Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Cytoprotective effect of rhamnetin on miconazole-induced H9c2 cell damage

  • Lee, Kang Pa (Department of Medical Science, School of Medicine) ;
  • Kim, Jai-Eun (Department of Pathology, College of Korean Medicine, Dongguk University) ;
  • Park, Won-Hwan (Department of Diagnosis, College of Korean Medicine, Dongguk University)
  • Received : 2015.04.22
  • Accepted : 2015.06.29
  • Published : 2015.12.01
Download PDF
⟨ Previous Next ⟩

Abstract

BACKGROUND/OBJECTIVES: Reactive oxygen species (ROS) formation is closely related to miconazole-induced heart dysfunction. Although rhamnetin has antioxidant effects, it remained unknown whether it can protect against miconazole-induced cardiomyocyte apoptosis. Thus, we investigated the effects of rhamnetin on miconazole-stimulated H9c2 cell apoptosis. MATERIALS/METHODS: Cell morphology was observed by inverted microscope and cell viability was determined using a WelCount$^{TM}$ cell proliferation assay kit. Miconazole-induced ROS production was evaluated by fluorescence-activated cell sorting with 6-carboxy-2',7'-dichlorofluoroscein diacetate ($H_2DCF$-DA) stain. Immunoblot analysis was used to determine apurinic/apyrimidinic endonuclease 1 (APE/Ref-1) and cleaved cysteine-aspartic protease (caspase) 3 expression. NADPH oxidase levels were measured using real-time polymerase chain reaction. RESULTS: Miconazole (3 and $10{\mu}M$) induced abnormal morphological changes and cell death in H9c2 cells. Rhamnetin enhanced the viability of miconazole ($3{\mu}M$)-treated cells in a dose-dependent manner. Rhamnetin (1 and $3{\mu}M$) treatment downregulated cleaved caspase 3 and upregulated APE/Ref-1 expression in miconazole-stimulated cells. Additionally, rhamnetin significantly reduced ROS generation. CONCLUSIONS: Our data suggest that rhamnetin may have cytoprotective effects in miconazole-stimulated H9c2 cardiomyocytes via ROS inhibition. This effect most likely occurs through the upregulation of APE/Ref-1 and attenuation of hydrogen peroxide levels.

