Study on the protective effect of green tea against bisphenol A- induced amyloid aggregation in the brain of male albino rats.

  • Dhuha Q. Kamil Department of medical lab techniques, Erbil polytechnic university,Shaqlawa technical institute, Erbil,Iraq
  • Khabat A. Ali Department of biology, college of education, Salahaddin university-Erbil ,Kurdistan Region, Iraq.
Keywords: BPA, brain, green tea extract, oxidative stress, MDA, SOD, amyloid


    Bisphenol A (BPA) has been used in the plastic industry and widely distributed in the environment. Green tea extract has been known for its antioxidant activity. This study was designed to investigate the protective efficacy of green tea against brain amyloid aggregation which induced by BPA. Twenty male albino rats were exposed to BPA (500 mg/kg); green tea ethanolic extracts in two dose levels 150 and 300 mg/kg respectively plus BPA. After 60 days, malondialdehyde (MDA), superoxide dismutase (SOD)  in the brain were measured besides body and brain weights. BPA exposed groups showed a significant reduction (P<0.05) in the final body weight, with a non-significant reduction in absolute brain weight. BPA was also increased oxidative stress in the brain of the treated rats besides histological changes with amyloid deposition in the brain detected by congo red staining technique. Treatment with green tea ethanol extracts were protected animal brains against adverse effects caused by BPA and reduced oxidative stress in a dose-dependent manner. that may be related to enriched ingredients that  have been found in the extract.


ABDEL-RAHMAN, H. G., A., H. M., ABDELRAZEK, H. M. A., ZEIDAN,D.W., MOHAMED, R. M. & ABDELAZIM,A. M. 2018. Lycopene: Hepatoprotective and Antioxidant Effects toward Bisphenol A-Induced Toxicity in Female Wistar Rats. Oxidative Medicine and Cellular Longevity

AUS DEM SIEPEN, F., BAUER, R., AURICH, M., BUSS, S. J., STEEN, H., ALTLAND, K., KATUS, H. A. & KRISTEN, A. V. 2015. Green tea extract as a treatment for patients with wild-type transthyretin amyloidosis: an observational study. Drug Des Devel Ther, 9, 6319-25.
BABA, K., OKADA, K., KINOSHITA, T. & IMAOKA, S. 2009. Bisphenol A disrupts Notch signaling by inhibiting gamma-secretase activity and causes eye dysplasia of Xenopus laevis. Toxicol Sci, 108, 344-55.
BANCROFT, J., STEVENS, A. & AND TURNER, D. 1990. Theory and Practice of Histological Techniques, Churchill-Livingstone
BEHL, C., DAVIS, J. B., LESLEY, R. & SCHUBERT, D. 1994. Hydrogen peroxide mediates amyloid beta protein toxicity. Cell, 77, 817-27.
BELL, R. D., DEANE, R., CHOW, N., LONG, X., SAGARE, A., SINGH, I., STREB, J. W., GUO, H., RUBIO, A., VAN NOSTRAND, W., MIANO, J. M. & ZLOKOVIC, B. V. 2009. SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular cells. Nat Cell Biol, 11, 143-53.
CABRERA, C., GIMENEZ, R. & LOPEZ, M. C. 2003. Determination of tea components with antioxidant activity. J Agric Food Chem, 51, 4427-35.
CHAWSHEEN, M. A. H. & AZIZ, F. M. 2013 Synergistic Neurotoxic Effect of Di-n-butylphthalate on methomyl treated rats. ZANCO Journal of Pure and Applied Sciences, 24(2), 1-10.
CHEN, Y. K., CHEUNG, C., REUHL, K. R., LIU, A. B., LEE, M. J., LU, Y. P. & YANG, C. S. 2011. Effects of green tea polyphenol (-)-epigallocatechin-3-gallate on newly developed high-fat/Western-style diet-induced obesity and metabolic syndrome in mice. J Agric Food Chem, 59, 11862-71.
ELŻBIETA SIKORA, J. O. 2011. Study of antioxidant properties of green tea extract. CHEMIK 2011, , 65, 10, , 968-973.
FANG, SHI, Q., GUO, Y., HUA, J., WANG, X. & ZHOU, B. 2016a. Enhanced Bioconcentration of Bisphenol A in the Presence of Nano-TiO2 Can Lead to Adverse Reproductive Outcomes in Zebrafish. Environ Sci Technol, 50, 1005-13.
FANG, F., GAO, Y., WANG, T., CHEN, D., LIU, J., QIAN, W., CHENG, J., GAO, R., WANG, J. & XIAO, H. 2016b. Insulin signaling disruption in male mice due to perinatal bisphenol A exposure: Role of insulin signaling in the brain. Toxicol Lett, 245, 59-67.
FUJIWARA, Y., MIYAZAKI, W., KOIBUCHI, N. & AND KATOH, T. 2018. The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line. Front Endocrinol (Lausanne), 9, 24.
