Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Korean Red Ginseng enhances cardiac hemodynamics on doxorubicin-induced toxicity in rats

  • Jang, Young-Jin (College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University) ;
  • Lee, Dongbin (College of Veterinary Medicine, Gyeongsang National University) ;
  • Hossain, Mohammad Amjad (College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University) ;
  • Aravinthan, Adithan (College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University) ;
  • Kang, Chang-Won (College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University) ;
  • Kim, Nam Soo (College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University) ;
  • Kim, Jong-Hoon (College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University)
  • Received : 2018.08.28
  • Accepted : 2019.03.08
  • Published : 2020.05.15
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Korean Red Ginseng (KRG) has been known to possess many ginsenosides. These ginsenosides are used for curing cardiovascular problems. The present study show the protective potential of KRG against doxorubicin (DOX)-induced myocardial dysfunction, by assessing electrocardiographic, hemodynamic, and biochemical parameters and histopathological findings. Methods: Animals were fed a standard chow and adjusted to their environment for 3 days before the experiments. Next, the rats were equally divided into five groups (n = 9, each group). The animals were administered with KRG (250 and 500 mg/kg) for 10 days and injected with DOX (20 mg/kg, subcutaneously, twice at a 24-h interval) on the 8th and 9th day. Electrocardiography and echocardiography were performed to study hemodynamics. Plasma levels of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde were measured. In addition, the dose of troponin I and activity of myeloperoxidase in serum and cardiac tissue were analyzed, and the histopathological findings were evaluated using light microscopy. Results: Administration of KRG at a dose of 250 and 500 mg/kg recovered electrocardiographic changes, ejection fraction, fractional shortening, left ventricular systolic pressure, the maximal rate of change in left ventricle contraction (-dP/dtmax), and left ventricle relaxation (-dP/dtmax). In addition, KRG treatment significantly normalized the oxidative stress markers in plasma, dose dependently. In addition, the values of troponin I and myeloperoxidase were ameliorated by KRG treatment, dose dependently. And, KRG treatment showed better histopathological findings when compared with the DOX control group. Conclusion: These mean that KRG mitigates myocardial damage by modulating the hemodynamics, histopathological abnormality, and oxidative stress related to DOX-induced cardiomyopathy in rats. The results of the present study show protective effects of KRG on cardiac toxicity.

