Vitamin E Attenuates Cardiomyopathy Via Alleviation of Autophagic Stress


  • Eman Farrag Lecturer of clinical Pharmacology, Faculty of Medicine Mansoura University, Egypt.
  • Eman Ali Abdelrazik Lecturer of Forensic Medicine and Clinical Toxicology, Faculty of Medicine Mansoura Univerasity, Egypt.
  • Zainb Abdallah Mahmoud Lecturer of Physiology, Faculty of Medicine Mansoura University, Egypt.
  • Hend Mohammed Mohammed Hassan Lecturer of Anatomy and Embryology, Faculty of Medicine Mansoura University, Egypt


Cardiomyopathy, Bisphenol A, Vitamin E, oxidative stress, autophagy, LC3, P62


Introduction: Vitamin E (Vit E) is well known antioxidant. Bisphenol A (BPA), widely used industrial chemical product, is associated with increased risk for cardiac diseases to identify the potential protective effect of Vit E on BPA induced cardiomyopathy by alleviation of oxidative and autophagic stress through its antioxidant effect. Materials and Methods: Twenty –four adult male rates were used in the study. They were randomly divided into 4 groups; negative control, vit E positive control, BPA, and vit E treated group. All chemicals were given orally via gastric gavage for 14 days. Rats were sacrificed and their hearts were dissected out. Serum, cardiac homogenates, and cardiac tissues were obtained for biochemical and histopathological evaluation. Results: There were significant increase in serum DH and CK-MB, tissue homogenates showed elevated levels of NO and MDA and decreased level of GSH in BPA group. Immunohistopathological evaluation of autophagic mediators showed significant increase in LC3 and P62 in BPA group. On Histological examination, there was pathological alteration in BPA group compared to normal group. Vit E administration showed significant improvement in cardiac enzymes and oxidative stress. Also, alleviation of autophagic process and restoration of the myocardial architecture with reduction of the fibrous tissue were observed with vit E administration. Conclusion: These results demonstrate that vitamin E exhibit substantial protective effects in BPA induced cardiotoxicity by attenuating inflammation, oxidative stress, and alleviation the autophagic process.


. J. Du, Y. Liu, & J. Fu, Autophagy, Myocarditis, and Cardiomyopathy. In Autophagy: Biology and Diseases. 229-235, 2020

. H. Saini, S. Tabtabai, J. Stone, et al. Pathophysiology of Cardiomyopathies. In Cellular and Molecular Pathobiology of Cardiovascular Disease. 101-119. 2014.‏

. R. Rezg, S. El-Fazaa, N. Gharbi, et al. Bisphenol A and human chronic diseases: Current evidences, possible mechanisms, and future perspectives. Environ. Int. 64, 83–90. 2014.

. X. Gao, & S. Wang. Impact of bisphenol A on the cardiovascular system—Epidemiological and experimental evidence and molecular mechanisms. International journal of environmental research and public health. 11(8), 8399-8413.‏ 2014.

. A. Priego, R., G. Parra, S. Mas, et al. Bisphenol A Modulates Autophagy and Exacerbates Chronic Kidney Damage in Mice. International Journal of Molecular Sciences 22(13), 7189. 2021.

. T. Zech, Singh, S. Schlossarek, et al. Autophagy in cardiomyopathies. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 1867(3), 118432.‏ 2020.

. J.N. Keller, E. Dimayuga, E., Q. Chen, Q. et al. Autophagy, proteasomes, lipofuscin, and oxidative stress in the aging brain. Int. J. Biochem. Cell Biol. 36, 2376–2391. 2004.

. C.T. Chu, Autophagic stress in neuronal injury and disease. J. Neuropathol. Exp. Neurol. 65, 423–432. 2006.

. P. Tannous, H. Zhu, J.L. Johnstone, et al. Autophagy is an adaptive response in desmin-related cardiomyopathy. Proceedings of the National Academy of Sciences. 105(28), 9745-9750.‏ 2008.

. M. Sandri, & J. Robbins, Proteotoxicity: an underappreciated pathology in cardiac disease. Journal of molecular and cellular cardiology. 71, 3-10.‏ 2014.

. Y. Zhao, W. Zhang, W., Q. Jia, et al. High dose vitamin E attenuates diabetic nephropathy via alleviation of autophagic stress. Frontiers in physiology. 9, 1939.‏ 2019.

. M.M. Abdel-Daim, & A. Abdeen, A. Protective effects of rosuvastatin and vitamin E against fipronil-mediated oxidative damage and apoptosis in rat liver and kidney. Food and chemical toxicology. 114, 69-77.‏ 2018.

. A. Vanani, M. Mahdavinia, M.=Shirani, et al. Protective effects of quercetin against oxidative stress induced by bisphenol-A in rat cardiac mitochondria. Environmental Science and Pollution Research. 1-10.‏2020.

