Skip to main content

Advertisement

SpringerLink
Log in

The effect of bisphenol A on some oxidative stress parameters and acetylcholinesterase activity in the heart of male albino rats

  • Original Research
  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

Bisphenol A (BPA) is an endocrine disrupting chemical used on a wide range in industry. Several studies reported that BPA may cause cardiovascular disorders in humans and animals. The present study aims to investigate the effect of BPA on the heart of adult male rats. The rats received a daily oral administration of BPA (25 mg/kg for 6 weeks and 10 mg/kg for 6 and 10 weeks). It was found that BPA at the two studied doses induced a significant increase in malondialdehyde, and a significant decrease in catalase after 6 weeks. Moreover, a significant decrease in reduced glutathione and acetylcholinesterase (AchE) activity was observed after treatment with the two doses of BPA throughout the studied time intervals. The two doses (25 and 10 mg/kg) resulted in a significant decrease in nitric oxide (NO) levels after 6 and 10 weeks, respectively. A significant increase in body weight gain occurred in all animals after BPA treatment. These results suggest that BPA has cardiotoxic effects which are mediated by the oxidative stress resulting from the overproduction of free radicals, the deficiency of NO and the inhibition of AchE leading to cholinergic activation. The obesity promoting effect of BPA may also participate in the observed cardiovascular disturbances.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aebi H (1984) Catalase in vitro. Meth Enzym 105:121–126

    Article  CAS  Google Scholar 

  • Alonso-Magdalena P, Morimoto S, Ripoll C, Fuentes E, Nadal A (2006) The estrogenic effect of bisphenol A disrupts pancreatic β-cell function in vivo and induces insulin resistance. Environ Health Perspect 114:106–112

    Article  CAS  Google Scholar 

  • Alonso-Magdalena P, Ropero AB, Carrera MP, Cederroth CR, Baquié M, Gauthier BR, Nef S, Stefani E, Nadal A (2008) Pancreatic insulin content regulation by the estrogen receptor ER alpha. PLoS One 30:e2069

    Google Scholar 

  • Antoni H (1991) Function of the heart. In: Schmidt RF, Thews G (eds) Human Physiology. Springer, Berlin, pp 358–396

    Google Scholar 

  • Asano S, Tune JD, Dick GM (2010) Bisphenol A activates Maxi-K (KCa1.1) channels in coronary smooth muscle. Br J Pharmacol 160:160–170

    Article  CAS  Google Scholar 

  • Bae S, Kim JH, Lim Y-H, Park HY, Hong Y-C (2012) Associations of bisphenol A exposure with heart rate variability and blood pressure. Hypertension 60:786–793

    Article  CAS  Google Scholar 

  • Bian Q, Qian J, Xu L, Chen J, Song L, Wang X (2006) The toxic effect of 4-tert-octylphenol on the reproductive system of male rats. Food Chem Toxicol 44:1355–1361

    Article  CAS  Google Scholar 

  • Bindhumol V, Chitra KC, Mathur PP (2003) Bisphenol A induces reactive oxygen species generation in the liver of male rats. Toxicology 188:117–124

    Article  CAS  Google Scholar 

  • Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Ekong J, Needham LL (2005) Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population. Environ Health Perspect 113:391–395

    Article  CAS  Google Scholar 

  • Cannon RO (1998) Role of nitric oxide in cardiovascular disease: focus on the endothelium. Clin Chem 44:1809–1819

    CAS  Google Scholar 

  • Carlos DM, Goto S, Urata Y, Iida T, Cho S, Niwa M, Tsuji Y, Kondo T (1998) Nicardipine normalizes elevated levels of antioxidant activity in response to xanthine oxidase-induced oxidative stress in hypertensive rat heart. Free Radic Res 29:143–150

    Article  CAS  Google Scholar 

  • Chitra KC, Latchoumycandane C, Mathur PP (2003) Induction of oxidative stress by bisphenol A in the epididymal sperm of rats. Toxicology 185:119–127

