The effect of hydroalcoholic extract of Cydonia oblonga Miller leaf on doxorubicin-induced cardiac injury in rat

Document Type: Research Paper

Authors

1 Department of Cardiology, Faculty of Medicine, Shahed University, Tehran, Iran

2 Neurophysiology Research Center, Shahed University, Tehran, Iran

3 Medical Students research committee, Shahed University, Tehran, Iran

Abstract

Background and Objective: Doxorubicin is one of the most common drugs for chemotherapy. The complications of doxorubicin are cardiac toxicity due to oxidative stress. Cydonia oblonga Miller leaf (COL) contains flavonoids and phenolic antioxidants. Due to the presence of antioxidant compounds in COL, the aim of this study was to evaluate the effect of hydroalcoholic extract of COL on doxorubicin-induced cardiac injury in rat.
Materials and Methods: In this experimental investigation, 32 male Wistar rats were divided into 4 groups: control, control under treatment of hydroalcoholic extract of COL, doxorubicin and doxorubicin under treatment of hydroalcoholic extract of COL. In treatment groups, 200 mg/kg of hydroalcoholic extract of COL was injected intraperitoneally one hour after the first dose of doxorubicin for 2 weeks and administered daily. For induction of cardiac toxicity, doxorubicin was injected at a dose of 15 mg/kg intraperitoneally. After two weeks of treatment, the rats were anesthetized with diethyl ether and their heart was removed. After tissue homogenate was prepared, oxidative stress markers were measured using specific kits.
Results: The results of this study demonstrated that doxorubicin increases malondialdehyde and reduced glutathione and catalase activity in the cardiac tissue of rats. Two weeks of treatment with hydroalcoholic extract of COL significantly reduced the malondialdehyde level and increased glutathione. The increase in catalase activity was not statistically significant.
Conclusion: According to the results of this study, COL with phenolic and flavonoid compounds and antioxidant activity seems to attenuate lipid peroxidation and oxidative stress in doxorubicin induced cardiac toxicity.

