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Effects of pharmacological preconditioning by emodin/oleanolic acid treatment and/or ischemic preconditioning on mitochondrial antioxidant components as well as the susceptibility to ischemia-reperfusion injury in rat hearts

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Abstract

Using an ex vivo rat heart model of ischemia-reperfusion (I-R) injury, we examined the effect of pharmacological preconditioning by chronic treatment with emodin (EMD)/oleanolic acid (OA) at low dose (25 μ mol/kg/day × 15) and/or ischemic preconditioning (IPC) (4 cycles of 5 min ischemia followed by 5 min of reperfusion) on myocardial I-R injury. The results indicated that EMD/OA pretreatment, IPC, or their combinations (EMD+IPC and OA+IPC) protected against myocardial I-R injury, as assessed by lactate dehydrogenase leakage and contractile force recovery. The cardioprotection was associated with a differential enhancement in mitochondrial antioxidant components. The combined EMD/OA and IPC pretreatment produced cardioprotective action in a semi-additive manner. This suggested that EMD/OA pretreatment and IPC protected against myocardial I-R injury via a similar but not identical biochemical mechanism.

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Abbreviations

EMD:

emodin

GSH:

reduced glutathione

IPC:

ischemia preconditioning

I-R:

ischemia-reperfusion

LDH:

lactate dehydrogenase

OA:

oleanolic acid

Mn-SOD:

Mn-superoxide dismutase

α-TOC:

α -tocopherol

References

  1. Baines CP, Zhang J, Wang GW, Zheng YT, Xiu JX, Cardwell EM, Bolli R, Ping P: Mitochondrial PKCε and MAPK form signaling modules in the murine heart: enhanced mitochondrial PKCε-MAPK interactions and differential MAPK activation in PKCε-induced cardioprotection. Circ Res 90: 390–397, 2002

    Article  PubMed  CAS  Google Scholar 

  2. Ghosh S, Standen NB, Galinanes M: Preconditioning the human myocardium by simulated ischemia: Studies on the early and delayed protection. Cardiovasc Res 45: 339–350, 2000

    Article  PubMed  CAS  Google Scholar 

  3. Pain T, Yang XM, Critz SD, Yue Y, Nakano A, Liu GS, Heusche G, Cohen MV, Downey JM: Opening of mitochondrial K(ATP) channels triggers the preconditioned state by generating free radicals. Circ Res 87: 460–466, 2000

    PubMed  CAS  Google Scholar 

  4. Kloner R, Jennings R: Consequences of brief ischemia: Stunning, preconditioning and their clinical implications Part II. Circulation 104: 3158–3167, 2001

    PubMed  CAS  Google Scholar 

  5. Huang KC: The Pharmacology of Chinese Herbs. CRC Press, Boca Raton, Ann Arbor, London, Tokyo, pp 101–103, 1993

    Google Scholar 

  6. Liu J: Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 49: 57–68, 1995

    Article  PubMed  CAS  Google Scholar 

  7. Shi HY, Cheng SH, Chen CC, Lee H: Emodin inhibits the mutagenicity and DNA adducts induced by 1-nitropyrene. Mut Res 329: 205–212, 1995

    Google Scholar 

  8. Huang HC, Chu SH, Chao-Lee PD: Vasorelexants from Chinese herbs, emodin and scoparone, possess immunosuppressive properties. Eur J Pharmacol 198: 211–213, 1991

    Article  PubMed  CAS  Google Scholar 

  9. Marquina S, Maldonado N, Garduno-Ramirez ML, Aranda E, Villareal ML, Navarro V et al.: Bioactive oleanolic acid saponins and other constituents from roots of Viguiera decurrens. Phytochemistry 56: 93–97, 2001

    Article  PubMed  CAS  Google Scholar 

  10. Yim TK, Wu WK, Pak WF, Ko KM: Hepatoprotective action of an oleanolic acid-enriched extract of Ligustrum lucidum fruits is mediated through an enhancement on hepatic glutathione regeneration capacity in mice. Phytother Res 15: 589–592, 2001

    Article  PubMed  CAS  Google Scholar 

  11. Yim TK, Wu WK, Mak DHF, Ko KM: Myocardial protective effect of an anthraquinone-containing extract of Polygonum multiflorum ex vivo. Planta Med 64: 607–611, 1998

    PubMed  CAS  Google Scholar 

  12. Du Y, Ko KM: Effects of emodin treatment on mitochondrial ATP generation capacity and antioxidant components as well as susceptibility to ischemia-reperfusion injury in rat hearts: Single versus multiple doses and gender difference. Life Sci 77: 2770–2782, 2005

    Article  PubMed  CAS  Google Scholar 

  13. Du Y, Ko KM: Oleanolic acid protects against myocardial ischemia-reperfusion injury by enhancing mitochondrial antioxidant mechanism mediated by glutathione and α-tocopherol in rats. Planta Med (in press)

