Phytothérapie

, Volume 11, Issue 6, pp 339–347

La Glisodin®, un extrait de melon, atténue l’apoptose des cardiomyocytes via la suppression du stress oxydant cardiaque au cours du diabète chronique expérimental

Article original Pharmacognosie

Résumé

Nous avons cherché à vérifier si l’atténuation du stress oxydatif lié au diabète pourrait diminuer le processus de la mort des cellules cardiaques. Notre étude a montré que l’apoptose cardiaque est semblable à une des réponses cellulaires majeures au diabète: induite par un stress oxydatif. La Glisodin®, une association de SOD de melon et de protéine de blé, également un puissant antioxydant, a freiné le développement de la cardiomyopathie diabétique. Nos résultats montrent une réduction significative des TUNEL-positifs dans les cardiomyocytes, observée chez le groupe diabétique traité par la Glisodin®. On a observé une diminution significative de la teneur en glutathion réduit, de l’activité de la SOD et de la catalase dans le cœur de rats diabétiques accompagnée par une augmentation des concentrations plasmatiques des LPO en comparaison aux rats traités par Glisodin®. Le traitement des rats diabétiques par la Glisodin® a rétabli l’augmentation de l’activité de la LDH et de la CPK exprimée chez les rats non traités. En conclusion, nos résultats suggèrent que l’atténuation de l’apoptose des cellules cardiaques par la Glisodin® assoie son effet préventif contre le développement de la cardiomyopathie diabétique. Toutefois, cet effet est principalement médié par une action antioxydante suppressive du stress oxydatif plutôt que par une action hypoglycémiante.

Mots clés

Diabète Cœur Apoptose Stress oxydant Glisodin® Rat 

Glisodin®, a melon extract that attenuates cardiac cell death via suppression of oxidative stress in the heart of Wistar rat with streptozotocin-induced diabetes

Abstract

We aimed to test whether attenuation of cardiac cell death can prevent diabetic cardiomyopathy. Our study showed that cardiac apoptosis as a major cellular response to diabetes is induced by hyperglycemia-derived oxidative stress. Glisodin® as a potent antioxidant prevents the development of diabetic cardiomyopathy. Eight weeks after STZ treatment, cardiac apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP labeling (TUNEL) assay. Oxidative stress in the heart tissue was evaluated by measuring GSH content, LPO level, and catalase and SOD activities. Cardiomyopathy was evaluated by measuring LDH and CPK activities. Our results show a significant reduction in diabetesinduced increases in TUNEL-positive cells was observed in a Glisodin® treatment group. A significant decrease of reduced glutathione content, superoxide dismutase, and catalase activities in the heart of diabetic rats accompanied by increased LPO plasma levels, but not in Glisodin®-treated rats, was observed. LDH and CPK activities as biomarkers of cardiomyopathy were decreased in Glisodin®-treated diabetic rats compared to diabetic-controlled rats. In conclusion, our results suggest that attenuation of cardiac cell death by Glisodin® treatment results in a significant prevention of the development of diabetic cardiomyopathy. This process is mediated by the antioxidant effect of Glisodin® to suppress oxidative stress in the heart.

Keywords

Diabetes Heart Cell death Oxidative stress Glisodin® Rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Références

