Naringin Effectively Protects Cardiomyocytes Against Hypoxia/Reoxygenation Injury
Main Article Content
Abstract
This study was conducted to evaluate the protective effect of Naringin (NAR) on H9C2 cardiomyocytes in hypoxia/reoxygenation (HR) injury in vitro induced by the hypoxia chamber. Methods: H9C2 cells were grown under normal (control) and HR conditions. The viability, cardiolipin content and mitochondrial membrane potential of H9C2 cells in experimental groups were analyzed by using suitable kits. Results: The obtained results showed that the addition of Naringin (16÷160 µM) significantly increased the survival rate of H9C2 cells under HR conditions. In particular, NAR had the highest efficiency in preserving mitochondrial function at concentrations of 80 µM and 160 µM. In HR-exposed H9C2 cell group, the cardiolipin content and mitochondrial membrane potential values of H9C2 cells were decreased sharply with that of control (71,64±1,37% and 68,12±2,78%, p<0,05). Interestingly, mitochondrial cardiolipin contents were signigicantly increased in H9C2 cells post-hypoxic treated wtih NAR at dose of 80 µM 160 µM to 87,76±1,89% and 81,09±1,21%. Additionally, post-hypoxic supplementation of NAR at concentration of 80 µM and 160 µM effectively increased mitochondrial membrane potential values. Conclusion: The obtained results are preliminary data on the effects of NAR in protecting mitochondrial-targeted cardiomyocytes against HR injury.
Keywords:
H9C2, Cardiolipin, Mitochondrial membrane potential.
References
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[3] M. Andrew, M. A. George, S. Paul, Mitochondria as a Drug Target in Ischemic Heart Disease and Cardiomyopathy, Circulation Research,Vol. 111,
No. 9, 2012, pp. 1222-1236, https://doi.org/10.1161/CIRCRESAHA.112.265660.
[4] M. A. Alam et al., Effect of Citrus Flavonoids, Naringin and Naringenin, on Metabolic Syndrome and Their Mechanisms of Action, Advances in Nutrition (Bethesda, Md.), Vol. 5, No. 4, 2014, pp. 404-417, https://doi.org/10.3945/an.113.005603.
[5] A. Cerkezkayabekir et al., Naringin Protects Viscera from Ischemia/reperfusion Injury by Regulating the Nitric Oxide Level in a Rat Model, Biotech Histochem,Vol. 92, No. 4, 2017, pp. 252-263, https://doi.org/10.1080/10520295.2017.1305499.
[6] D. Singh, K. Chopra, The Effect of Naringin, a Bioflavonoid on Ischemia-reperfusion Induced Renal Injury in Rats, Pharmacol Res, Vol. 50, No. 2, 2004, pp. 187-93, https://doi.org/10.1016/j.phrs. 2004.01.007.
[7] F. Li et al., Naringin Attenuates Rat Myocardial Ischemia/reperfusion Injury Via PI3K/Akt Pathway-mediated Inhibition of Apoptosis, Oxidative Stress and Autophagy, Exp Ther Med, Vol. 22, No. 2, 2021, pp. 811, https://doi.org/ 10.3892/etm.2021.10243.
[8] R C. Chen et al., Naringin Protects Against Anoxia/reoxygenation-induced Apoptosis in H9c2 Cells Via the Nrf2 Signaling Pathway, Food Funct, Vol. 6, No. 4, 2015, pp. 1331-44, https://doi.org/10.1039/c4fo01164c.
[9] V. T. Thu et al., Majonoside-R2 Extracted from Vietnamese Ginseng Protects H9C2 Cells Against Hypoxia/reoxygenation Injury Via Modulating Mitochondrial Function and Biogenesis, Bioorg Med Chem Lett, Vol. 36, 2021, pp. 127814, https://doi.org/10.1016/j.bmcl.2021.127814.
[10] J. Chen et al., Naringin Inhibits ROS-activated MAPK Pathway in High Glucose-induced Injuries in H9c2 Cardiac Cells, Basic Clin Pharmacol Toxicol, Vol. 114, No. 4, 2014, pp. 293-304, https://doi.org/10.1111/bcpt.12153.
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[12] J. Zhou, L. Xia, Y. Zhang, Naringin Inhibits Thyroid Cancer Cell Proliferation and Induces Cell Apoptosis Through Repressing PI3K/AKT Pathway Pathol Res Pract, Vol. 215, No. 12, 2019, pp. 152707, https://doi.org/10.1016/j.prp. 2019.152707.
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[14] J. Feng et al., Naringin Attenuates Cerebral Ischemia-Reperfusion Injury Through Inhibiting Peroxynitrite-Mediated Mitophagy Activation, Mol Neurobiol, Vol. 55, No. 12, 2018, pp. 9029-9042, https://doi.org/10.1007/s12035-018-1027-7.
[15] L. J. Sun, et al., Naringin Mitigates Myocardial Strain and the Inflammatory Response in Sepsis-induced Myocardial Dysfunction through Regulation of PI3K/AKT/NF-κB Pathway, Int Immunopharmacol, Vol. 75, 2019, pp. 105782, https://doi.org/10.1016/ j.intimp.2019.105782.
[16] M. Cavia-Saiz et al., Antioxidant Properties, Radical Scavenging Activity and Biomolecule Protection Capacity of Flavonoid Naringenin and Its Glycoside Naringin: A Comparative Study, J. Sci Food Agric, Vol. 90, No. 7, 2010, pp. 1238-44, https://doi.org/10.1002/jsfa.3959.
[17] L. J. Sun et al., Layer-specific Strain for Assessing the Effect of Naringin on Systolic Myocardial Dysfunction Induced by Sepsis and Its Underlying Mechanisms, The Journal of International Medical Research, Vol. 49, No. 1, 2021, pp. 300060520986369-300060520986369, https://doi.org/10.1177/0300060520986369.
[18] J. Dudek, Role of Cardiolipin in Mitochondrial Signaling Pathways. Frontiers in Cell and Developmental Biology, Vol. 5, No. 90, 2017, https://doi.org/10.3389/fcell.2017.00090.
[19] G. Paradies et al., Cardiolipin Alterations and Mitochondrial Dysfunction in Heart Ischemia/reperfusion Injury, Clinical Lipidology, Vol. 10, No. 5, 2015, pp. 415-429, https://doi.org/10.2217/clp.15.31.
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[21] U. Schlattner et al., Mitochondrial Kinases and Their Molecular Interaction with Cardiolipin, Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1788, No. 10, 2009, pp. 2032-2047, https://doi.org/10.1016/j.bbamem.2009.04.018.
[22] M. N. Sack, Mitochondrial Depolarization and the Role of Uncoupling Proteins in Ischemia Tolerance, Cardiovascular Research, Vol. 72, No. 2, 2006, pp. 210-219, https://doi.org/10.1016/ j.cardiores.2006.07.010.
[23] L. D. Zorova et al., Mitochondrial Membrane Potential, Analytical Biochemistry, Vol. 552, 2018, pp. 50-59, https://doi.org/10.1016/j.ab. 2017.07.009.