vet Pathol 50(6):1007–1015

    Article  CAS  Google Scholar 

  22. Crouser ED, Julian MW, Dorinsky PM (1999) Ileal VO2-DO2 alterations induced by endotoxin correlate with severity of mitochondrial injury. Am J Respir Crit Care Med 160(4):1347–1353

    Article  CAS  Google Scholar 

  23. Boveris A, Lores Arnaiz S, Bustamante J, Alvarez S, Valdez LB, Boveris AD, Navarro A (2002) Pharmacological regulation of mitochondrial nitric oxide synthase. Methods Enzymol 359:328–339

    Article  CAS  Google Scholar 

  24. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59(3):527–605

    Article  CAS  Google Scholar 

  25. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    CAS  PubMed  Google Scholar 

  26. Flohé L, Ötting F (1984) Superoxide dismutase assays. Methods Enzymol 105:93–104

    Article  Google Scholar 

  27. Zaobornyj T, Valdez LB, Iglesias DE, Gasco M, Gonzales G, Boveris A (2009) Mitochondrial nitric oxide metabolism during rat heart adaptation to high altitude: effect of sildenafil, L-NAME and L-arginine treatments. Am J Physiol Heart Circ Physiol 296:1741–1747

    Article  Google Scholar 

  28. Scarlata E, O’Flaherty C, Carfagnini JC (1998) Lipoperoxidación y lesión muscular inducida por ejercicio intenso en ratas. Rev Med Vet 79(5):444–448

    Google Scholar 

  29. Yagi K (1976) A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med 15(2):212–216

    Article  CAS  Google Scholar 

  30. Aitken RJ, Harkiss D, Buckingham D (1993) Relationship beween iron-catalyzed lipid peroxidation potential and human sperm function. J Reprod Fertil 98(1):257–265

    Article  CAS  Google Scholar 

  31. Ginn PE, Mansell JEKL, Rakich PM (2007) Copper deficiency. In: Maxie MG (ed) Jubb, Kennedy and Palmer’s pathology of domestic animals, vol. 2, 5th edn. Elsevier, St. Louis, p 603

    Google Scholar 

  32. McGavin MD, Zachary JF (2007) Pathologic basis of veterinary disease, 4th edn. Mosby Elsevier, St. Louis

    Google Scholar 

  33. Sylvén C, Lin L, Kallner A, Jansson E (1989) Regional distribution of citrate synthase and lactate dehydrogenase isoenzymes in the bovine heart. Acta Physiol Scand 136(3):331–338

    Article  Google Scholar 

  34. Bol'shakova GB (1984) Origin of Anichkov’s cells in the myocardium. Bul Exp Biol Med 97(3):354–356

    Google Scholar 

  35. Psaltis PJ, Carbone A, Nelson A, Lau DH, Manavis J, Finnie J, Teo KS, Mackenzie L, Sanders P, Gronthos S, Zannettino ACW, Worthley SG (2008) An ovine model of toxic, nonischemic cardiomyopathy-assessment by cardiac magnetic resonance imaging. J Card Fail 14(9):785–795

    Article  Google Scholar 

  36. Robinson WF, Robinson NA (2016) Myocardial necrosis. In: Maxie MG (ed) Jubb, Kennedy and Palmer’s pathology of domestic animals, vol. 3, 6th edn. Elsevier, St. Louis, p 37

    Google Scholar 

  37. Fell BF, Farmer LJ, Farquharson C, Bremner I, Graca DS (1985) Observations on the pancreas of cattle deficient in copper. J Comp Pathol 95(4):573–590

    Article  CAS  Google Scholar 

  38. Fell BF, Farquharson C, Riddoch GI (1987) Kidney lesions in copper-deficient rats. J Comp Pathol 97(2):187–196

    Article  CAS  Google Scholar 

  39. Farquharson C, Robins SP (1991) Immunolocalization of collagen types I, III and IV, elastin and fibronectin within the heart of normal and copper-deficient rats. J Comp Pathol 104(3):245–255

