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Antilipoperoxidative and membrane stabilizing effect of diosgenin, in experimentally induced myocardial infarction

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Abstract

Altered membrane integrity has been suggested as a major factor in the development of cellular injury during myocardial necrosis. The present study was designed to investigate the effect of diosgenin on lysosomal hydrolases, membrane-bound enzymes, and electrolytes during isoproterenol (ISO)-induced myocardial necrosis in rats. Animals were pretreated with DIOS (80 mg/kg) for a period of 35 days. Myocardial infarction was experimentally induced with ISO (85 mg/kg) twice at 24 h interval. Experimental myocardial infarction was evidenced with marked elevation of creatine kinase-MB (CK-MB) in serum with concomitant increase in lipid peroxidation (plasma thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HP)). Activity of lysosomal hydrolases (β-glucuronidase, β-N-acetyl glucosaminidase, β-d-galactosidase, cathepsin D, and acid phosphatase) was found to be increased in serum and heart tissue of ISO-alone treated animals. DIOS (80 mg/kg) pretreated groups showed significant decrease in CK-MB, lipid peroxidation, and lysosomal hydrolases activity. The membrane-bound enzymes such as Ca2+-ATPase and Mg2+-ATPase activity was increased and Na+/K+-ATPase activity was decreased in the heart tissues of ISO-alone treated animals. These enzyme alterations lead to the change in the electrolytes content such as sodium, potassium, and calcium in the heart tissue. However, DIOS (80 mg/kg) pretreatment reversed the membrane-bound enzymes activity and thereby maintained the normal electrolyte concentration. These results suggest the protective action of diosgenin in ISO-induced myocardial infarction. The salubrious effect observed in this study might be due to the antioxidant and membrane stabilizing potential of diosgenin.

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References

  1. Hoffstein S, Gennaro DE, Weissmann G et al (1975) Cytochemical localization of lysosomal enzyme activity in normal and ischemic dog myocardium. Am J Pathol 79:193–206

    PubMed  CAS  Google Scholar 

  2. Yogeeta SK, Gnanapragasam A, Senthilkumar S et al (2006) Synergestic salubrious effect of ferulic acid and ascorbic acid on membrane bound phosphatases and lysosomal hydrolase during experimental myocardial infarction in rats. Life Sci 80:258–263. doi:10.1016/j.lfs.2006.09.012

    Article  PubMed  CAS  Google Scholar 

  3. Ravichandran LV, Puvanakrishnan R, Joseph KT (1991) Influence of isoproterenol-induced myocardial infarction on certain glycohydrolases and cathepsins in rats. Biochem Med Metab Biol 45:6–15. doi:10.1016/0885-4505(91)90003-4

    Article  PubMed  CAS  Google Scholar 

  4. Decker RS, Poole AR, Griffin EE et al (1977) Altered distribution of lysosomal cathepsin-D in ischemic myocardium. J Clin Invest 59:911–921. doi:10.1172/JCI108713

    Article  PubMed  CAS  Google Scholar 

  5. Wexler BC (1978) Myocardial infarction in young vs old male rats; pathophysiologic changes. Am Heart J 96:70–80. doi:10.1016/0002-8703(78)90128-X

    Article  PubMed  CAS  Google Scholar 

  6. Kumari SS, Jayadeep A, Kumar JSS et al (1989) Effects of carnitine on malondialdehyde, taurine, glutathione levels in heart of rats subjected to myocardial stress by isoproterenol. Indian J Exp Biol 27:134–137

    Google Scholar 

  7. Sathish V, Ebenazer KK, Devaki T (2003) Synergistic effect of nicorandil and amlodipine on lysosomal hydrolases during experimental myocardial infarction in rats. Biomed Pharmacother 57:309–313. doi:10.1016/S0753-3322(03)00036-2

