BioMetals

, Volume 22, Issue 2, pp 353–361 | Cite as

The effects of lactoferrin in a rat model of catecholamine cardiotoxicity

  • Přemysl Mladěnka
  • Vladimír Semecký
  • Zuzana Bobrovová
  • Petr Nachtigal
  • Jaroslava Vávrová
  • Magdaléna Holečková
  • Vladimir Palicka
  • Yvona Mazurová
  • Radomír Hrdina
Article

Abstract

Lactoferrin is recently under intense investigation because of its proposed several pharmacologically positive effects. Based on its iron-binding properties and its physiological presence in the human body, it may have a significant impact on pathological conditions associated with iron-catalysed reactive oxygen species (ROS). Its effect on a catecholamine model of myocardial injury, which shares several pathophysiological features with acute myocardial infarction (AMI) in humans, was examined. Male Wistar rats were randomly divided into four groups according to the received medication: control (saline), isoprenaline (ISO, 100 mg kg−1 s.c.), bovine lactoferrin (La, 50 mg kg−1 i.v.) or a combination of La + ISO in the above-mentioned doses. After 24 h, haemodynamic functional parameters were measured, a sample of blood was withdrawn and the heart was removed for analysis of various parameters. Lactoferrin premedication reduced some impairment caused by ISO (e.g. a stroke volume decrease, an increase in peripheral resistance and calcium overload). These positive effects were likely to have been mediated by the positive inotropic effect of lactoferrin and by inhibition of ROS formation due to chelation of free iron. The failure of lactoferrin to provide higher protection seems to be associated with the complexity of catecholamine cardiotoxicity and with its hydrophilic character.

Keywords

Lactoferrin Isoprenaline Iron chelators Reactive-oxygen species Iron Catecholamines 

