Antihypertensive Effect of Lactoferrin on Dexamethasone-Induced Hypertension in Rat

Document Type : Original Article (s)

Authors

1 Assistant Professor, Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences AND Isfahan Pharmaceutical Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 Student of Pharmacy, School of Pharmacy and Pharmaceutical Sciences AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Dexamethasone-induced hypertension is one of the animal models of hypertension. Lactoferrin is a natural iron-binding protein with proposed antihypertensive effects. In this study, the effect of chronic use of lactoferrin was investigated on dexamethasone-induced hypertension in rat and compared with captopril.Methods: In this experimental study, hypertension was induced by subcutaneously injection of dexamethasone (30 µg/kg/day) for 15 days in Wistar rat. Lactoferrin (300 mg/kg) and captopril (40 mg/kg) were orally given from the day 8 to 15. Systolic blood pressure was measured by tail cuff. Body weight was measured during experiment and thymus weight was detected as a marker of glucocorticoid activity at the end of study.Findings: Administration of dexamethasone increased systolic blood pressure (115.6 + 3.3 to 150.1 + 7.4 mmHg) and decreased body and thymus weight (P < 0.05). Chronic administration of lactoferrin and captopril for one week decreased systolic blood pressure (P < 0.01 for both). Lactoferrin also prevented body weight loss.Conclusion: The results indicated antihypertensive effect of lactoferrin on dexamethasone-induced hypertension. Further studies are suggested for finding the mechanism of lactoferrin in this model of hypertension. 