    Article  PubMed  CAS  Google Scholar 

  8. Todd GL, Cullan GE, Cullam GM (1980) Isoproterenol induced myocardial necrosis and membrane permeability alteration in the isolated perfused rabbit heart. Exp Mol Pathol 33:43–54. doi:10.1016/0014-4800(80)90006-4

    Article  PubMed  CAS  Google Scholar 

  9. Nirmala C, Puvanakrishnan R (1996) Protective role of curcumin against isoproterenol induced myocardial infarction in rats. Mol Cell Biochem 159:85–93. doi:10.1007/BF00420910

    Article  PubMed  CAS  Google Scholar 

  10. Banerjee SK, Maulik SK (2002) Effect of garlic on cardiovascular disorders: a review. Nutr J 1:4. doi:10.1186/1475-2891-1-4

    Article  PubMed  Google Scholar 

  11. Chiang C, Way T, Tsai S et al (2007) Diosgenin, a naturally occurring steroid, suppresses fatty acid synthase expression in HER2-overexpressing breast cancer cells through modulating Akt, mTOR and JNK phosphorylation. FEBS Lett 581:5735–5742. doi:10.1016/j.febslet.2007.11.021

    Article  PubMed  CAS  Google Scholar 

  12. McAnuff MA, Omoruyi FO, Morrison EY et al (2002) Plasma and liver lipid distributions in streptozotocin-induced diabetic rats fed sapogenin extract of the Jamaican bitter yam (Dioscorea polygonoides). Nutr Res 22:1427–1434. doi:10.1016/S0271-5317(02)00457-8

    Article  CAS  Google Scholar 

  13. McAnuff MA, Harding WW, Omoruyi FO et al (2005) Hypoglycemic effects of steroidal sapogenins isolated from Jamaican bitter yam, Dioscorea polygonoides. Food Chem Toxicol 43:1667–1672. doi:10.1016/j.fct.2005.05.008

    Article  PubMed  CAS  Google Scholar 

  14. Yamada T, Hoshino M, Hayakawa T et al (1997) Dietary diosgenin attenuates subacute intestinal inflammation associated with indomethacin in rats. Am J Physiol 273:G355–G364

    PubMed  CAS  Google Scholar 

  15. Melo PS, De-Azevedo MBM, Zullo MAT et al (2004) Cytotoxicity of the phytosterol diosgenin and its derivatives in rat cultured hepatocytes and V79 fibroblasts. Hum Exp Toxicol 23:487–493. doi:10.1191/0960327104ht474oa

    Article  PubMed  CAS  Google Scholar 

  16. Son IS, Kim JH, Sohn HY et al (2007) Antioxidative and hypolipidemic effects of diosgenin, a steroidal saponin of yam (Dioscorea spp.) om high-cholesterol fed rats. Biosci Biotechnol Biochem 71:3063–3071. doi:10.1271/bbb.70472

    Article  PubMed  CAS  Google Scholar 

  17. Rajadurai M, Prince PSM (2006) Preventive effect of naringin on lipid peroxides and antioxidants in isoproterenol-induced cardiotoxicity in Wistar rats: biochemical and histopathological evidences. Toxicology 228:259–268. doi:10.1016/j.tox.2006.09.005

    Article  PubMed  CAS  Google Scholar 

  18. Nichans WG, Samuelson D (1968) Formation of malondialdehyde from phospholipids arrachidonate during microsomal lipid peroxidation. Eur J Biochem 6:126–130. doi:10.1111/j.1432-1033.1968.tb00428.x

    Article  Google Scholar 

  19. Jiang ZY, Hunt JV, Wolff SP (1992) Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low-density lipoprotein. Anal Biochem 202:384–389. doi:10.1016/0003-2697(92)90122-N

    Article  PubMed  CAS  Google Scholar 

  20. Kawai Y, Anno K (1971) Mucopolysaccharide-degrading enzymes from the liver of the squid, Ommastrephes sloani pacificus. I. Hyaluronidase. Biochim Biophys Acta 242:428–436