GALLEANO, M., VERSTRAETEN, S. V., OTEIZA, P. I. & FRAGA, C. G. 2010. Antioxidant actions of flavonoids: thermodynamic and kinetic analysis. Arch Biochem Biophys, 501, 23-30.
GARCIA-ESPINEIRA, M. C., TEJEDA-BENITEZ, L. P. & OLIVERO-VERBEL, J. 2018. Toxic Effects of Bisphenol A, Propyl Paraben, and Triclosan on Caenorhabditis elegans. Int J Environ Res Public Health, 15.
GONG, H., ZHANG, X., CHENG, B., SUN, Y., LI, C., LI, T., ZHENG, L. & HUANG, K. 2013. Bisphenol A accelerates toxic amyloid formation of human islet amyloid polypeptide: a possible link between bisphenol A exposure and type 2 diabetes. PLoS One, 8, e54198.
HERNANDEZ-RODRIGUEZ, G., ZUMBADO, M., LUZARDO, O. P., MONTERDE, J. G., BLANCO, A. & BOADA, L. D. 2007. Multigenerational study of the hepatic effects exerted by the consumption of nonylphenol- and 4-octylphenol-contaminated drinking water in Sprague-Dawley rats. Environ Toxicol Pharmacol, 23, 73-81.
HUGH S. TAYLOR, M. D. 2008. Endocrine Disruptors Affect Developmental Programming of HOX Gene Expression. Fertil Steril 89(2 Suppl): e57–e58.
ISMAIL, T. F. 2017. Histological Effect of Methomyl on Rat Brain and Testis. ZANCO Journal of Pure and Applied Sciences, 29, 161-7.
JURADO-CORONEL, J. C., AVILA-RODRIGUEZ, M., ECHEVERRIA, V., HIDALGO, O. A., GONZALEZ, J., ALIEV, G. & BARRETO, G. E. 2016. Implication of Green Tea as a Possible Therapeutic Approach for Parkinson Disease. CNS Neurol Disord Drug Targets, 15, 292-300.
KATIYAR, S. K. & ELMETS, C. A. 2001. Green tea polyphenolic antioxidants and skin photoprotection (Review). Int J Oncol, 18, 1307-13.
KE, C., LIU, X., ZUO, H., ZHAO, J., YANG, X. & YUAN, J. 2013. The oxidative damage of Bisphenol A on the organs of the mice. Health, 05, 1190-1194.
KHADRAWY, Y. A., NOOR, N. A., MOURAD, I. M. & EZZ, H. S. 2016. Neurochemical impact of bisphenol A in the hippocampus and cortex of adult male albino rats. Toxicol Ind Health, 32, 1711-9.
LANG, I. A., GALLOWAY, T. S., SCARLETT, A., HENLEY, W. E., DEPLEDGE, M., WALLACE, R. B. & MELZER, D. 2008. Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA, 300, 1303-10.
LU, M.-J. & CHEN, C. 2008. Enzymatic modification by tannase increases the antioxidant activity of green tea. Food Research International, 41, 130-137.
MANDEL, S., WEINREB, O., AMIT, T. & YOUDIM, M. B. 2004. Cell signaling pathways in the neuroprotective actions of the green tea polyphenol (-)-epigallocatechin-3-gallate: implications for neurodegenerative diseases. J Neurochem, 88, 1555-69.
MENDELSON, S. D. 2009. Beyond Alzheimer's How to avoid the modern epidemic of dimentia M. evan , Lanham. Newyork.Boulder. Toronto.plymouth, UK , Rowman &littlefield publishing group,Inc., 128-129.
MERELES, D., WANKER, E. E. & KATUS, H. A. 2008. Therapy effects of green tea in a patient with systemic light-chain amyloidosis. Clin Res Cardiol, 97, 341-4.
MORGAN, A. M., EL-BALLAL, S. S., EL-BIALY, B. E. & EL-BORAI, N. B. 2014. Studies on the potential protective effect of cinnamon against bisphenol A- and octylphenol-induced oxidative stress in male albino rats. Toxicol Rep, 1, 92-101.
NAKAGAWA, Y. & TAYAMA, S. 2000. Metabolism and cytotoxicity of bisphenol A and other bisphenols in isolated rat hepatocytes. Arch Toxicol, 74, 99-105.
NEGRI-CESI, P. 2015. Bisphenol A Interaction With Brain Development and Functions. Dose-Response:An International Journal, 1-12.
NEHLIG, A. 2013. The neuroprotective effects of cocoa flavanol and its influence on cognitive performance. Br J Clin Pharmacol, 75, 716-27.
NISHIKAWA, M., IWANO, H., YANAGISAWA, R., KOIKE, N., INOUE, H. & YOKOTA, H. 2010. Placental transfer of conjugated bisphenol A and subsequent reactivation in the rat fetus. Environ Health Perspect, 118, 1196-203.