  1. 1.
    Aebi H (1983) Catalase. In: Methods in enzymatic analysis (Ed. Bergmer HU), Vol. 3 Academic press, New York, pp. 276–286Google Scholar
  2. 2.
    Aliciguzel Y, Ozen I, Aslan M, Karayalcin U (2003) Activities of xanthine oxidoreductase ant antioxidant enzymes in different tissues of diabetic rats. J Lab Clin Med 142(3): 172–176PubMedCrossRefGoogle Scholar
  3. 3.
    An D, Rodrigues B (2006) Role of changes in cardiac metabolism in development of diabetic cardiomyopathy. Am J Physiol-Heart Circ Physiol 291: 1489–1506CrossRefGoogle Scholar
  4. 4.
    Artwohl M, Roden M, Waldhausl W, et al. (2004) Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells. FASEB J 18:146–148PubMedGoogle Scholar
  5. 5.
    Awaji Y, Hashimoto H, Matsui Y, et al. (1990) Isoenzyme profiles of creatine kinase, lactate dehydrogenase and aspartate aminotransferase in the diabetic heart: comparison with hereditary and catecholamine cardiomyopathies. Cardiovasc Res 24: 547–554PubMedCrossRefGoogle Scholar
  6. 6.
    Baumgartner-Parzer SM, Wagner L, Pettermann M, et al. (1995) Highglucose-triggered apoptosis in cultured endothelial cells. Diabetes 44: 1323–1327PubMedCrossRefGoogle Scholar
  7. 7.
    Beauchamps C, Fridovich L (1971) Superoxide dismutase: improved assays and assay applicable to acrylamide gels. Anal Biochem 44: 276–287CrossRefGoogle Scholar
  8. 8.
    Berry C, Hamilton CA, Brosnan MJ, et al. (2000) Investigation into the sources of superoxide in human blood vessels: angiotensin II increases superoxide production in human internal mammary arteries. Circulation 101: 2206–2212PubMedCrossRefGoogle Scholar
  9. 9.
    Bonnefont-Rousselot D (2002) Glucose and reactive oxygen species. Current Opinion in Clinical Nutrition Metabolic Care 5: 561–568PubMedCrossRefGoogle Scholar
  10. 10.
    Bowie A, O’Neill LAJ (2000) Oxidative stress and nuclear factor kB activation. Biochem Pharmacol 59: 7–11CrossRefGoogle Scholar
  11. 11.
    Christopher CL, Mathuram LN, Genitta G, et al. (2003) Omega-3 polyunsaturated fatty acids inhibit the accumulation of PAS — positive material in the myocardium of STZ-diabetic wistar rats. Int J Cardiol 88: 183–190PubMedCrossRefGoogle Scholar
  12. 12.
    Clemente MG, De Virgiliis S, Kang JS, et al. (2003) Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut 52: 218–223PubMedCrossRefGoogle Scholar
  13. 13.
    Chu N, Speigelman D, Hotamilsgil GS, et al. (2001) Plasma insulin, leptin and soluble TNF receptors levels in relation to obesity-related atherogenic and thrombogenic cardiovascular disease risk factors among men. Atherosclerosis 157: 495–503PubMedCrossRefGoogle Scholar
  14. 14.
    Cnop M, Hannaert JC, Hoorens A, et al. (2001) Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation. Diabetes 50: 1771–1777PubMedCrossRefGoogle Scholar
  15. 15.
    Dandona P, Thusu K, Cook S, et al. (1996) Oxidative damage to DNA in diabetes mellitus. Lancet 347: 444–445PubMedCrossRefGoogle Scholar
  16. 16.
    Das S, Vasisht S, Snehalata M, et al. (2000) Correlation between total antioxidant status and lipid peroxidation in hypercholesterolemia. Curr Sci 78: 486Google Scholar
  17. 17.
    Ezpeleta I, Arangoa MA, Irache JM, et al. (1999) Preparation of Ulex europaeus lectin-gliadin nanoparticle conjugates and their interaction with gastrointestinal mucus. Int J Pharm 191: 25–32PubMedCrossRefGoogle Scholar
  18. 18.
    Fasano A, Not T, Wang W, et al. (2000) Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet 355: 1518–1519PubMedCrossRefGoogle Scholar
  19. 19.
    Fiordaliso F, De Angelis N, Bai A, et al. (2007) Effect of beta-adrenergic and renin-angiotensin system blockade on myocyte apoptosis and oxidative stress in diabetic hypertensive rats. Life Sci 81: 951–959PubMedCrossRefGoogle Scholar
  20. 20.
    Fiordaliso F, Bianchi R, Staszewsky L, et al. (2004). Antioxidant treatment attenuates hyperglycemia-induced cardiomyocyte death in rats. J Mol Cell Cardiol 37: 959–968PubMedCrossRefGoogle Scholar
  21. 21.
    Fiordaliso F, Li B, Latini R, et al. (2000). Myocyte death in streptozotocin-induced diabetes in rats in angiotensinII dependent. Lab Invest 80: 513–527PubMedCrossRefGoogle Scholar
  22. 22.
    Frustaci A, Kajstura, J, Chimenti C, et al. (2000) Myocardial cell death in human diabetes. Circ Res 87: 1123–1132PubMedCrossRefGoogle Scholar
  23. 23.
    Grundy SM, Benjamin IJ, Burke GL, et al. (1999). Diabetes and cardiovascular disease: A statement for healthcare professionals from the American Heart Association. Circulation 100: 1134–1146PubMedCrossRefGoogle Scholar
  24. 24.
    Joanny Menvielle-Bourg F (2005) La superoxyde dismutase, puissant antioxydant naturel, désormais disponible par voie orale. Phytothérapie 3: 118–121CrossRefGoogle Scholar
  25. 25.
    Kajstura J, Fiordaliso F, Andreoli AM, et al. (2001) IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin II-mediated oxidative stress. Diabetes 50: 1414–1424PubMedCrossRefGoogle Scholar
  26. 26.