Keywords

References

  1. Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 2004;56:185-229. https://doi.org/10.1124/pr.56.2.6
  2. Bast A, Haenen GR, Bruynzeel AM, Vander Vijgh WJ. Protection by flavonoids against anthracycline cardiotoxicity: from chemistry to clinical trials. Cardiovasc Toxicol 2007;7:154-9. https://doi.org/10.1007/s12012-007-0018-0
  3. Saeki K, Obi I, Ogiku N, Shigekawa M, Imagawa T, Matsumoto T. Doxorubicin directly binds to the cardiac-type ryanodine receptor. Life Sci 1998;19:450-7.
  4. Olson RD, Mushlin PS. Doxorubicin cardiotoxicity analysis of prevailing hypotheses. FASEB J 1990;4:3076-86. https://doi.org/10.1096/fasebj.4.13.2210154
  5. Akimoto H, Bruno NA, Slate DL, Billingham ME, Torti SV, Torti FM. Effect of verapamil on doxorubicin cardiotoxicity: altered muscle gene expression in cultured neonatal rat cardiomyocytes. Cancer Res 1993;53:4658-64.
  6. Singal PK, Iliskovic N, Li T, Kumar D. Adriamycin cardiomyopathy: pathophysiology and prevention. FASEB J 1997;11:931-6. https://doi.org/10.1096/fasebj.11.12.9337145
  7. Singal PK, Deally CM, Weinberg LE. Subcellular effects of adriamycin in the heart: a concise review. J Mol Cell Cardiol 1987;19:817-28. https://doi.org/10.1016/S0022-2828(87)80392-9
  8. Noiri E, Nagano N, Negishi K, Doi K, Miyata S, Abe M, Tanaka T, Okamoto K, Hanafusa N, Kondo Y, et al. Efficacy of darbepoetin in doxorubicin-induced cardiorenal injury in rats. Nephron Exp Nephrol 2006;104:e6-14. https://doi.org/10.1159/000093258
  9. Arbel Y, Swartzon M, Justo D. QT prolongation and Torsades de Pointes in patients previously treated with anthracyclines. Anti Drugs 2007;18:493-8. https://doi.org/10.1097/CAD.0b013e328012d023
  10. Singal PK, Iliskovic N. Doxorubicin induced cardiomyopathy. N Engl J Med 1998;339:900-5. https://doi.org/10.1056/NEJM199809243391307
  11. Park JD. Recent studies on the chemical constituents of Korean ginseng (Panax ginseng C. A. Meyer). Korean J Ginseng Sci 1996;20:389-415.
  12. Lee H, Kim J, Lee SY, Park JH, Hwang GS. Processed Panax ginseng, sun ginseng, decreases oxidative damage induced by tert-butyl hydroperoxide via regulation of antioxidant enzyme and anti-apoptotic molecules in HepG2 cells. J Ginseng Res 2012;36:248-55. https://doi.org/10.5142/jgr.2012.36.3.248
  13. Lim KH, Cho JY, Kim B, Bae BS, Kim JH. Red ginseng (Panax ginseng) decreases isoproterenol-induced cardiac injury via antioxidant properties in porcine. J Med Food 2014;17(1):111-8. https://doi.org/10.1089/jmf.2013.2768
  14. Kwon SW, Han SB, Park IH, Kim JM, Park MK, Park JH. Liquid chromatographic determination of less polar ginsenosides in processed ginseng. J Chromatogr A 2001;921:335-9. https://doi.org/10.1016/S0021-9673(01)00869-X
  15. Al-Harthi SE, Alarabi OM, Ramadan WS, Alaama MN, Al-Kreathy HM, Damanhouri ZA, Khan LM, Osman AM. Amelioration of doxorubicin-induced cardiotoxicity by resveratrol. Mol Med Rep 2014;10(3):1455-60. https://doi.org/10.3892/mmr.2014.2384
  16. Berthiaume JM, Oliveira PJ, Fariss MW, Wallace KB. Dietary vitamin E decreases doxorubicin-induced oxidative stress without preventing mitochondrial dysfunction. Cardiovasc Toxicol 2005;5(3):257-67. https://doi.org/10.1385/CT:5:3:257
  17. Zhang XJ, Cao XQ, Zhang CS, Zhao Z. $17{\beta}$-estradiol protects against doxorubicin-induced cardiotoxicity in male Sprague-Dawley rats by regulating NADPH oxidase and apoptosis genes. Mol Med Rep 2017;15(5):2695-702. https://doi.org/10.3892/mmr.2017.6332
  18. Yeung PK, Purcell C, Akhoundi F, Agu RU. Adenosine and adenosine 5'-triphosphate catabolism in systemic blood as a potential biomarker for doxorubicin cardiotoxicity in an experimental rat model in vivo. Cardiovasc Hematol Disord Drug Targets 2018. https://doi.org/10.2174/1871529X18666180406125225.
  19. Xin YF, Zhou GL, Deng ZY, Chen YX, Wu YG, Xu PS, Xuan YX. Protective effect of Lycium barbarum on doxorubicin-induced cardiotoxicity. Phytother Res 2007;21:1020-4. https://doi.org/10.1002/ptr.2186
  20. Farraj AK, Hazari MS, Cascio WE. The utility of the small rodent electrocardiogram in toxicity. Toxicol Sci 2011;121:11-30. https://doi.org/10.1093/toxsci/kfr021
