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Diosgenin attenuates inflammatory response induced by myocardial reperfusion injury: role of mitochondrial ATP-sensitive potassium channels

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Abstract

Reperfusion injury is one of the main reasons of cardiac disease morbidity. Phytopharmaceuticals are gaining importance in modern medicine of cardioprotection because of their multiplex capacity. The aim of this study was to investigate the effect of diosgenin on the inflammatory response induced by myocardial ischemia and reperfusion injury and the role of mitochondrial ATP-sensitive potassium (mitoKATP) channels in this regard. Wistar rats (250–300 g) were used in this study. The Langendorff-perfused hearts of animals were subjected to a 30-min global ischemia followed by a 90-min reperfusion. The lactate dehydrogenase (LDH) release was measured by spectrophotometry. The levels of inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6 in the supernatant of heart’s left ventricle were measured using an enzyme-linked immunosorbent assay rat specific ELISA kit. The LDH release into the coronary effluent during reperfusion was significantly decreased, and cardiac contractility significantly improved by diosgenin preadministration as compared with those of control or Cremophor-EL (solvent of diosgenin) groups (398 ± 48 vs. 665 ± 65 or 650 ± 73 ml/min) (P < 0.01). Administration of diosgenin before the main ischemia significantly reduced the levels of IL-6 (P < 0.05), IL-1β, and TNF-α (P < 0.01) in the reperfusion phase of diosgenin-treated hearts as compared with untreated control hearts. Inhibition of mitoKATP channels by 5-hydroxydecanoate significantly reverses the cardioprotective effects of diosgenin (P < 0.05). The findings of the present study indicate that preconditioning with diosgenin may induce cardioprotective effect against reperfusion injury through reducing the production of inflammatory mediators and activating the mitoKATP channels.

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References

  1. Alberici LC, Paim BA, Zecchin KG, Mirandola SR, Pestana CR, Castilho RF, Vercesi AE, Oliveira HC (2013) Activation of the mitochondrial ATP-sensitive K+ channel reduces apoptosis of spleen mononuclear cells induced by hyperlipidemia. Lipid Health Dis 12(87):1–9

    Google Scholar 

  2. Badalzadeh R, Mohammadi M, Najafi M, Ahmadiasl N, Farajnia S, Ebrahimi H (2012) The additive effects of ischemic postconditioning and cyclosporine-A on nitric oxide activity and functions of diabetic myocardium injured by ischemia/reperfusion. J Cardiovasc Pharmacol Ther 17(2):181–189

    Article  CAS  PubMed  Google Scholar 

  3. Bonvini RF, Hendiri T, Camenzind E (2005) Inflammatory response post-myocardial infarction and reperfusion: a new therapeutic target? Eur Heart J Suppl 7(Supplement I):I27–I36

    Article  CAS  Google Scholar 

  4. Bulua AC, Simon A, Maddipati R, Pelletier M, Park M, Kim KY, Sack MN, Kastner DL, Siege RM (2011) Mitochondrial reactive oxygen species promote production of pro-inflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). JEM 208(3):519–533

    Article  CAS  Google Scholar 

  5. Facundo HT, de Paula JG, Kowaltowski AJ (2007) Mitochondrial ATP-sensitive K+ channels are redox-sensitive pathways that control reactive oxygen species production. Free Radical Biol Med 42(7):1039–1048

    Article  CAS  Google Scholar 

  6. Gonga G, Qinb Y, Huanga W, Zhouc S, Wub X, Yangc X, Yinlan Z, Li D (2010) Protective effects of diosgenin in the hyperlipidemic rat model and in human vascular endothelial cells against hydrogen peroxide-induced apoptosis. Chem Biol Interact 184:366–375

    Article  Google Scholar 

  7. Halestrap A, Clarke SJ, Khaliulin I (2007) The role of mitochondria in protection of the heart by preconditioning. Biochimica Biophysica Acta 1767:1007–1031

    Article  CAS  Google Scholar 

  8. Hirai S, Uemura T, Mizoguchi N, J-Y L, Taketani K, Nakano Y, Hoshino S, Tsuge N, Narukami T, Yu R, Takahashi N, Kawada T (2010) Diosgenin attenuates inflammatory changes in the interaction between adipocytes and macrophages. Mol Nutr Food Res 54:797–804

    Article  CAS  PubMed  Google Scholar 

  9. Jaswal JS, Gandhi M, Finegan BA, Dyck JR, Clanachan AS (2007) Inhibition of p38 MAPK and AMPK restores adenosine-induced cardioprotection in hearts stressed by antecedent ischemia by altering glucose utilization. Am J Physiol Heart Circ Physiol 293:H1107–H1114

    Article  CAS  PubMed  Google Scholar 

  10. Jayachandran KS, Vasanthi HR, Rajamanickam GV (2009) Antilipoperoxidative and membrane stabilizing effect of diosgenin, in experimentally induced myocardial infarction. Mol Cell Biochem 327:203–210

    Article  CAS  PubMed  Google Scholar 

  11. Jiang WL, Fu FH, Xu BM, Tian JW, Zhu HB, Hou J (2010) Cardioprotection with forsythoside B in rat myocardial ischemia-reperfusion injury: relation to inflammation response. Phytomedicine 17:635–639

    Article  CAS  PubMed  Google Scholar 

  12. Jung DH, Park HJ, Byun HE, Park YM, Kim TW, Kim BO, Um SH, Pyo S (2010) Diosgenin inhibits macrophage-derived inflammatory mediators through downregulation of CK2, JNK, NF-κB and AP-1 activation. Int Immunopharmacol 10:1047–1054