    PubMed  CAS  Google Scholar 

  21. Moore JC, Morris JE (1982) A simple automated colorimetric method for determination of N-acetyl-β-d-glucosaminidase. Ann Clin Biochem 19:157–159

    PubMed  CAS  Google Scholar 

  22. Conchie J, Gelman AL, Levy GA (1967) Inhibition of glycosidases by aldonolactones of corresponding configuration. The C-4 and C-6 specificity of β-glucosidase and β-galactosidase. Biochem J 103:609–615

    PubMed  CAS  Google Scholar 

  23. Sapolsky AI, Altman RD, Howell DS (1973) Cathepsin-D activity in normal and osteoarthritic human cartilage. Fed Proc 32:1489–1493

    PubMed  CAS  Google Scholar 

  24. King J (1965) The hydrolases-acid and alkaline phosphatases. In: Van D (ed) Practical clinical enzymology. Nostrand Company Ltd, London, pp 191–208

    Google Scholar 

  25. Bonting SL (1970) Membrane and ion transport. In: Presence of enzyme systems in mammalian tissues. Wiley Interscience, London, pp 257–263

  26. Hjerten S, Pan H (1983) Purification and characterization of two forms of low affinity Ca2+-ATPase from erythrocyte membrane. Biochim Biophys Acta 728:281–288. doi:10.1016/0005-2736(83)90480-7

    Article  PubMed  CAS  Google Scholar 

  27. Ohnishi T, Suzuki T, Suzuki Y, Ozawa K (1982) A comparative study of plasma membrane Mg2+-ATPase activities in normal, regenerating and malignant cells. Biochim Biophys Acta 684:67–74. doi:10.1016/0005-2736(82)90050-5

    Article  PubMed  CAS  Google Scholar 

  28. Ballentine R, Burford DD (1957) Determination of metals. In: Colowick SP, Kalpan NO (ed) Methods in enzymology vol. 3. Academic Press, New York, pp 1002–1035

  29. Morin LG (1974) Direct colorimetric determination of serum calcium with o-cresolphthalein complexion. Am J Clin Pathol 61:114–117

    PubMed  CAS  Google Scholar 

  30. Lowry OH, Rosebrough MJ, Farr AL et al (1951) Protein measurement with folin-phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  31. Whealthy AM, Thandroyen FT, Opie LH (1985) Catecholamine induced myocardial cell damage: catecholamines or adrenochrome. J Mol Cell Cardiol 17:349–359. doi:10.1016/S0022-2828(85)80134-6

    Article  Google Scholar 

  32. Hearse DJ (1979) Cellular damage during myocardial ischaemia: metabolic changes leading to enzyme leakage. In: Hearse DJ, De Leiris J, Losiance D (eds) Enzymes in cardiology. Wiley, New York, pp 1–21

    Google Scholar 

  33. Cohen G, Heikkila RE (1974) The generation of hydrogen peroxide, superoxide radical and hydroxyl radical by 6-hydroxydopamine, dialuric acid and related cytotoxic agents. J Biol Chem 249:2447–2452

    PubMed  CAS  Google Scholar 

  34. Thompson JA, Hess ML (1986) The oxygen free radical system: a fundamental mechanism in the production of myocardial necrosis. Prog Cardiovasc Dis 28:449–462. doi:10.1016/0033-0620(86)90027-7

    Article  PubMed  CAS  Google Scholar 

  35. McAnuff MA, Omoruyi FO, Morrison EY et al (2003) Hepatic function enzymes and lipid peroxidation in streptozotocin-induced diabetic rats fed bitter yam (Dioscorea polygonoides) steroidal sapogenin extract. Diabetol Croat 32:17–23

    Google Scholar 

  36. Fantone JC, Ward PA (1982) Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol 107:395–418

    PubMed  CAS  Google Scholar 

  37. Sudharsan PT, Mythili Y, Selvakumar E et al (2006) Lupeol and its ester ameliorate the cyclophosphamide provoked cardiac lysosomal damage studied in rat. Mol Cell Biochem 282:23–29. doi:10.1007/s11010-006-1169-1