OBREGON, D. F., REZAI-ZADEH, K., BAI, Y., SUN, N., HOU, H., EHRHART, J., ZENG, J., MORI, T., ARENDASH, G. W., SHYTLE, D., TOWN, T. & TAN, J. 2006. ADAM10 activation is required for green tea (-)-epigallocatechin-3-gallate-induced alpha-secretase cleavage of amyloid precursor protein. J Biol Chem, 281, 16419-27.
PAL, S., SARKAR, K., NATH, P. P., MONDAL, M., KHATUN, A. & PAUL, G. 2017. Bisphenol S impairs blood functions and induces cardiovascular risks in rats. Toxicology reports, 4, 560-565.
PERERA, F., NOLTE, E. L. R., WANG, Y., MARGOLIS, A. E., CALAFAT, A. M., WANG, S., GARCIA, W., HOEPNER, L. A., PETERSON, B. S., RAUH, V. & HERBSTMAN, J. 2016. Bisphenol A exposure and symptoms of anxiety and depression among inner city children at 10–12 years of age. Environmental Research, 151, 195-202.
PRASANSUKLAB, A. & TENCOMNAO, T. 2013. Amyloidosis in Alzheimer's Disease: The Toxicity of Amyloid Beta (A β ), Mechanisms of Its Accumulation and Implications of Medicinal Plants for Therapy. Evidence-based complementary and alternative medicine : eCAM, 2013, 413808-413808.
RASUL, K. H., MAHMOOD, N. M. S., HAMAD, S. H. & HASSAN, D. H. 2016. Histological Changes of Liver, Kidney and Brain in Uninephrectomized Male Rats Exposed to Fluoxetine. ZANCO Journal of Pure and Applied Sciences, 28 601-626.
REZAI-ZADEH K, SHYTLE D, SUN N, MORIT, HOU H, JEANNITON D, EHRHART J, TOWNSEND K, ZENG J, MORGAN D, HARDYJ, TOWN T & ., T. J. 2005. Green tea epi-gallocatechin-3-gallate (EGCG) modu-latesamyloidprecursorproteincleavage and reduces cerebral amyloi-dosis in Alzheimer transgenic mice. JNeurosci 25, 8807–8814
RIEGSECKER, S., WICZYNSKI, D., KAPLAN, M. J. & AHMED, S. 2013. Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation in rheumatoid arthritis. Life Sci, 93, 307-12.
SEERAM, N. P., HENNING, S. M., NIU, Y., LEE, R., SCHEULLER, H. S. & HEBER, D. 2006. Catechin and caffeine content of green tea dietary supplements and correlation with antioxidant capacity. J Agric Food Chem, 54, 1599-603.
SWINTON, E., DE FREITAS, E., SWINTON, C., SHYMANSKY, T., HILES, E., ZHANG, J., ROTHWELL, C. & LUKOWIAK, K. 2018. Green tea and cocoa enhance cognition in Lymnaea. Commun Integr Biol, 11, e1434390.
VAN PRAAG, H., LUCERO, M. J., YEO, G. W., STECKER, K., HEIVAND, N., ZHAO, C., YIP, E., AFANADOR, M., SCHROETER, H., HAMMERSTONE, J. & GAGE, F. H. 2007. Plant-derived flavanol (-)epicatechin enhances angiogenesis and retention of spatial memory in mice. J Neurosci, 27, 5869-78.
YOSHIDA, H., ISHIKAWA, T., HOSOAI, H., SUZUKAWA, M., AYAORI, M., HISADA, T., SAWADA, S., YONEMURA, A., HIGASHI, K., ITO, T., NAKAJIMA, K., YAMASHITA, T., TOMIYASU, K., NISHIWAKI, M., OHSUZU, F. & NAKAMURA, H. 1999. Inhibitory effect of tea flavonoids on the ability of cells to oxidize low density lipoprotein. Biochem Pharmacol, 58, 1695-703.
YUAN, F., DONG, H., FANG, K., GONG, J. & LU, F. 2018. Effects of green tea on lipid metabolism in overweight or obese people: A meta-analysis of randomized controlled trials. Mol Nutr Food Res, 62.
ZECHNER, R., ZIMMERMANN, R., EICHMANN, T. O., KOHLWEIN, S. D., HAEMMERLE, G., LASS, A. & MADEO, F. 2012. FAT SIGNALS--lipases and lipolysis in lipid metabolism and signaling. Cell Metab, 15, 279-91.
ZUO, Y. & ZHU, A. Z. 2014. Simultaneous identification and quantification of 4-cumylphenol, 2,4-bis-(dimethylbenzyl)phenol and bisphenol A in prawn Macrobrachium rosenbergii. Chemosphere, 107, 447-453.
How to Cite
Q. Kamil, D. and A. Ali, K. (2020) “Study on the protective effect of green tea against bisphenol A- induced amyloid aggregation in the brain of male albino rats.”, Zanco Journal of Pure and Applied Sciences, 32(2), pp. 192-202. doi: 10.21271/ZJPAS.32.2.20.
Biology and Medical Researches