References

  1. Abdallah FB, El Hage Chahine JM (2000) Transferrins: iron release from lactoferrin. J Mol Biol 303:255–266. doi:10.1006/jmbi.2000.4101 PubMedCrossRefGoogle Scholar
  2. Baker EN, Baker HM (2005) Molecular structure, binding properties and dynamics of lactoferrin. Cell Mol Life Sci 62:2531–2539. doi:10.1007/s00018-005-5368-9 PubMedCrossRefGoogle Scholar
  3. Baker EN, Anderson BF, Baker HM, Day CL, Haridas M, Norris GE, Rumball SV, Smith CA, Thomas DH (1994) Three-dimensional structure of lactoferrin in various functional states. Adv Exp Med Biol 357:1–12PubMedGoogle Scholar
  4. Bennett RM, Kokocinski T (1979) Lactoferrin turnover in man. Clin Sci (Lond) 57:453–460Google Scholar
  5. Berenshtein E, Vaisman B, Goldberg-Langerman C, Kitrossky N, Konijn AM, Chevion M (2002) Roles of ferritin and iron in ischemic preconditioning of the heart. Mol Cell Biochem 234–235:283–292. doi:10.1023/A:1015923202082 PubMedCrossRefGoogle Scholar
  6. Bolli R, Patel BS, Jeroudi MO, Li XY, Triana JF, Lai EK, McCay PB (1990) Iron-mediated radical reactions upon reperfusion contribute to myocardial “stunning”. Am J Physiol 259:H1901–H1911PubMedGoogle Scholar
  7. Britigan BE, Serody JS, Cohen MS (1994) The role of lactoferrin as an anti-inflammatory molecule. Adv Exp Med Biol 357:143–156PubMedGoogle Scholar
  8. Brock JH (2002) The physiology of lactoferrin. Biochem Cell Biol 80:1–6. doi:10.1139/o01-212 PubMedCrossRefGoogle Scholar
  9. Chagoya de Sanchez V, Hernandez-Munoz R, Lopez-Barrera F, Yanez L, Vidrio S, Suarez J, Cota-Garza MD, Aranda-Fraustro A, Cruz D (1997) Sequential changes of energy metabolism and mitochondrial function in myocardial infarction induced by isoproterenol in rats: a long-term and integrative study. Can J Physiol Pharmacol 75:1300–1311. doi:10.1139/cjpp-75-12-1300 PubMedCrossRefGoogle Scholar
  10. Coudray C, Pucheu S, Boucher F, Arnaud J, de Leiris J, Favier A (1994) Effect of ischemia/reperfusion sequence on cytosolic iron status and its release in the coronary effluent in isolated rat hearts. Biol Trace Elem Res 41:69–75. doi:10.1007/BF02917218 PubMedCrossRefGoogle Scholar
  11. Erga KS, Peen E, Tenstad O, Reed RK (2000) Lactoferrin and anti-lactoferrin antibodies: effects of ironloading of lactoferrin on albumin extravasation in different tissues in rats. Acta Physiol Scand 170:11–19. doi:10.1046/j.1365-201x.2000.00754.x PubMedCrossRefGoogle Scholar
  12. Fielding RA, Violan MA, Svetkey L, Abad LW, Manfredi TJ, Cosmas A, Bean J (2000) Effects of prior exercise on eccentric exercise-induced neutrophilia and enzyme release. Med Sci Sports Exerc 32:359–364. doi:10.1097/00005768-200002000-00015 PubMedCrossRefGoogle Scholar
  13. Gutteridge JM, Paterson SK, Segal AW, Halliwell B (1981) Inhibition of lipid peroxidation by the iron-binding protein lactoferrin. Biochem J 199:259–261PubMedGoogle Scholar
  14. Hasenfuss G (1998) Animal models of human cardiovascular disease, heart failure and hypertrophy. Cardiovasc Res 39:60–76. doi:10.1016/S0008-6363(98)00110-2 PubMedCrossRefGoogle Scholar
  15. Inoue H, Sakai M, Kaida Y, Kaibara K (2004) Blood lactoferrin release induced by running exercise in normal volunteers: antibacterial activity. Clin Chim Acta 341:165–172. doi:10.1016/j.cccn.2003.12.001 PubMedCrossRefGoogle Scholar
  16. Kalinowski DS, Richardson DR (2007) Future of toxicology-iron chelators and differing modes of action and toxicity: the changing face of iron chelation therapy. Chem Res Toxicol 20:715–720. doi:10.1021/tx700039c PubMedCrossRefGoogle Scholar
  17. Karle H, Hansen NE, Malmquist J, Karle AK, Larsson I (1979) Turnover of human lactoferrin in the rabbit. Scand J Haematol 23:303–312PubMedGoogle Scholar
  18. Kontoghiorghes GJ (2006) New chelation therapies and emerging chelating drugs for the treatment of iron overload. Expert Opin Emerg Drugs 11:1–5. doi:10.1517/14728214.11.1.1 PubMedCrossRefGoogle Scholar
  19. Kurose I, Yamada T, Wolf R, Granger DN (1994) P-selectin-dependent leukocyte recruitment and intestinal mucosal injury induced by lactoferrin. J Leukoc Biol 55:771–777PubMedGoogle Scholar
  20. Lentner C (1990) Geigy scientific tables. Ciba-Geigy, BaselGoogle Scholar
  21. Metz-Boutigue MH, Jolles J, Mazurier J, Schoentgen F, Legrand D, Spik G, Montreuil J, Jolles P (1984) Human lactotransferrin: amino acid sequence and structural comparisons with other transferrins. Eur J Biochem 145:659–676. doi:10.1111/j.1432-1033.1984.tb08607.x PubMedCrossRefGoogle Scholar
  22. Neri M, Cerretani D, Fiaschi AI, Laghi PF, Lazzerini PE, Maffione AB, Micheli L, Bruni G, Nencini C, Giorgi G, D’Errico S, Fiore C, Pomara C, Riezzo I, Turillazzi E, Fineschi V (2007) Correlation between cardiac oxidative stress and myocardial pathology due to acute and chronic norepinephrine administration in rats. J Cell Mol Med 11:156–170. doi:10.1111/j.1582-4934.2007.00009.x PubMedCrossRefGoogle Scholar
