EFFECTS OF BISPHENOL A ON NEONATAL CARDIOMYOCYTES BEATING RATE AND MORPHOLOGY
DOI:
https://doi.org/10.11113/jt.v80.12286Keywords:
Bisphenol A, cardiomyocytes, cells morphology, beating rates, cytotoxicityAbstract
Bisphenol A (BPA) has been utilised excessively at a global capacity of 2.9 billion kg/year. It is widely used in manufacturing polycarbonate polymers and epoxy resins. Hence, humans are potentially exposed to this chemical substance in their daily life. As a typical endocrine disruptor, BPA exhibits detectable hormone-like properties. Many studies have been linking BPA exposure in humans with the risk of developing cardiovascular disease, however the direct exposure of BPA on cardiomyocytes beating rates and morphology have not been entirely explored. Therefore, in this study, we aimed to investigate the effects of BPA on cells structure and function of neonatal rat cardiomyocytes culture. Cardiomyocytes were isolated from 0 to 2 days old newborn rats and treated with 0.001 to 100 µM concentration of BPA. All cardiomyocytes were subjected to immunostaining, beating frequency assessment assay, MTS assay and Scanning Electron microscopy (SEM). In immunostaining, cardiomyocytes showed positive staining for F-actin. This staining allows identification of the cells thus differentiate cardiomyocytes from other cell types. Significance effects of BPA on cardiomyocytes were observed in MTS assay (p<0.05) and beating rates (p<0.01). Significant reduction (48%-64%, ± 1.5280) was observed in beating rate of cardiomyocytes exposed to 0.1 to 100 µM of BPA. Meanwhile in MTS assay, significant reduction (54%, 0.067 ± 0.0026) in cell viability was observed in cells exposed to 0.1 µM of BPA only. Interestingly, under SEM, cardiomyocytes showed altered cell surface homogeneity after BPA exposure. Exposure of 0.1 to 100 µM BPA lead to flatten of cardiomyocytes cell surface and blurring of the cell borders. This study offers an in vitro evidence of BPA effects on cardiomyocytes morphology and beating rates, thus suggest the potential adverse effect of BPA exposure. However, further investigation would be required to understand how BPA effects normal cells morphology and beating rates of heart cells.
References
Bondesson, M., et al. 2009. A CASCADE of Effects of Bisphenol A. Reprod Toxicol. 28(4): 563-7.
Vandenberg, L. N., et al. 2007. Human Exposure to Bisphenol A (BPA). Reprod Toxicol. 24(2): 139-77.
Dodds, E. C. 1936. Chemical Structure in Relationship to Hormone and Biological Activity. Helvetica Chimica Acta. 19(1): E49-E58.
Wolfgang Vo¨lkel, T.C., , Gyo¨rgy A. Csana´dy, Johannes G. Filser, and Wolfgang Dekant. 2002. Metabolism and Kinetics of Bisphenol A in Humans at Low Doses Following Oral Administration. Chem Resource Toxicology. 15(10): 1281-1287.
Chia-Yu Chu, A. P. N., Chee-Ching Sun and Shiou-Hwa Jee. 2010. Concomitant Contact Allergy to the Resins, Reactive Diluents and Hardener of a Bisphenol A/F-based Epoxy Resin in Subway Construction Workers. 2006(54): 131-139.
Nakamura, D., et al. Bisphenol A May Cause Testosterone Reduction by Adversely Affecting Both Testis and Pituitary Systems Similar to Estradiol. Toxicol Lett. 194(1-2): 16-25.
Li, D. et al. 2010. Occupational Exposure to Bisphenol-A (BPA) and the Risk of Self-reported Male Sexual Dysfunction. Hum Reprod. 25(2): 519-27.
M. A. MartÃnez, J. R., R. Prasad Sharma, M. Nadal, M. Schuhmachera, V. Kumara. 2017. Prenatal Exposure Estimation of BPA and DEHP using Integrated External and Internal Dosimetry: A Case Study. Environmental Research. 158: 566-575.
Wee, S. Y. and A. Z. Aris. 2017. Endocrine Disrupting Compounds in Drinking Water Supply System and Human Health Risk Implication. Environ Int. 106: 207-233.
Salian, S., T. Doshi, and G. Vanage. 2011. Perinatal Exposure of Rats to Bisphenol a Affects Fertility of Male Offspring--An Overview. Reprod Toxicol. 31(3): 359-62.
Wada, K., et al. 2007. Life Style-Related Diseases of the Digestive System: Endocrine Disruptors Stimulate Lipid Accumulation in Target Cells Related to Metabolic Syndrome. Journal of Pharmacological Sciences. 105(2): 133-137.
Alonso-Magdalena, P., I. Quesada, and A. Nadal. 2011. Endocrine Disruptors in the Etiology of Type 2 Diabetes Mellitus. Nat Rev Endocrinol. 7(6): 346-53.