Keywords

References

  1. Ayub MY, Norazmir MN, Mamot S, Jeeven K, Hadijah H. Anti-hypertensive effect of pink guava (Psidium guajava) puree on spontaneous hypertensive rats. Int Food Res J 2010; 17(1): 89-96.
  2. Klumbiene J, Sileikiene L, Milasauskiene Z, Zaborskis A, Shatchkute A. The relationship of childhood to adult blood pressure: longitudinal study of juvenile hypertension in Lithuania. J Hypertens 2000; 18(5): 531-8.
  3. Murray CJL, Lopez AD. Global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. 1st ed. Cambridge, Mass: Harvard School of Public Health; 1996.
  4. Touyz RM. Molecular and cellular mechanisms in vascular injury in hypertension: role of angiotensin II. Curr Opin Nephrol Hypertens 2005; 14(2): 125-31.
  5. Burke V, Beilin LJ, Cutt HE, Mansour J, Wilson A, Mori TA. Effects of a lifestyle programme on ambulatory blood pressure and drug dosage in treated hypertensive patients: a randomized controlled trial. J Hypertens 2005; 23(6): 1241-9.
  6. Badyal DK, Lata H, Dadhich AP. Animal models of hypertension and effect of drugs. Indian J Pharmacol 2003; 35(6): 349-62.
  7. Rajashree S, Puvanakrishnan R. Dexamethasone induced alterations in enzymatic and nonenzymatic antioxidant status in heart and kidney of rats. Mol Cell Biochem 1998; 181(1-2): 77-85.
  8. Ong SLH, Zhang Y, Whitworth JA. Mechanisms of dexamethasone-induced hypertension. Curr Hypertens Rev 2009; 5(1): 61-74.
  9. Walker BR, Best R, Shackleton CH, Padfield PL, Edwards CR. Increased vasoconstrictor sensitivity to glucocorticoids in essential hypertension. Hypertension 1996; 27(2): 190-6.
  10. Schanbacher FL, Goodman RE, Talhouk RS. Bovine mammary lactoferrin: implications from messenger ribonucleic acid (mRNA) sequence and regulation contrary to other milk proteins. J Dairy Sci 1993; 76(12): 3812-31.
  11. van der Strate BW, Beljaars L, Molema G, Harmsen MC, Meijer DK. Antiviral activities of lactoferrin. Antiviral Res 2001; 52(3): 225-39.
  12. Oztas YE, Ozgunes N. Lactoferrin: a multifunctional protein. Adv Mol Med 2005; 1(4): 149–54.
  13. Rodriguez-Franco DA, Vazquez-Moreno L, Ramos-Clamont MG. Antimicrobial mechanisms and potential clinical application of lactoferrin. Rev Latinoam Microbiol 2005; 47(3-4): 102-11. [In Spanish].
  14. Conneely OM. Antiinflammatory activities of lactoferrin. J Am Coll Nutr 2001; 20(5 Suppl): 389S-95S.
  15. Hayashida K, Takeuchi T, Ozaki T, Shimizu H, Ando K, Miyamoto A, et al. Bovine lactoferrin has a nitric oxide-dependent hypotensive effect in rats. Am J Physiol Regul Integr Comp Physiol 2004; 286(2): R359-R365.
  16. Actor JK, Hwang SA, Kruzel ML. Lactoferrin as a natural immune modulator. Curr Pharm Des 2009; 15(17): 1956-73.
  17. Valenti P, Antonini G. Lactoferrin: an important host defence against microbial and viral attack. Cell Mol Life Sci 2005; 62(22): 2576-87.
  18. Brock JH. The physiology of lactoferrin. Biochem Cell Biol 2002; 80(1): 1-6.
  19. Hayashida K, Takeuchi T, Shimizu H, Ando K, Harada E. Novel function of bovine milk-derived lactoferrin on antinociception mediated by mu-opioid receptor in the rat spinal cord. Brain Res 2003; 965(1-2): 239-45.
  20. Norrby K, Mattsby-Baltzer I, Innocenti M, Tuneberg S. Orally administered bovine lactoferrin systemically inhibits VEGF(165)-mediated angiogenesis in the rat. Int J Cancer 2001; 91(2): 236-40.
  21. Ruiz-Gimenez P, Burguete MaC, Castello-Ruiz M, Marcos JF, Salom JB, Valles S, et al. Bovine lactoferrin pepsin hydrolysate exerts inhibitory effect on angiotensin I-converting enzyme-dependent vasoconstriction. Int Dairy J 2007; 17(10): 1212-5.
  22. Ruiz-Gimenez P, Salom JB, Marcos JF, Valles S, Martinez-Maqueda D, et al. Antihypertensive effect of a bovine lactoferrin pepsin hydrolysate: Identification of novel active peptides. Food Chem 2012; 131(1): 266–73.
  23. Fernandez-Musoles R, Lopez-Diez JJ, Torregrosa G, Valles S, Alborch E, Manzanares P, et al. Lactoferricin B-derived peptides with inhibitory effects on ECE-dependent vasoconstriction. Peptides 2010; 31(10): 1926-33.
  24. Hu L, Zhang Y, Lim PS, Miao Y, Tan C, McKenzie KU, et al. Apocynin but not L-arginine prevents and reverses dexamethasone-induced hypertension in the rat. Am J Hypertens 2006; 19(4): 413-8.
  25. Morgan T, Griffiths C, Delbridge L. Interaction of ACE inhibitors and AT(1)-receptor blockers on maximum blood pressure response in spontaneous hypertensive rats. J Renin Angiotensin Aldosterone Syst 2002; 3(1): 16-8.
  26. Ong SL, Vickers JJ, Zhang Y, McKenzie KU, Walsh CE, Whitworth JA. Role of xanthine oxidase in dexamethasone-induced hypertension in rats. Clin Exp Pharmacol Physiol 2007; 34(5-6): 517-9.
  27. Wallerath T, Witte K, Schafer SC, Schwarz PM, Prellwitz W, Wohlfart P, et al. Down-regulation of the expression of endothelial NO synthase is likely to contribute to glucocorticoid-mediated hypertension. Proc Natl Acad Sci U S A 1999; 96(23): 13357-62.
  28. Mulder AM, Connellan PA, Oliver CJ, Morris CA, Stevenson LM. Bovine lactoferrin supplementation supports immune and antioxidant status in healthy human males. Nutr Res 2008; 28(9): 583-9.
  29. Maneva A, Taleva B, Maneva L. Lactoferrin-protector against oxidative stress and regulator of glycolysis in human erythrocytes. Z Naturforsch C 2003; 58(3-4): 256-62.
  30. Konishi M, Iwasa M, Yamauchi K, Sugimoto R, Fujita N, Kobayashi Y, et al. Lactoferrin inhibits lipid peroxidation in patients with chronic hepatitis C. Hepatol Res 2006; 36(1): 27-32.
  31. Wakabayashi H, Kurokawa M, Shin K, Teraguchi S, Tamura Y, Shiraki K. Oral lactoferrin prevents body weight loss and increases cytokine responses during herpes simplex virus type 1 infection of mice. Biosci Biotechnol Biochem 2004; 68(3): 537-44.
Journal of Isfahan Medical School
Volume 31, Issue 245 - Serial Number 245
May and June 2013
Pages 1096-1104

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History

  • Receive Date: 20 July 2013
  • Revise Date: 08 May 2024
  • Accept Date: 06 April 2022

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