    Article  CAS  Google Scholar 

  • Coors A, Jones PD, Giesy JP, Ratte HT (2003) Removal of estrogenic activity from municipal waste landfill leachate assessed with a bioassay based on reporter gene expression. Environ Sci Technol 37:3430–3434

    Article  CAS  Google Scholar 

  • Das UN (2000) Free radicals, cytokines and nitric oxide in cardiac failure and myocardial infarction. Mol Cell Biochem 215:145–152

    Article  CAS  Google Scholar 

  • Deshpande SB, Kanoo S, Alex AB (2008) Bradycardia induced by Mesobuthus tamulus scorpion venom involves muscarinic receptor-G-protein-coupled cell signaling pathways. Indian J Exp Biol 46:229–233

    CAS  Google Scholar 

  • Dhalla AK, Hill MF, Singal PK (1996) Role of oxidative stress in transition of hypertrophy to heart failure. J Am Coll Cardiol 28:506–514

    Article  CAS  Google Scholar 

  • Diamanti-Kandarakis E, Palioura E, Kandarakis SA, Koutsilieris M (2010) The impact of endocrine disruptors on endocrine targets. Horm Metab Res 42:543–552

    Article  CAS  Google Scholar 

  • Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem 82:70–77

    Article  CAS  Google Scholar 

  • Ellman GL, Courtney KD, Andres V, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  CAS  Google Scholar 

  • Erickson B (2010) FDA raises flag on bisphenol A. Chem Eng News 88:8

    Google Scholar 

  • European Union (EU) (2008) Updated European Risk Assessment Report: 4,4-isopropylidenediphenol (bisphenol-A) (CAS Number: 80-05-7, EINECS Number: 201-245-8). Available from: http://ecb.jrc.it/documents/Existingchemicals/ RISK ASSESSMENT/ADDENDUM/bisphenolaadd 325.pdf. Accessed 01. 02. 11

  • Gorun V, Proinov I, Baltescu V, Balaban G, Barzu O (1978) Modified Ellman procedure for assay of cholinesterase in crude-enzymatic preparations. Anal Biochem 86:324–326

    Article  CAS  Google Scholar 

  • Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    CAS  Google Scholar 

  • Harjai KJ (1999) Potential new cardiovascular risk factors: left ventricular hypertrophy, homocysteine, lipoprotein(a), triglycerides, oxidative stress, and fibrinogen. Ann Intern Med 131:376–386

    Article  CAS  Google Scholar 

  • Harley KG, Schall RA, Chevrier J, Tyler K, Aguirre H, Bradman A, Holland NT, Lustig RH, Calafat AM, Eskenazi B (2013) Prenatal and postnatal bisphenol A exposure and body mass index in childhood in the CHAMACOS cohort. Environ Health Perspect 121:514–520

    Article  Google Scholar 

  • Health Canada (2008) Government of Canada takes action on another chemical of concern: bisphenol A [Press release]. Available: http://www.hc-sc.gc.ca/ahc-asc/media/nr-cp/_2008/2008_59-eng.php. Accessed 25 Sept 2009

  • Hill MF, Singal PK (1996) Antioxidant and oxidative stress changes during heart failure subsequent to MI in rats. Am J Pathol 148:291–300

    CAS  Google Scholar 

  • Hill MF, Singal PK (1997) Right and left myocardial antioxidant responses during heart failure subsequent to myocardial infarction. Circulation 96:2414–2420

    Article  CAS  Google Scholar 

  • Hoover DB, Ganote CE, Ferguson SM, Blakely RD, Parsons RL (2004) Localization of cholinergic innervation in guinea pig heart by immunohistochemistry for high-affinity choline transporters. Cardiovasc Res 62:112–121

    Article  CAS  Google Scholar 

  • Hugo ER, Brandebourg TD, Woo JG, Loftus J, Alexander JW, Ben-Jonathan N (2008) Bisphenol A at environmentally relevant doses inhibits adiponectin release from human adipose tissue explants and adipocytes. Environ Health Perspect 116:1642–1647