Keywords


  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA: A Cancer Journal for Clinicians 2015; 65(1):5–29.
  2. Li M, Xiong ZG. Ion channels as targets for cancer therapy. International Journal of Physiology, Pathophysiology and Pharmacology 2011; 3(2):156–66.
  3. Zanetti SR, Maldonado EN, Aveldano MI. Doxorubicin Affects Testicular Lipids with Long- Chain(C18-C22) and VeryLong- Chain(C24-C32) Polyunsaturated Fatty Acids. Cancer Research 2007; 67: (14).
  4. Baumgartner A, Schmid TE, Cemeli E, Anderson D. Parallel evaluation of doxorubicin-induced genetic damage in human lymphocytes and sperm using the comet assay and spectral karyotyping. Mutagenesis 2004; 19(4):313-8.
  5. Ichihara S, Yamada Y, Kawai Y, Osawa T, Furuhashi K, Duan Z, et al. Roles of oxidative stress and Akt signaling in doxorubicin cardiotoxicity. Biochemical and Biophysical Research Communications 2007; 359(1):27-33.
  6. Asmis R, Qiao M, Rossi RR, Cholewa J, Xu L, Asmis LM. Adriamycin promotes macrophage dysfunction in mice. Free Radical Biology and Medicine 2006; 41(1):165-74.
  7. Brown SA, Sandhu N, Herrmann J. System’s biology approaches to adverse drug effects: the example of cardio-oncology. Nature Reviews Clinical Oncology 2015;12(12):718-31.
  8. Chung WB, Youn HJ. Pathophysiology and preventive strategies of anthracycline-induced cardiotoxicity. The Korean Journal of Internal Medicine 2016; 31(4):625-633.
  9. Ojha S, Al Taee H, Goyal S, Mahajan UB, Patil CR, Arya DS, et al. Cardioprotective Potentials of Plant-Derived Small Molecules against Doxorubicin Associated Cardiotoxicity. Oxidative Medicine and Cellular Longevity 2016; 2016:5724973.
  10. Angsutararux P, Luanpitpong S, Issaragrisil S. Chemotherapy-Induced Cardiotoxicity: Overview of the Roles of Oxidative Stress. Oxidative Medicine and Cellular Longevity 2015; 795602.
  11. Ashrafi J, Dabidi Roshan V, Zolfagharzadeh F. Tissue Toxicity Induced by Doxorubicin in Rats: Protective Role of Aerobic Regular Exercise. The Journal of Urmia University of Medical Sciences 2014; 25 (4) :353-362
  12. Carvalho C, Santos RX, Cardoso S, Correia S, Oliveira PJ, Santos MS, et al. Doxorubicin: The Good, the Bad and the Ugly Effect. Current Medicinal Chemistry 2009; 16(25):3267-85.
  13. Ashrafi J, Dabidi Roshan V, Mahjoub S. Cardioprotective effects of aerobic regular exercise against doxorubicin-induced oxidative stress in rat. African Journal of Pharmacy and Pharmacology 2012; 6(31): 2380-8.
  14. Chicco AJ, Hydock DS, Schneider CM, Hayward R. Low-intensity exercise training during doxorubicin treatment protects against cardiotoxicity. Journal of Applied Physiology 2006; 100: 519–27.
  15. Ascensao A, Magalhaes J, Soares J, Ferreira R, Neuparth M, Marques F, et al. Endurance training attenuates doxorubicin-induced cardiac oxidative damage in mice. International Journal of Cardiology 2005; 100: 451–60.
  16. Dziegiel P, Surowiak P, Zabel M. Correlation of histopathological and biochemical appraisal of anthracyclin-induced myocardium damage. Folia Histochemica et Cytobiologica 2002; 40: 127–8.
  17. Yen HC, OberleyTD, Vichitbandha S, Ho YS, Clair DK. The protective role of manganese superoxide dismutase against adriamycin-induced acute cardiac toxicity in transgenic mice. Journal of Clinical Investigation 1996; 98: 1253–60.
  18. Ascensao A, Magalhaes J, Soares JM, Ferreira R, Neuparth MJ, Marques F, et al. Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis. American Journal of Physiology-Heart and Circulatory Physiology 2005; 289(2): H722–31.
  19. Kavazis AN, Smuder AJ, Min K, Tümer N, Powers SK. Short-term exercise training protects against doxorubicin-induced cardiac mitochondrial damage independent of HSP72. American Journal of Physiology-Heart and Circulatory Physiology 2010; 299(5):H1515-24.
  20. Aliasl F, Toliyat T, Mohammadi A, Minaee B, Samadi N, Aliasl J, et al. Medicinal Properties of Cydonia Oblonga Mill Fruit (Pulp and Peel) in Iranian Traditional Medicine and Modern Phototherapy. Traditional Integrative Medicine 2016; 1(3): 122-8.
  21. Hajizadeh Moghaddam A, Kianmehr A. The Protective Effect of Quince (Cydonia oblonga Miller) Leaf Extract on Locomotor Activity and Anxiety-Like Behaviors in a Ketamine Model of Schizophrenia. Journal of Arak University of Medical Sciences 2016; 19(5):31-41
  22. Oliveira AP, Pereira JA, Andrade PB, Valentão P, Seabra RM, Silva BM. Phenolic profile of Cydonia oblonga Miller leaves. Journal of Agricultural and Food Chemistry 2007; 55(19):7926-30.
  23. Khoubnasabjafari M, Jouyban A. A review of phytochemistry and bioactivity of quince (Cydonia oblonga Mill.). Journal of Medicinal Plants Research 2011; 5(16):3577-94.
  24. Khademi F, Danesh B, Mohammad Nejad D, Soleimani Rad J. The comparative effects of atorvastatin and quince leaf extract on atherosclerosis. Iranian Red Crescent Medicinal Journal 2013;15(8):639-43
  25. Carvalho M, Silva BM, Silva R, Valentão P, Andrade PB, Bastos ML. First report on Cydonia oblonga Miller anticancer potential: differential antiproliferative effect against human kidney and colon cancer cells. Journal of Agricultural and Food Chemistry 2010; 58(6): 3366-70
  26. Marques V, Farah A. Chlorogenic acids and related compounds in medicinal plants and infusions. Food Chemistry 2009; 113(4):1370- 6.
  27. Ansari I, Yaghoutpoor E, Kiasalari Z, Khalili M. Methadone and haloperidol combination effect on the acquisition and expression of morphine tolerance and dependence in male mice. Journal of Basic and Clinical Pathophysiology 2013; 1(2): 15-22.
  28. Ansari I, Vahidi S, Khalili M. Methadone and valproate combination effect on acquisition and expression of morphine dependence and tolerance in male mice. Journal of Basic and Clinical Pathophysiology 2013; 2(1): 15-22.
  29. Umar A, Iskandar G, Aikemu A, Yiming W, Zhou W, Berké B, et al. Effects of Cydonia oblonga Miller leaf and fruit flavonoids on blood lipids and anti-oxydant potential in hyperlipidemia rats. Journal of Ethnopharmacology 2015; 169:239-43.
  30. Gholami S, Hosseini MJ, Jafari L, Omidvar F, Kamalinejad M, Mashayekhi V, et al. Mitochondria as a Target for the Cardioprotective Effects of Cydonia oblonga Mill. and Ficus carica L. in Doxorubicin-Induced Cardiotoxicity. Drug Research 2017; 67: 358–365
  31. Ghosian Moghadam MH, Ansari I, Roghani M, Ghanem A, Mehdizade N. The Effect of Oral Administration of Hypericum Perforatum on Serum Glucose and Lipids, Hepatic Enzymes and Lipid Peroxidation in Streptozotocin-Induced Diabetic Rats. Galen Medical Journal 2017; 6(4):319-329.
  32. Ghosian Moghaddam M, Ansari I, Roghani M, Moradi M. The Effects of Origanum Majorana on Oxidative Stress and Histopathology of Renal Tissue among Streptozotocin-Induced Diabetic Rats. Thrita 2013; 2(3):29-34.
  33. Baluchnejadmojarad T, Zeinali H, Roghani M. Scutellarin alleviates lipopolysaccharide-induced cognitive deficits in the rat: Insights into underlying mechanisms. International Immunopharmacology 2018; 54:311-319.
  34. Sayed AEH, Ismail RFK. Endocrine disruption, oxidative stress, and testicular damage induced by 4-nonylphenol in Clarias gariepinus: the protective role of Cydonia oblonga. Fish Physiology and Biochemistry 2017; 43(4):1095-1104.
  35. Abliz A, Aji Q, Abdusalam E, Sun X, Abdurahman A, Zhou W, et al. Effect of Cydonia oblonga Mill. leaf extract on serum lipids and liver function in a rat model of hyperlipidaemia. Journal of Ethnopharmacology 2014; 151(2):970-4.
  36. Zhou W, Abdusalam E, Abliz P, Reyim N, Tian S, Aji Q, et al. Effect of Cydonia oblonga Mill. fruit and leaf extracts on blood pressure and blood rheology in renal hypertensive rats. Journal of Ethnopharmacology 2014;152(3):464-9