    Article  CAS  PubMed  Google Scholar 

  13. Kim TH, Lee SM (2010) The effects of ginseng total saponin, panaxadiol and panaxatriol on ischemia/reperfusion injury in isolated rat heart. Food Chem Toxicol 48:1516–1520

    Article  CAS  PubMed  Google Scholar 

  14. Leger DY, Liagre B, Beneytout JL (2006) Role of MAPKs and NF-κB in diosgenin-induced megakaryocytic differentiation and subsequent apoptosis in HEL cells. Int J Oncol 28(1):201–207

    CAS  PubMed  Google Scholar 

  15. Lísias K, Dias G, Azevedo Correia ND, Gonçalves PK, Barbosa-Filho JM, Marques KV, Araújo IG, Silva DF, Guedes DN, Anjos NM, Bendhack LM, Medeiros IA (2007) Mechanisms involved in the vasodilator effect induced by diosgenin in rat superior mesenteric artery. Eur J Pharmacol 574:172–178

    Article  Google Scholar 

  16. Lutz J, Thürme K, Heemann U (2010) Anti-inflammatory treatment strategies for ischemia/reperfusion injury in transplantation. J Inflam 7:27

    Article  Google Scholar 

  17. Ma A, Qi S, Chen H (2008) Antioxidant therapy for prevention of inflammation, ischemic reperfusion injuries and allograft rejection. Cardiovasc Hematol Agents Med Chem 6:20–43

    Article  CAS  PubMed  Google Scholar 

  18. McAnuff MA, Harding WW, Omoruyi FO, Jacobs H, Morrison EY, Asemota HN (2005) Hypoglycemic effects of steroidal sapogenins isolated from Jamaican bitter yam, dioscorea polygonoides. Food Chem Toxicol 43:1667–1672

    Article  CAS  PubMed  Google Scholar 

  19. McCully J, Levitsky S (2003) The mitochondrial K-ATP channel and cardioprotection. Ann Thorac Surg 75:S667–S673

    Article  PubMed  Google Scholar 

  20. Nossuli TO, Lakshminarayanan V, Baumgarten G, Taffet E, Ballantyne CM, Michae LH, Entman ML (2000) A chronic mouse model of myocardial ischemia-reperfusion: essential in cytokine studies. Am J Physiol Heart Circ Physiol 278:H1049–H1055

    CAS  PubMed  Google Scholar 

  21. Pari L, Monisha P, MedJalaludeen A (2012) Beneficial role of diosgenin on oxidative stress in aorta of streptozotocin induced diabetic rats. Eur J Pharmacol 691:143–150

    Article  CAS  PubMed  Google Scholar 

  22. Perrelli MG, Pagliaro P, Penna C (2011) Ischemia/reperfusion injury and cardioprotective mechanisms: role of mitochondria and reactive oxygen species. World J Cardiol 3(6):186–200

    Article  PubMed Central  PubMed  Google Scholar 

  23. Piper HM, Meuter K, Schäfer C (2003) Cellular mechanisms of ischemia-reperfusion injury. Ann Thorac Surg 75:644–648

    Article  Google Scholar 

  24. Sanada S, Komuro I, Kitakaze M (2011) Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures. Am J Physiol Heart Circ Physiol 301:H1723–H1741

    Article  CAS  PubMed  Google Scholar 

  25. Schmidt MR, Smerup M, Konstantinov IE, Shimizu M, Li J, Cheung M, White PA, Kristiansen SB, Sorensen K, Dzavik V, Redington AN, Kharbanda RK (2007) Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic preconditioning. Am J Physiol Heart Circ Physiol 292:H1883–H1890

    Article  CAS  PubMed  Google Scholar 

  26. Son IS, Kim JH, Sohn HY, Son KH, Kim JS, Kwon CS (2007) Antioxidative and hypolipidemic effects of diosgenin, a steroidal saponin of yam (dioscorea spp.) on high-cholesterol fed rats. Biosci Biotechnol Biochem 7:3063–3071

    Article  Google Scholar 

  27. Song J-X, Ma L, Kou JP, Yang YB (2012) Diosgenin reduces leukocytes adhesion and migration linked with inhibition of intercellular adhesion molecule-1 expression and NF-κB p65 activation in endothelial cells. Chin J Nat Med 10(2):0142–0149

    Article  CAS  Google Scholar 

  28. Turer AT, Hill JA (2010) Pathogenesis of myocardial ischemia-reperfusion injury and rationale for therapy. Am J Cardiol 106(3):360–368

    Article  PubMed Central  PubMed  Google Scholar 

  29. Yadav VR, Prasad S, Sung B, Kannappan R, Aggarwal BB (2010) Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer. Toxins 2:2428–2466

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Yellon DM, Hausenloy DJ (2007) Myocardial reperfusion injury. N Engl J Med 357:1121–1135

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study has been supported with a financial grant from the Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz-Iran.

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There is no conflict of interest in this study.

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Correspondence to Reza Badalzadeh.

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Ebrahimi, H., Badalzadeh, R., Mohammadi, M. et al. Diosgenin attenuates inflammatory response induced by myocardial reperfusion injury: role of mitochondrial ATP-sensitive potassium channels. J Physiol Biochem 70, 425–432 (2014). https://doi.org/10.1007/s13105-014-0320-9

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  • DOI: https://doi.org/10.1007/s13105-014-0320-9

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