    Article  CAS  Google Scholar 

  • Husain K (2002) Exercise conditioning attenuates the hypertensive effects of nitric oxide synthase inhibitor in rat. Mol Cell Biochem 231:129–137

    Article  CAS  Google Scholar 

  • Husain K, Hazelrigg SR (2002) Oxidative injury due to chronic nitric oxide synthase inhibition in rat: effect of regular exercise on the heart. Biochim Biophys Acta 1587:75–82

    Article  CAS  Google Scholar 

  • Ignarro LJ, Cirino G, Casini A, Napoli C (1999) Nitric oxide as a signaling molecule in the vascular system: an overview. J Cardiovasc Pharmacol 34:879–886

    Article  CAS  Google Scholar 

  • Kabuto H, Amakawa M, Shishibori T (2004) Exposure to bisphenol A during embryonic/fetal life and infancy increases oxidative injury and causes underdevelopment of the brain and testis in mice. Life Sci 74:2931–2940

    Article  CAS  Google Scholar 

  • Kanoo S, Mandal MB, Alex AB, Deshpande SB (2009) Cardiac dysrhythmia produced by Mesobuthus tamulus venom involves NO-dependent G-Cyclase signaling pathway. Naunyn Schmiedebergs Arch Pharmacol 379:525–532

    Article  CAS  Google Scholar 

  • Kawagoshi Y, Fujita Y, Kishi I, Fukunaga I (2003) Estrogenic chemicals and estrogenic activity in leachate from municipal waste landfill determined by yeast two-hybrid assay. J Environ Monit 5:269–274

    Article  CAS  Google Scholar 

  • Keith M, Geranmayegan A, Sole MJ, Kurian R, Robinson A, Omran AS, Jeejeebhoy KN (1998) Increased oxidative stress in patients with congestive heart failure. J Am Coll Cardiol 31:1352–1356

    Article  CAS  Google Scholar 

  • Kelly RA, Balligand JL, Smith TW (1996) Nitric oxide and cardiac function. Circ Res 79:363–380

    Article  CAS  Google Scholar 

  • Lakind JS, Naiman DQ (2008) Daily intake of bisphenol A and potential sources of exposure: 2005–2006 National Health and Nutrition Examination Survey. J Expo Sci Environ Epidemiol 21:272–279

    Article  Google Scholar 

  • Lang IA, Galloway TS, Scarlett A, Henley WE, Depledge M, Wallace RB, Melzer D (2008) Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA 300:1303–1310

    Article  CAS  Google Scholar 

  • Laron Z (2004) Increasing incidence of childhood obesity. Pediatr Endocrinol Rev 1:443–447

    Google Scholar 

  • Lefkowitz RJ, Hoffman BB, Taylor P (1996) Neurotransmission: the autonomic and somatic motor nervous systems. In: Hardman JG, Limbird LL, Molinoff PB, Ruddon RW, Gilman AG (eds) Goodman and Gilman’s the pharmacological basis of therapeutics, 9th edn. McGraw-Hill, New York, pp 105–139

    Google Scholar 

  • Li D-K, Miao M, Zhou Z, Wu C, Shi H, Liu X, Wang S, Yuan W (2013) Urine bisphenol-A level in relation to obesity and overweight in school-age children. PLoS ONE 8:e65399

    Article  CAS  Google Scholar 

  • Lim DS, Kwack SJ, Kim KB, Kim HS, Lee BM (2009) Potential risk of bisphenol A migration from polycarbonate containers after heating, boiling, and microwaving. J Toxicol Environ Health A 72:1285–1291

    Article  CAS  Google Scholar 

  • Lind PM, Lind L (2011) Circulating levels of bisphenol A and phthalates are related to carotid atherosclerosis in the elderly. Atherosclerosis 218:207–213