    Article  PubMed  CAS  Google Scholar 

  38. Ravichandran LV, Puvanakrishnan R, Joseph KT (1990) Alterations in heart lysosomal stability in isoproterenol induced myocardial infarction in rats. Biochem Int 22:387–396

    PubMed  CAS  Google Scholar 

  39. Padmanabhan M, Prince PSM (2007) S-allylcysteine ameliorates isoproterenol-induced cardiotoxicity in rats by stabilizing cardiac mitochondrial and lysosomal enzymes. Life Sci 80:972–978. doi:10.1016/j.lfs.2006.11.028

    Article  PubMed  CAS  Google Scholar 

  40. Riccutti MA (1972) Myocardial lysosomal stability in the early stages of acute ischemic injury. Am J Cardiol 30:492–497. doi:10.1016/0002-9149(72)90039-2

    Article  Google Scholar 

  41. Decker RS, Wildenthal K (1978) Sequential lysosomal alterations during cardiac ischemia. II. Ultrastructural and cytochemical changes. Lab Invest 38:662–673

    PubMed  CAS  Google Scholar 

  42. Gubdjorson S, Hallgrimson J, Skuldottir G (1983) Properties of transport adenosine triphosphatase. In: Peter H, Geshaw GA, Paoethi R (eds) Arterial pollution. Plenum, New York, p 101

    Google Scholar 

  43. Trump BF, Bereezeky IK, Sato T et al (1984) Cell calcium, cell injury and cell death. Environ Health Perspect 57:281–287. doi:10.2307/3429928

    Article  PubMed  CAS  Google Scholar 

  44. Vajreswari W, Narayanareddy K (1992) Effect of dietary fats on some membrane bound enzyme activities, membrane lipid composition and fatty acid profiles of rat heart sarcolemma. Lipids 27:339–343. doi:10.1007/BF02536147

    Article  PubMed  CAS  Google Scholar 

  45. Mourelle M, Franco MT (1991) Erythrocytes defects precede the onset of CCl4 induced liver cirrohsis. Protection of siyymarin. Life Sci 48:1083–1090. doi:10.1016/0024-3205(91)90510-I

    Article  PubMed  CAS  Google Scholar 

  46. Jennings RB, Reimer KA, Steenbergen C (1986) Myocardial ischemia revisited. The osmolar load, membrane damage and reperfusion. J Mol Cell Cardiol 18:769–780. doi:10.1016/S0022-2828(86)80952-X

    Article  PubMed  CAS  Google Scholar 

  47. Sathish V, Ebenazer KK, Devaki T (2003) Biochemical changes on the cardioprotective effect of nicorandil and amlodipine during experimental myocardial infarction in rats. Pharmacol Res 48:565–570. doi:10.1016/S1043-6618(03)00223-8

    Article  PubMed  CAS  Google Scholar 

  48. Panagia V, Pierce GN, Dhalla KS et al (1985) Adaptive charges in subcellular calcium transport during catecholamine-induced cardiomyopathy. J Mol Cell Cardiol 17:411–420. doi:10.1016/S0022-2828(85)80140-1

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors are grateful to the Drugs and Pharmaceuticals Division, Dept. of Science and Technology, Govt. of India for providing Junior Research fellowship to the first author and Prof. R.Sethuraman, Vice-chancellor, SASTRA University for his support and encouragement during the course of this work.

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Correspondence to Hannah R. Vasanthi.

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Jayachandran, K.S., Vasanthi, H.R. & Rajamanickam, G.V. Antilipoperoxidative and membrane stabilizing effect of diosgenin, in experimentally induced myocardial infarction. Mol Cell Biochem 327, 203–210 (2009). https://doi.org/10.1007/s11010-009-0058-9

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