    Article  CAS  Google Scholar 

  40. Li Y, Wang L, Schuschke DA, Zhou Z, Saari J, Kang YJ (2005) Marginal dietary copper restriction induces cardiomyopathy in rats. J Nutr 135(9):2130–2136

    Article  CAS  Google Scholar 

  41. Sies H (2017) Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: oxidative eustress. Redox Biol 11:613–619

    Article  CAS  Google Scholar 

  42. Wakabayashi T (2002) Megamitochondria formation-physiology and pathology. J Cell Mol Med 6(4):497–538

    Article  CAS  Google Scholar 

  43. Tandler B, Fujioka H, Hoppel CL, Haldar SM, Jain MK (2015) Megamitochondria in cardiomyocytes of a knockout (Klf15−/−) mouse. Ultrastruct Pathol 39(5):336–339

    Article  Google Scholar 

  44. Zeng H, Saari JT, Johnson WT (2007) Copper deficiency decreases complex IV but not complex I, II, III, or V in the mitochondrial respiratory chain in rat heart. J Nutr 137(1):14–18

    Article  CAS  Google Scholar 

  45. Tatarkova Z, Kuka S, Racay P et al (2011) Effects of aging on activities of mitochondrial electron transport chain complexes and oxidative damage in rat heart. Physiol Res 60(2):281–289

    CAS  PubMed  Google Scholar 

  46. Rosca MG, Vazquez EJ, Kerner J, Parland W, Chandler MP, Stanley W, Sabbah HN, Hoppel CL (2008) Cardiac mitochondria in heart failure: decrease in respirasomes and oxidative phosphorylation. Cardiovasc Res 80(1):30–39

    Article  CAS  Google Scholar 

  47. Szabó C, Ischiropoulos H, Radi R (2007) Peroxynitrite: biochemistry, pathophysiology and development of therapeutics. Nat Rev Drug Discov 6(8):662–680

    Article  Google Scholar 

  48. Strassburger M, Bloch W, Sulyok S, Schüller J, Keist AF, Schmidt A, Wenk J, Peters T, Wlaschek M, Lenart J, Krieg T, Hafner M, Kümin A, Werner S, Müller W, Scharffetter-Kochanek K (2005) Heterozygous deficiency of manganese superoxide dismutase results in severe lipid peroxidation and spontaneous apoptosis in murine myocardium in vivo. Free Radic Biol Med 38(11):1458–1470

    Article  CAS  Google Scholar 

  49. Yang SJ, Keen CL, Lanoue L, Rucker RB, Uriu-Adams JY (2007) Low nitric oxide: a key factor underlying copper-deficiency teratogenicity. Free Radic Biol Med. 43(12):1639–1648

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Cátedra de Patología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires (UBA), Avenida San Martín 5285, C1427CWO, Buenos Aires, Argentina

    Roberto Walter Israel Olivares, Gabriela Cintia Postma, Andrea Schapira, Pablo Daniel Gazzaneo & Leonardo Minatel

  2. Facultad de Farmacia y Bioquímica, Cátedra de Fisicoquímica, Universidad de Buenos Aires, Buenos Aires, Argentina

    Dario Ezequiel Iglesias & Laura Beatriz Valdez

  3. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Bioquímica y Medicina Molecular (IBIMOL), Buenos Aires, Argentina

    Dario Ezequiel Iglesias & Laura Beatriz Valdez

  4. Facultad de Ciencias Veterinarias, Cátedra de Química Biológica, Universidad de Buenos Aires, Buenos Aires, Argentina

    Elizabeth Breininger

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  1. Roberto Walter Israel Olivares
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  2. Gabriela Cintia Postma
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  7. Pablo Daniel Gazzaneo
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Correspondence to Roberto Walter Israel Olivares.

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All protocols for this study were approved by the Institutional Experimental Animal Care and Use Committee of University of Buenos Aires, Faculty of Veterinary Science (CICUAL).

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The authors declare that they have no conflict of interest.

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Olivares, R.W.I., Postma, G.C., Schapira, A. et al. Biochemical and Morphological Alterations in Hearts of Copper-Deficient Bovines. Biol Trace Elem Res 189, 447–455 (2019). https://doi.org/10.1007/s12011-018-1476-x

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