. H. Waynforth, P. Brain, M Sharpe, T. et al. Good practice guidelines. Administration of substances (rat, mouse, guinea pig, rabbit). Association, LAS (Ed). 1, 4. 1998.

. G. Gong, L HE, & G. Huang, Study on the relationship of the CK, CK-MB and hs-cTnT levels and infarct size in acute myocardial infarction. Experimental and Laboratory Medicine. 06. 2012.

. G. Schumann, R. Bonora, F. Ceriotti F. et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. Part 3. Reference procedure for the measurement of catalytic concentration of lactate dehydrogenase. Clin Chem Lab Med. 40(6):643-8. 2002.

. X. Chen, D. Cho, P. Yang. Double staining immunohistochemistry. N Am J MedSci. 2(5): 241–245. 2010.

. S. Kazemi,., S. Mousavi, F. Aghapour, F. et al. Induction effect of bisphenol A on gene expression involving hepatic oxidative stress in rat. Oxidative medicine and cellular longevity, 2016.

. J.Pant, & S.B. Deshpande, Acute toxicity of bisphenol A in rats. . 50;6.425-429. 2012.

. H. S. Ezz, Y.A. Khadrawy, & I.M. Mourad, The effect of bisphenol A on some oxidative stress parameters and acetylcholinesterase activity in the heart of male albino rats. Cytotechnology. 67(1), 145-155. 2015.

. M. J. Khodayar, H. Kalantari, M. Mahdavinia M, et al. Protective effect of naringin against BPA-induced cardiotoxicity through prevention of oxidative stress in male Wistar rats. Drug Chem Toxicol. 1–11. 2018.

. C. Han, & Y. C.Hong. Bisphenol A, hypertension, and cardiovascular diseases: Epidemiological, laboratory, and clinical trial evidence. Current Hypertension Reports. 18(2), 11. 2016.

. V. Quagliariello, C. Coppola, D. G. Mita, et al. Low doses of bisphenol A have pro-inflammatory and pro-oxidant effects, stimulate lipid peroxidation and increase the cardiotoxicity of doxorubicin in cardiomyoblasts. Environmental Toxicology and Pharmacology. 69, 1– 8. 2019.

. D. Del Rio, A.J. Stewart, & N. A. Pellegrini. review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutrition, Metabolism, and Cardiovascular diseases. 15(4), 316– 328. 2005.

. H. Sies. Glutathione and its role in cellular functions. Free Radic Biol Med. 27(9–10):916–921. 1999.

. S. Khan, S. Beigh, B.P. Chaudhari, et al. Mitochondrial dysfunction induced by Bisphenol A is a factor of its hepatotoxicity in rats.Environ. Toxicol. 31, 1922–1934. 2016.

. W. Peerapanyasut, A. Kobroob, S. Palee, S. et al. Activation of sirtuin 3 and maintenance of mitochondrial integrity by N-acetylcysteine protects against bisphenol A-induced kidney and liver toxicity in rats. International journal of molecular sciences. 20(2), 267. 2019b.

. C. Quan, C.Wang, P. Duan, P. et al. Bisphenol A induces autophagy and apoptosis concurrently involving the Akt/mTOR pathway in testes of pubertal SD rats. Environmental Toxicology. 32(8), 1977– 1989. 2017.

. A. Morris. Endocrine disruptors: Does BPA disrupt autophagy in the liver? Nat. Rev. Endocrinol. 13, 250. 2017.

. N. Mizushima, T. Yoshimori, B. Levine, Methods in mammalian autophagy research. Cell. 140, 313–326. 2010.


. S. Yang, A. Zhang, T. Li, T., R. Gao, et al. Dysregulated Autophagy in Hepatocytes Promotes Bisphenol A–Induced Hepatic Lipid Accumulation in Male Mice. Endocrinology. 158(9), 2799-2812. 2017.

. S. Pankiv, T.H. Clausen, T. Lamark, et al. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. Journal of biological chemistry. 282(33), 24131-24145. 2007. AccessDOI:

. Y. Watanabe, & M. Tanaka. p62/SQSTM1 in autophagic clearance of a non-ubiquitylated substrate. Journal of cell science. 124(16), 2692-2701. 2011.

. D. Song, Y. Chen, B. Wang, B. et al. Bisphenol A inhibits autophagosome-lysosome fusion and lipid droplet degradation. Ecotoxicology and environmental safety. 183, 109492. 2019.

. E.E. Essick, & F. Sam. Oxidative stress and autophagy in cardiac disease, neurological disorders, aging and cancer. Oxidative Medicine and Cellular Longevity. 3(3), 168– 177. 2010.

. C. Fang, B. Ning, A. B. Waqar, A. B. et al. Bisphenol A exposure enhances atherosclerosis in WHHL rabbits. PLoS One. 9(10), e110977. 2014.

. J. K. Hwang, K. H. Min, K. H. Choi, et al. Bisphenol A reduces differentiation and stimulates apoptosis of osteoclasts and osteoblasts. Life Sciences. 93(9–11), 367– 372. 2013.