  14. Li PC, Mak DHF, Poon MKT, Ip SP, Ko KM: Myocardial protective effect of Sheng Mai San (SMS) and a lignan-enriched extract of Fructus Schisandrae, in vivo and ex vivo. Phytomedicine III: 217–221, 1996

  15. Evans WH: Isolation and characterization of membranes and cell organelles. In: Rickwood D (ed). Preparative Centrifugation: A practical approach. Oxford University Press, New York, 1992, pp. 233–270

    Google Scholar 

  16. Griffith OW: Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106: 207–12, 1980

    Article  PubMed  CAS  Google Scholar 

  17. Sadrzadeh SM, Nanji AA, Meydani M: Effect of chronic ethanol feeding on plasma and liver alpha- and gamma-tocopherol levels in normal and vitamin E-deficient rats. Relationship to lipid peroxidation. Biochem Pharmacol 47: 2005–2010, 1994

    CAS  Google Scholar 

  18. McCord JM, Fridovich I: Superoxide dismutase. An enzyme function for erythrocuprein (Hemocuprein). J Biol Chem 244: 6049–6055, 1969

    PubMed  CAS  Google Scholar 

  19. Takemura G, Onodera T, Millard RW, Ashraf M: Demonstration of hydroxyl radical and its role in hydrogen peroxide-induced myocardial injury: hydroxyl radical dependent and independent mechanisms. Free Radic Biol Med 15: 13–25, 1993

    Article  PubMed  CAS  Google Scholar 

  20. Kaul N, Siveski-Iliskovic N, Hill M, Slezak J, Singal PK: Free radicals and the heart. J Pharmacol Toxicol Methods 30: 55–67, 1993

    Article  PubMed  CAS  Google Scholar 

  21. Pagliaro P, Mancardi D, Rastaldo R, Penna C, Gattullo D, Miranda KM, Feelisch M, Wink DA, Paolocci N: Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning. Free Radic Biol Med 34: 33–43, 2003

    Article  PubMed  CAS  Google Scholar 

  22. Baker JE, Boerboom LE, Olinger GN: Age-related changes in the ability of hypothermia and cardioplegia to protect ischemic rabbit myocardium. J Thorac Cardiovasc Surg 96: 717–724, 1988

    PubMed  CAS  Google Scholar 

  23. Maupoil V, Rochette L: Evalulation of free radical and lipid peroxide formation during global ischemia and reperfusion in isolated perfused rat heart. Cardiovasc Drugs Ther 2: 615–621, 1988

    Article  PubMed  CAS  Google Scholar 

  24. Ambrosio G, Zweier JL, Duilio C, Kuppusamy P, Santoro G, Elia PP, Tritto I, Cirillo P, Condorelli M, Chiariello M: Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow. J Biol Chem 268: 18532–18541, 1993

    PubMed  CAS  Google Scholar 

  25. Venditti P, Masullo P, Di Meo S: Effects of myocardial ischemia and reperfusion on mitochondrial function and susceptibility to oxidative stress. Cell Mol Life Sci 58: 1528–1537, 2001

    Article  PubMed  CAS  Google Scholar 

  26. Kaneko M, Beamish RE, Dhalla NS: Reduction of calcium channel antagonist binding sites by oxygen free radicals in rat heart. J Mol Cell Cardiol 21: 935–943, 1989

    Article  PubMed  CAS  Google Scholar 

  27. Leedle RA, Aust SD: The effect of glutathione on the vitamin E requirement for inhibition of liver microsomal lipid peroxidation. Lipids 25: 241–245, 1990

    PubMed  CAS  Google Scholar 

  28. Murry CE, Richard VJ, Reimer KA, Jennings RB: Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during a sustained ischemic episode. Circ Res 66: 913–931, 1990

    PubMed  CAS  Google Scholar 

  29. Otani H, Tanaka H, Inoue T, Umemoto M, Omoto K, Tanaka K, Sato T, Osako T, Masuda A, Nonoyama A et al.: (1984). In vitro study on contribution of oxidative metabolism of isolated rabbit heart mitochondria to myocardial reperfusion injury. Circ Res 55: 168–175, 1984

    PubMed  CAS  Google Scholar 

  30. Ambrosio G., Zweier JL, Flaherty JT: The relationship between oxygen radical generation and impairment of myocardial energy metabolism following post-ischemic reperfusion. J Mol Cell Cardiol 23: 1359–74, 1991

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Biochemistry, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China

    Ying Du & Kam Ming Ko

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  1. Ying Du
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  2. Kam Ming Ko
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Correspondence to Kam Ming Ko.

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Du, Y., Ko, K.M. Effects of pharmacological preconditioning by emodin/oleanolic acid treatment and/or ischemic preconditioning on mitochondrial antioxidant components as well as the susceptibility to ischemia-reperfusion injury in rat hearts. Mol Cell Biochem 288, 135–142 (2006). https://doi.org/10.1007/s11010-006-9129-3

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  • DOI: https://doi.org/10.1007/s11010-006-9129-3

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