  21. Ammar ESM, Said SA, El-Damarawy SL, Suddek GM. Cardioprotective effect of grape seed proanthocyanidins on doxorubicin-induced cardiac toxicity in rats. Pharmaceut Biol 2013;51:339-44. https://doi.org/10.3109/13880209.2012.729065
  22. Sabatini CF, O'Sullivan ML, Valcour JE, Sears W, Johnson RJ. Effects of injectable anesthetic combinations on left ventricular function and cardiac morphology in Sprague-Dawley rats. J Am Assoc Lab Anim Sci 2013;52(1):34-43.
  23. Farshid AA, Tamaddonfard E, Simaee N, Mansouri S, Najafi S, Asri-Rezaee S, Alavi H. Effects of histidine and N-acetylcysteine on doxorubicin-induced cardiomyopathy in rats. Cardiovasc Toxicol 2014;14(2):153-61. https://doi.org/10.1007/s12012-013-9239-6
  24. Mishra HP, Fridovich I. The role of superoxide anion in the autooxidation of epinephrine and a simple assay of superoxide dismutase. J Biol Chem 1972;247:3170-5. https://doi.org/10.1016/S0021-9258(19)45228-9
  25. Aebi H. Catalase in vivo. Meth Enzymol 1984;105:121-6. https://doi.org/10.1016/S0076-6879(84)05016-3
  26. Rotruck JT, Pope AL, Ganther HE. Selenium; biochemical role as a component of glutathione peroxidase. Science 1979;179:588-90. https://doi.org/10.1126/science.179.4073.588
  27. Rathore N, John S, Kale M, Bhatnagar D. Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat tissues. Pharmacol Res 1998;38:297-303. https://doi.org/10.1006/phrs.1998.0365
  28. O'Brien PJ, Smith DE, Knechtel TJ, Marchak MA, Pruimboom-Brees I, Brees DJ, Spratt DP, Archer FJ, Butler P, Potter AN, et al. Cardiac troponin I is a sensitive, specific biomarker of cardiac injury in laboratory animals. Lab Anim 2006;40:153-71. https://doi.org/10.1258/002367706776319042
  29. Ikizler M, Erkasap N, Dernek S, Kural T, Kaygisiz Z. Dietary polyphenol quercetin protects rat hearts during reperfusion: enhanced antioxidant capacity with chronic treatment. Anadolu Kardiyol Derg 2007;7:404-10.
  30. Mullane KM, Kraemer R, Smith B. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J Pharmacol Med 1985;14:157-67.
  31. Cigremis Y, Parlakpinar H, Polat A, Colak C, Ozturk F, Sahna E, Ermis N, Acet A. Beneficial role of aminoguanidine on acute cardiomyopathy related to doxorubucine treatment. Mol Cell Biochem 2006;85:149-54.
  32. Lim KH, Ko D, Kim JH. Cardioprotective potential of Korean Red Ginseng extract on isoproterenol-induced cardiac injury in rats. J Ginseng Res 2013;37(3):273-82. https://doi.org/10.5142/jgr.2013.37.273
  33. Klawitter PF, Murray HN, Clanton TL, Angelos MG. Reactive oxygen species generated during myocardial ischemia enable energetic recovery during reperfusion. Am J Physiol Heart Circ Physiol 2002;283:H1656-61. https://doi.org/10.1152/ajpheart.00041.2002
  34. Kim JH. Protective roles of ginseng saponin in cardiac ischemia and reperfusion injury. J Ginseng Res 2009;33:283-93. https://doi.org/10.5142/JGR.2009.33.4.283
  35. Aravinthan A, Kim JH, Antonisamy P, Kang CW, Choi J, Kim NS, Kim JH. Ginseng total saponin attenuates myocardial injury via anti-oxidative and anti-inflammatory properties. J Ginseng Res 2015;39(3):206-12. https://doi.org/10.1016/j.jgr.2014.12.001
  36. Arhan E, Aycicek S, Akaln N, Guven A, Kose G. Cardiac effects of carbamazepine treatment in childhood epilepsy. Neurologist 2009;15(5):268-73. https://doi.org/10.1097/NRL.0b013e31818600a4
  37. Kaul N, Siveski-Iliskovic N, Hill M, Slezak J, Singal PK. Free radicals and the heart. J Pharmacol Toxicol Methods 1993;30:55-67. https://doi.org/10.1016/1056-8719(93)90008-3
  38. Robicsek F, Schaper J. Reperfusion injury: fact or myth? J Card Surg 1997;12:133-7. https://doi.org/10.1111/j.1540-8191.1997.tb00112.x
  39. Lim KH, Kang CW, Choi JY, Kim JH. Korean red ginseng induced cardioprotection against myocardial ischemia in Guinea pig. Korean J Physiol Pharmacol 2013;17(4):283-9. https://doi.org/10.4196/kjpp.2013.17.4.283

Cited by

  1. Trehalose alleviates doxorubicin‐induced cardiotoxicity in female Swiss albino mice by suppression of oxidative stress and autophagy vol.35, pp.9, 2020, https://doi.org/10.1002/jbt.22859