. J. Guo, M. H. Zhao, K. T. Shin, et al. The possible molecular mechanisms of bisphenol A action on porcine early embryonic development. Scientific reports. 7(1), 1-9. 2017.

. N.G. Bahey, H.O. Abd Elaziz, & K.E. Gadalla, Potential toxic effect of bisphenol A on the cardiac muscle of adult rat and the possible protective effect of Omega-3: A histological and immunohistochemical study. Journal of microscopy and ultrastructure. 7(1), 1- 10. 2019. 4103/JMAU.JMAU_53_18.

. J. A. Kendziorski and S.M. Belcher, Strain-specific induction of endometrial periglandular fibrosis in mice exposed during adulthood to the endocrine disrupting chemical bisphenol A. Reprod. Toxicol. 58, 119–130. 2015.

. S. E. Elswefy, F. R. Abdallah, H. H. Atteia, et al. Inflammation, oxidative stress, and apoptosis cascade implications in bisphenol A-induced liver fibrosis in male rats. Int. J. Exp. Pathol. 97, 369–379. 2016.

. K. A. Bruno, J. E. Mathews, A. L. Yang, et al. BPA alters estrogen receptor expression in the heart after viral infection activating cardiac mast cells and T cells leading to perimyocarditis and fibrosis. Frontiers in endocrinology. 10, 598.‏ 2019.

. F. Galli, A. Azzi, M. Birringer, et al. Vitamin E: Emerging aspects and new directions. Free Radical Biology and Medicine. 102, 16-36.‏ 2017.

. N. Hadi, N.G.Yousif, F.G. Al-Amran et al. Vitamin E and telmisartan attenuates doxorubicin induced cardiac injury in rat through down regulation of inflammatory response. BMC Cardiovasc Disord. 12:63. 2012.

. T. Donia, S. Eldaly, & E.M. Ali. Ameliorating oxidative stress and inflammation by Hesperidin and vitamin E in doxorubicin induced cardiomyopathy. Turkish Journal of Biochemistry. 44(2), 207-217. 2019.

. Janero, D. R. Therapeutic potential of vitamin E against myocardial ischemic-reperfusion injury. Free Radical Biology and Medicine. 1991; 10(5), 315-324.

. P. C. Badgujar, N. N. Pawar, G. A. Chandratre, G. A. et al. Fipronil induced oxidative stress in kidney and brain of mice: protective effect of vitamin E and vitamin C. Pesticide biochemistry and physiology. 118, 10-18.‏ 2015.

. H. Tai, Z. Wang, H. Gong, et al. Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence. Autophagy. 13(1), 99-113.‏ 2017.

. S. Vakili, F. Zal, Z. Mostafavi‐pour. et al. Quercetin and vitamin E alleviate ovariectomy‐induced osteoporosis by modulating autophagy and apoptosis in rat bone cells. Journal of Cellular Physiology. 236(5), 3495-3509.‏ 2021.

. R. Scherz-Shouval, & Z. Elazar. Regulation of autophagy by ROS: physiology and pathology. Trends in biochemical sciences. 36(1), 30-38.‏ 2011.

. A.M. Fayez, & M.A. Zaafan, Eicosapentaenoic acid and vitamin E against doxorubicin-induced cardiac and renal damages: role of cytochrome c and iNOS. Archives of Iranian Medicine. 21(11):502-508. 2018.

. J. Zamin, A. D. Mattos, A. Z. Mattos, et al. The vitamin E reduces liver lipoperoxidation and fibrosis in a model of nonalcoholic steatohepatitis. Arquivos de gastroenterologia. 47, 86-92. 2010.

. M. Alcalá, M., I. SánchezVera, J. Sevillano, et al. Vitamin E reduces adipose tissue fibrosis, inflammation, and oxidative stress and improves metabolic profile in obesity. Obesity. 23(8), 1598-1606. 2015.

. R. Vinayagamoorthi, Z. Bobby, & M. G. Sridhar. Antioxidants preserve redox balance and inhibit c-Jun-N-terminal kinase pathway while improving insulin signaling in fat-fed rats: evidence for the role of oxidative stress on IRS-1 serine phosphorylation and insulin resistance. Journal of endocrinology. 197(2), 287-296.‏ 2008.

. Y.Liu, W.K. Zheng, W.S. Gao, et al. Function of TGF-beta and p38 MAKP signaling pathway in osteoblast differentiation from rat adipose-derived stem cells. Eur Rev Med Pharmacol Sci. 17(12), 1611-1619.‏ 2013.




How to Cite

Farrag, E., Eman Ali Abdelrazik, Zainb Abdallah Mahmoud, & Hend Mohammed Mohammed Hassan. (2021). Vitamin E Attenuates Cardiomyopathy Via Alleviation of Autophagic Stress. International Journal of Sciences: Basic and Applied Research (IJSBAR), 60(4), 67–86. Retrieved from