  23. Oseas R, Yang HH, Baehner RL, Boxer LA (1981) Lactoferrin: a promoter of polymorphonuclear leukocyte adhesiveness. Blood 57:939–945PubMedGoogle Scholar
  24. Paffett ML, Walker BR (2007) Vascular adaptations to hypoxia: molecular and cellular mechanisms regulating vascular tone. Essays Biochem 43:105–119. doi:10.1042/BSE0430105 PubMedCrossRefGoogle Scholar
  25. Parkkinen J, Sahlstedt L, von Bonsdorff L, Salo H, Ebeling F, Ruutu T (2006) Effect of repeated apotransferrin administrations on serum iron parameters in patients undergoing myeloablative conditioning and allogeneic stem cell transplantation. Br J Haematol 135:228–234. doi:10.1111/j.1365-2141.2006.06273.x PubMedCrossRefGoogle Scholar
  26. Plomteux G, Charlier C, Albert A, Farnier M, Pressac M, Vernet M, Paris M, Dellamonica C, Dezier JF (1987) Reference values of serum transferrin in newborn infants, children and adults. Ann Biol Clin (Paris) 45:622–629Google Scholar
  27. Raghuveer TS, McGuire EM, Martin SM, Wagner BA, Rebouche CJ, Buettner GR, Widness JA (2002) Lactoferrin in the preterm infants’ diet attenuates iron-induced oxidation products. Pediatr Res 52:964–972PubMedGoogle Scholar
  28. Reddy BR, Wynne J, Kloner RA, Przyklenk K (1991) Pretreatment with the iron chelator desferrioxamine fails to provide sustained protection against myocardial ischaemia-reperfusion injury. Cardiovasc Res 25:711–718. doi:10.1093/cvr/25.9.711 PubMedCrossRefGoogle Scholar
  29. Regoeczi E, Chindemi PA, Debanne MT, Prieels JP (1985) Lactoferrin catabolism in the rat liver. Am J Physiol 248:G8–G14PubMedGoogle Scholar
  30. Rona G (1985) Catecholamine cardiotoxicity. J Mol Cell Cardiol 17:291–306. doi:10.1016/S0022-2828(85)80130-9 PubMedCrossRefGoogle Scholar
  31. Santos-Silva A, Rebelo I, Castro E, Belo L, Catarino C, Monteiro I, Almeida MD, Quintanilha A (2002) Erythrocyte damage and leukocyte activation in ischemic stroke. Clin Chim Acta 320:29–35PubMedGoogle Scholar
  32. Shimmura S, Shimoyama M, Hojo M, Urayama K, Tsubota K (1998) Reoxygenation injury in a cultured corneal epithelial cell line protected by the uptake of lactoferrin. Invest Ophthalmol Vis Sci 39:1346–1351PubMedGoogle Scholar
  33. Spiller P, Webb-Peploe MM (1985) Blood flow. Eur Heart J 6(suppl C):11–18PubMedGoogle Scholar
  34. Sterba M, Popelova O, Simunek T, Mazurova Y, Potacova A, Adamcova M, Guncova I, Kaiserova H, Palicka V, Ponka P, Gersl V (2007) Iron chelation-afforded cardioprotection against chronic anthracycline cardiotoxicity: a study of salicylaldehyde isonicotinoyl hydrazone (SIH). Toxicology 235:150–166. doi:10.1016/j.tox.2007.03.020 PubMedCrossRefGoogle Scholar
  35. van Snick JL, Markowetz B, Masson PL (1977) The ingestion and digestion of human lactoferrin by mouse peritoneal macrophages and the transfer of its iron into ferritin. J Exp Med 146:817–827. doi:10.1084/jem.146.3.817 PubMedCrossRefGoogle Scholar
  36. Ward PA, Till GO, Kunkel R, Beauchamp C (1983) Evidence for role of hydroxyl radical in complement and neutrophil-dependent tissue injury. J Clin Invest 72:789–801. doi:10.1172/JCI111050 PubMedCrossRefGoogle Scholar
  37. Weinberg ED (2003) The therapeutic potential of lactoferrin. Expert Opin Investig Drugs 12:841–851. doi:10.1517/13543784.12.5.841 PubMedCrossRefGoogle Scholar
  38. Weinberg ED (2006) Therapeutic potential of iron chelators in diseases associated with iron mismanagement. J Pharm Pharmacol 58:575–584. doi:10.1211/jpp.58.5.0001 PubMedCrossRefGoogle Scholar
  39. Wolach B, Coates TD, Hugli TE, Baehner RL, Boxer LA (1984) Plasma lactoferrin reflects granulocyte activation via complement in burn patients. J Lab Clin Med 103:284–293PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Přemysl Mladěnka
    • 1
  • Vladimír Semecký
    • 2
  • Zuzana Bobrovová
    • 1
  • Petr Nachtigal
    • 2
  • Jaroslava Vávrová
    • 3
  • Magdaléna Holečková
    • 3
  • Vladimir Palicka
    • 3
  • Yvona Mazurová
    • 4
  • Radomír Hrdina
    • 1
  1. 1.Faculty of Pharmacy in Hradec Králové, Department of Pharmacology and ToxicologyCharles University in PragueHradec KraloveCzech Republic
  2. 2.Faculty of Pharmacy in Hradec Králové, Department of Biological and Medical SciencesCharles University in PragueHradec KraloveCzech Republic
  3. 3.Faculty of Medicine in Hradec Králové, Institute of Clinical Biochemistry and DiagnosticsCharles University in PragueHradec KraloveCzech Republic
  4. 4.Faculty of Medicine in Hradec Králové, Department of Histology and EmbryologyCharles University in PragueHradec KraloveCzech Republic

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