    Kang YJ (2001) Molecular and cellular mechanisms of cardiotoxicity. Environ Health Perspect 109(Suppl 1): 27–34PubMedCentralPubMedGoogle Scholar
  27. 27.
    Li N, Karin M (1999) Is NF-kB the sensor of oxidative stress? FASEB J 13: 1137–1143PubMedGoogle Scholar
  28. 28.
    Li S, Li X, Rozanski GJ (2003) Regulation of glutathione in cardiac myocytes. J Mol Cell Cardiol 35: 1145–1152PubMedCrossRefGoogle Scholar
  29. 29.
    Mauguet MC, Legrand J, Brujes L, et al. (2002) Gliadin matrices for microencapsulation processes by simple coacervation method. J Microencapsul 19: 377–384PubMedCrossRefGoogle Scholar
  30. 30.
    Montilla PL, Vargas JF, Tunez IF, et al. (1998) Oxidative stress in diabetic rats induced by streptozotocin: preventive effects of melatonin. J Pineal Res 25: 94–100PubMedCrossRefGoogle Scholar
  31. 31.
    Oberley LW, Spitz DR (1985) Assay of peroxide dismutase using nitroblue tetrazolium. In: Greenwald RA (ed) Handbook of methods for oxygen radical research. CRC Press, Boca Raton, pp. 217–220Google Scholar
  32. 32.
    Ohkawa H, Oshishi N, Yagi K (1979) Assay for lipid peroxydation in animal tissues by thiobarbituric acid reaction. Anal Biochem 95: 351–358PubMedCrossRefGoogle Scholar
  33. 33.
    Ouali K, Trea F, Toumi L, et al. (2007) L’hespéridine, un antioxydant flavonoïde qui diminue le stress oxydatif et prévient les malformations foetales au cours du diabète gestationnel expérimental. Phytothérapie 5: 204–209CrossRefGoogle Scholar
  34. 34.
    Paolisso G, Tataranni PA, Foley JE, et al. (1995) A high concentration of fasting plasma non-esterified is fatty acids a risk factor for the development of NIDDM. Diabetologia 38: 1213–1217PubMedCrossRefGoogle Scholar
  35. 35.
    Pon Velayutham A, Kuruvimalai Ekambaram S, Periasamy S, Chennam Srinivasulu S (2007) Green tea attenuates diabetes induced Maillard-type fluorescence and collagen cross-linking in the heart of streptozotocin diabetic rats. Pharmacol Res 55: 433–440CrossRefGoogle Scholar
  36. 36.
    Renard D, Robert P, Lavenant L, et al. (2002) Biopolymeric colloidal carriers for encapsulation or controlled release applications. Int J Pharm 242: 163–166PubMedCrossRefGoogle Scholar
  37. 37.
    Rodrigues B, Cam MC, Jian K, et al. (1997) Differential effects of streptozotocin-induced diabetes on cardiac lipoprotein lipase activity. Diabetes 46(8): 1346–1353PubMedCrossRefGoogle Scholar
  38. 38.
    Rodrigues B, Cam MC, McNeill JH (1995) Myocardial substrate metabolism: Implications for diabetic cardiomyopathy. J Mol Cell Cardiol 27: 169–179PubMedCrossRefGoogle Scholar
  39. 39.
    Schreck R, Baeuerle PA (1991) Reactive oxygen intermediates as apparently widely used messengers in the activation of NF-kB transcription factor and HIV-1. Trend Cell Biol 1: 32–42CrossRefGoogle Scholar
  40. 40.
    Shizukuda Y, Reyland ME, Buttrick PM (2002) Protein kinase C delta modulates apoptosis induced by hyperglycemia in adult ventricular myocytes. Am J Physiol Heart Circ Physiol 282: 1625–1634Google Scholar
  41. 41.
    Srinivasan S, Stevens M, Wiley JW (2000) Diabetic peripheral neuropathy: Evidence for apoptosis and associated mitochondrial dysfunction. Diabetes 49: 1932–1938PubMedCrossRefGoogle Scholar
  42. 42.
    Swynghedauw B (1999) Molecular mechanisms of myocardial remodelling Physiol Rev 79: 215–262PubMedGoogle Scholar
  43. 43.
    Tanaka Y, Gleason CE, Tran PO, et al. (1999) Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants. Proc Natl Acad Sci 96: 10857–10862PubMedCrossRefGoogle Scholar
  44. 44.
    Vouldoukis I, Lacan D, Kamate C, et al. (2004) Antioxidant and antiinflammatory properties of a Cucumis melo LC. extract rich in superoxide dismutase activity. J Ethnopharmacol 94: 67–75PubMedCrossRefGoogle Scholar
  45. 45.
    Vouldoukis I, Conti M, Krauss P, et al. (2004) Supplementation with gliadin-combined plant superoxide dismutase extract promotes antioxidant defences and protects against oxidative stress. Phytother Res 18: 957–962PubMedCrossRefGoogle Scholar
  46. 46.
    Wang W, Uzzau S, Goldblum SE, Fasano A (2000) Human zonulin, a potential modulator of intestinal tight junctions J Cell Sci 113(Pt 24): 4435–4440PubMedGoogle Scholar
  47. 47.
    Weckbecker G, Cory JG (1988) Ribonucleotide reductase activity and growth of glutathione depleted mouse leukaemia LI210 cells in vitro. Cancer Let 40: 257–264CrossRefGoogle Scholar
  48. 48.
    Wolff SP, Dean RT (1987) Glucose autooxidation and protein modification. Biochem J 245: 243–250PubMedGoogle Scholar
  49. 49.
    Wu TG, Li W, Lin Z, Wang Le (2008) Effects of folic acid on cardiac myocyte apoptosis in rats with streptozotocin-induced diabetes mellitus. Cardiovasc Drugs Ther 22: 299–304PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag France 2013

Authors and Affiliations

  1. 1.Laboratoire Emmaluniversité Badji-Mokhtar-AnnabaEl Hajar-AnnabaAlgérie
  2. 2.Laboratoire d’anapathologieUPHEl TarefAlgérie

Personalised recommendations