Keywords

References

  1. Mendis S, Lindholm LH, Anderson SG, Alwan A, Koju R, Onwubere BJ, Kayani AM, Abeysinghe N, Duneas A, Tabagari S, Fan W, Sarraf-Zadegan N, Nordet P, Whitworth J, Heagerty A. Total cardiovascular risk approach to improve efficiency of cardiovascular prevention in resource constrain settings. J Clin Epidemiol 2011;64:1451-62. https://doi.org/10.1016/j.jclinepi.2011.02.001
  2. Ministry of Health and Welfare, Korea Centers for Disease Control and Prevention. Korea Health Statistics 2012: Korea National Health and Nutrition Examination Survey (KNHANES V-3). Cheongwon: Korea Centers for Disease Control and Prevention; 2013.
  3. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362:801-9. https://doi.org/10.1038/362801a0
  4. Müller C. New ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Swiss Med Wkly 2012;142:w13514.
  5. Zweier JL, Talukder MA. The role of oxidants and free radicals in reperfusion injury. Cardiovasc Res 2006;70:181-90. https://doi.org/10.1016/j.cardiores.2006.02.025
  6. Coley KC, Crain JL. Miconazole-induced fatal dysrhythmia. Pharmacotherapy 1997;17:379-82.
  7. Kobayashi D, Kondo K, Uehara N, Otokozawa S, Tsuji N, Yagihashi A, Watanabe N. Endogenous reactive oxygen species is an important mediator of miconazole antifungal effect. Antimicrob Agents Chemother 2002;46:3113-7. https://doi.org/10.1128/AAC.46.10.3113-3117.2002
  8. Irani K, Xia Y, Zweier JL, Sollott SJ, Der CJ, Fearon ER, Sundaresan M, Finkel T, Goldschmidt-Clermont PJ. Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science 1997;275:1649-52. https://doi.org/10.1126/science.275.5306.1649
  9. Dumaine R, Roy ML, Brown AM. Blockade of HERG and Kv1.5 by ketoconazole. J Pharmacol Exp Ther 1998;286:727-35.
  10. Lee Y, Gustafsson AB. Role of apoptosis in cardiovascular disease. Apoptosis 2009;14:536-48. https://doi.org/10.1007/s10495-008-0302-x
  11. Pulkki KJ. Cytokines and cardiomyocyte death. Ann Med 1997;29:339-43. https://doi.org/10.3109/07853899708999358
  12. Shih PH, Yeh CT, Yen GC. Anthocyanins induce the activation of phase II enzymes through the antioxidant response element pathway against oxidative stress-induced apoptosis. J Agric Food Chem 2007;55:9427-35. https://doi.org/10.1021/jf071933i
  13. Kim DE, Kim B, Shin HS, Kwon HJ, Park ES. The protective effect of hispidin against hydrogen peroxide-induced apoptosis in H9c2 cardiomyoblast cells through Akt/GSK-$3{\beta}$ and ERK1/2 signaling pathway. Exp Cell Res 2014;327:264-75. https://doi.org/10.1016/j.yexcr.2014.07.037
  14. Baines CP, Molkentin JD. STRESS signaling pathways that modulate cardiac myocyte apoptosis. J Mol Cell Cardiol 2005;38:47-62. https://doi.org/10.1016/j.yjmcc.2004.11.004
  15. Glasauer A, Chandel NS. Targeting antioxidants for cancer therapy. Biochem Pharmacol 2014;92:90-101.
  16. Nunez-Cordoba JM, Martinez-Gonzalez MA. Antioxidant vitamins and cardiovascular disease. Curr Top Med Chem 2011;11:1861-9. https://doi.org/10.2174/156802611796235143
  17. Won KJ, Lin HY, Jung S, Cho SM, Shin HC, Bae YM, Lee SH, Kim HJ, Jeon BH, Kim B. Antifungal miconazole induces cardiotoxicity via inhibition of APE/Ref-1-related pathway in rat neonatal cardiomyocytes. Toxicol Sci 2012;126:298-305. https://doi.org/10.1093/toxsci/kfr347
  18. Ozipek M, Calis I, Ertan M, Ruedi P. Rhamnetin 3-p-coumaroylrhamninoside from Rhamnus petiolaris. Phytochemistry 1994;37:249-53. https://doi.org/10.1016/0031-9422(94)85035-6
  19. Igarashi K, Ohmuma M. Effects of isorhamnetin, rhamnetin, and quercetin on the concentrations of cholesterol and lipoperoxide in the serum and liver and on the blood and liver antioxidative enzyme activities of rats. Biosci Biotechnol Biochem 1995;59:595-601. https://doi.org/10.1271/bbb.59.595
  20. Yamamoto N, Moon JH, Tsushida T, Nagao A, Terao J. Inhibitory effect of quercetin metabolites and their related derivatives on copper ion-induced lipid peroxidation in human low-density lipoprotein. Arch Biochem Biophys 1999;372:347-54. https://doi.org/10.1006/abbi.1999.1516
  21. Slimen IB, Najar T, Ghram A, Dabbebi H, Ben Mrad M, Abdrabbah M. Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review. Int J Hyperthermia 2014;30:513-23. https://doi.org/10.3109/02656736.2014.971446
  22. Sullivan LB, Chandel NS. Mitochondrial reactive oxygen species and cancer. Cancer Metab 2014;2:17. https://doi.org/10.1186/2049-3002-2-17
  23. Paneni F, Costantino S, Cosentino F. Role of oxidative stress in endothelial insulin resistance. World J Diabetes 2015;6:326-32. https://doi.org/10.4239/wjd.v6.i2.326
  24. Brown DI, Griendling KK. Regulation of signal transduction by reactive oxygen species in the cardiovascular system. Circ Res 2015;116:531-49. https://doi.org/10.1161/CIRCRESAHA.116.303584
  25. Manea A. NADPH oxidase-derived reactive oxygen species: involvement in vascular physiology and pathology. Cell Tissue Res 2010; 342:325-39. https://doi.org/10.1007/s00441-010-1060-y
  26. Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007;87:245-313. https://doi.org/10.1152/physrev.00044.2005
  27. Puca R, Nardinocchi L, Starace G, Rechavi G, Sacchi A, Givol D, D'Orazi G. Nox1 is involved in p53 deacetylation and suppression of its transcriptional activity and apoptosis. Free Radic Biol Med 2010;48:1338-46. https://doi.org/10.1016/j.freeradbiomed.2010.02.015
  28. Kuroda J, Ago T, Matsushima S, Zhai P, Schneider MD, Sadoshima J. NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc Natl Acad Sci U S A 2010;107:15565-70. https://doi.org/10.1073/pnas.1002178107
  29. Kuroda J, Sadoshima J. NADPH oxidase and cardiac failure. J Cardiovasc Transl Res 2010;3:314-20. https://doi.org/10.1007/s12265-010-9184-8
  30. Matsuno K, Iwata K, Matsumoto M, Katsuyama M, Cui W, Murata A, Nakamura H, Ibi M, Ikami K, Zhang J, Matoba S, Jin D, Takai S, Matsubara H, Matsuda N, Yabe-Nishimura C. NOX1/NADPH oxidase is involved in endotoxin-induced cardiomyocyte apoptosis. Free Radic Biol Med 2012;53:1718-28. https://doi.org/10.1016/j.freeradbiomed.2012.08.590
  31. Park ES, Kang JC, Jang YC, Park JS, Jang SY, Kim DE, Kim B, Shin HS. Cardioprotective effects of rhamnetin in H9c2 cardiomyoblast cells under $H_2O_2$-induced apoptosis. J Ethnopharmacol 2014;153:552-60. https://doi.org/10.1016/j.jep.2014.02.019
  32. Thakur S, Sarkar B, Cholia RP, Gautam N, Dhiman M, Mantha AK. APE1/Ref-1 as an emerging therapeutic target for various human diseases: phytochemical modulation of its functions. Exp Mol Med 2014;46:e106. https://doi.org/10.1038/emm.2014.42

Cited by

  1. Maternal Exposure to PM2.5 during Pregnancy Induces Impaired Development of Cerebral Cortex in Mice Offspring vol.19, pp.1, 2018, https://doi.org/10.3390/ijms19010257
  2. L.) in lipopolysaccharide-stimulated BV2 cells and ICR mice vol.12, pp.1, 2018, https://doi.org/10.4162/nrp.2018.12.1.13
  3. The Active Compounds of Yixin Ningshen Tablet and Their Potential Action Mechanism in Treating Coronary Heart Disease- A Network Pharmacology and Proteomics Approach vol.2020, pp.None, 2015, https://doi.org/10.1155/2020/4912395
  4. Modulations of Cardiac Functions and Pathogenesis by Reactive Oxygen Species and Natural Antioxidants vol.10, pp.5, 2015, https://doi.org/10.3390/antiox10050760