Ben-Jonathan, N., E. R. Hugo, and T. D. Brandebourg. 2009. Effects of Bisphenol a on Adipokine Release from Human Adipose Tissue: Implications for the Metabolic Syndrome. Mol Cell Endocrinol. 304(1-2): 49-54.
Hugo, E. R., et al. 2008. Bisphenol a at Environmentally Relevant Doses Inhibits Adiponectin Release from Human Adipose Tissue Explants and Adipocytes. Environ Health Perspect. 116(12): 1642-7.
Singh, S. and S. S. Li. 2012. Bisphenol A and Phthalates Exhibit Similar Toxicogenomics and Health Effects. Gene. 494(1): 85-91.
Fenichel, P., N. Chevalier, and F. Brucker-Davis. 2013. Bisphenol A: An Endocrine and Metabolic Disruptor. Ann Endocrinol (Paris). 74(3): 211-20.
Carwile, J. L., & Michels, K. B. 2011. Urinary Bisphenol A and Obesity : NHANES 2003 – 2006 $. 111: 825-830. https://doi.org/10.1016/j.envres.2011.05.014.
Ranciere, F., et al. 2015. Bisphenol A and the Risk of Cardiometabolic Disorders: A Systematic Review with Meta-analysis of the Epidemiological Evidence. Environ Health. 14: 46.
Izzotti, A. and A. Pulliero. 2014. The Effects of Environmental Chemical Carcinogens on the microRNA Machinery. Int J Hyg Environ Health. 217(6): 601-27.
Shankar, A., Teppala, S., & Sabanayagam, C. 2012. Bisphenol A and Peripheral Arterial Disease: Results from the NHANES. Environmental Health Perspectives. 120(9): 1297-1300. https://doi.org/10.1289/ehp.1104114.
Ljunggren, S. A., et al. 2016. Altered Heart Proteome in Fructose-fed Fisher 344 Rats Exposed to Bisphenol A. Toxicology. 347-349: 6-16.
Sheikh Abdul Kadir, S. H., et al. 2010. Bile Acid-induced Arrhythmia is Mediated by Muscarinic M2 Receptors in Neonatal Rat Cardiomyocytes. PLoS One. 5(3): e9689.
Liang, Q., et al. 2014. Cellular Mechanism of the Nonmonotonic Dose Response of Bisphenol a in Rat Cardiac Myocytes. Environ Health Perspect. 122(6): 601-8.
Zhou, R., et al. 2017. Interactions between Three Typical Endocrine-disrupting Chemicals (EDCs) in Binary Mixtures Exposure on Myocardial Differentiation of Mouse Embryonic Stem Cell. Chemosphere. 178: 378-383.
Posnack, N.G., et al. 2014. Bisphenol A Exposure and Cardiac Electrical Conduction in Excised Rat Hearts. Environ Health Perspect. 122(4): 384-90.
Ramadan, M., Sherman, M., Jaimes Iii, R., Chaluvadi, A., Swift, L., & Gillum Posnack, N. 2018. Disruption of Neonatal Cardiomyocyte Physiology Following Exposure to Bisphenol-a. https://doi.org/10.1038/s41598-018-25719-8.
Hu, Y., et al. 2016. Bisphenol A, An Environmental Estrogen-like Toxic Chemical, Induces Cardiac Fibrosis by Activating the ERK1/2 Pathway. Toxicol Lett. 250-251: 1-9.
Bolli, A., et al. 2008. Laccase Treatment Impairs Bisphenol A-Induced Cancer Cell Proliferation Affecting Estrogen Receptor Alpha-dependent Rapid Signals. IUBMB Life. 60(12): 843-52.
Tayama, Y. N. á. S. 2000. Metabolism and Cytotoxicity of Bisphenol A and Other Bisphenols in Isolated Rat Hepatocytes. Arch Toxicology. 74: 99-105.
Angle, B. M., et al. 2013. Metabolic Disruption in Male Mice Due to Fetal Exposure to Low But Not High Doses of Bisphenol A (BPA): Evidence for Effects on Body Weight, Food Intake, Adipocytes, Leptin, Adiponectin, Insulin and Glucose Regulation. Reprod Toxicol. 42: 256-68.
Clement, F., et al. 2017. Long-term Exposure to Bisphenol A Or Benzo(A)Pyrene Alters the Fate of Human Mammary Epithelial Stem Cells in Response to BMP2 and BMP4, by Pre-activating BMP Signaling. Cell Death Differ. 24(1): 155-166.
Downloads
Published
Issue
Section
License
Copyright of articles that appear in Jurnal Teknologi belongs exclusively to Penerbit Universiti Teknologi Malaysia (Penerbit UTM Press). This copyright covers the rights to reproduce the article, including reprints, electronic reproductions, or any other reproductions of similar nature.