    Article  CAS  Google Scholar 

  • Mallat Z, Philip I, Lebret M, Chatel D, Maclouf J, Tedgui A (1998) Elevated levels of 8-iso-prostaglandin F2α in pericardial fluid of patients with heart failure: a potential role for in vivo oxidant stress in ventricular dilatation and progression to heart failure. Circulation 97:1536–1539

    Article  CAS  Google Scholar 

  • McCord JM (1985) Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 312:159–163

    Article  CAS  Google Scholar 

  • Melchiorri D, Reiter RJ, Sewerynek E, Hara M, Chen L, Nistico G (1996) Paraquat toxicity and oxidative damage. Reduction by melatonin. Biochem Pharmacol 51:1095–1099

    Article  CAS  Google Scholar 

  • Melzer D, Rice NE, Lewis C, Henley WE, Galloway TS (2010) Association of urinary bisphenol A concentration with heart disease: evidence from NHANES 2003/06. PLoS ONE 5:e8673

    Article  Google Scholar 

  • Melzer D, Osborne NJ, Henley WE, Cipelli R, Young A, Money C, McCormack P, Luben R, Khaw KT, Wareham NJ, Galloway TS (2012) Urinary bisphenol A concentration and risk of future coronary artery disease in apparently healthy men and women. Circulation 125:1482–1490

    Article  CAS  Google Scholar 

  • Miller FJJ, Gutterman DD, Rios CD, Heistad DD, Davidson BL (1998) Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis. Circ Res 82:1298–1305

    Article  CAS  Google Scholar 

  • Miyawaki J, Sakayama K, Kato H, Yamamoto H, Masuno H (2007) Perinatal and postnatal exposure to bisphenol a increases adipose tissue mass and serum cholesterol level in mice. J Atheroscler Thromb 14:245–252

    Article  CAS  Google Scholar 

  • Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142

    CAS  Google Scholar 

  • Moshage H, Kok B, Huizenga JR (1995) Nitrite and nitrate determination in plasma: a critical evaluation. Clin Chem 41:892–896

    CAS  Google Scholar 

  • Mourad IM, Khadrawy YA (2012) The sensitivity of liver, kidney and testis of rats to oxidative stress induced by different doses of bisphenol A. Int J Life Sci Pharma Res 2:L19–L28

    Article  Google Scholar 

  • Newbold RR, Padilla-Banks E, Jefferson WN (2009) Environmental estrogens and obesity. Mol Cell Endocrinol 304:84–89

    Article  CAS  Google Scholar 

  • Olsén L, Lind L, Lind PM (2012) Associations between circulating levels of bisphenol A and phthalate metabolites and coronary risk in the elderly. Ecotoxicol Environ Saf 80:179–183

    Article  Google Scholar 

  • Pant J, Ranjan P, Deshpande SB (2011) Bisphenol A decreases atrial contractility involving NO-dependent G-cyclase signaling pathway. J Appl Toxicol 31:698–702

    Article  CAS  Google Scholar 

  • Pastorea A, Federicia G, Bertini E, Piemonte F (2003) Analysis of glutathione: implication in redox and detoxification. Clin Chim Acta 333:19–39

    Article  Google Scholar 

  • Patel BB, Raad M, Sebag IA, Chalifour LE (2013) Lifelong exposure to bisphenol a alters cardiac structure/function, protein expression, and DNA methylation in adult mice. Toxicol Sci 133:174–185

    Article  CAS  Google Scholar 

  • Petros A, Bennett D, Vallance P (1991) Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet 338:1557–1558

    Article  CAS  Google Scholar 

  • Pigeolet E, Corbisier P, Houbion A, Lambert D, Michiels DC, Raes M, Zachary D, Ramacle J (1990) Glutathione peroxidase, superoxide dismutase and catalase inactivation by peroxides and oxygen derived free radicals. Mech Ageing Dev 51:283–290

    Article  CAS  Google Scholar 

  • Reilly JJ (2005) Descriptive epidemiology and health consequences of childhood obesity. Best Pract Res Clin Endocrinol Metab 19:327–341

    Article  Google Scholar 

  • Richter CA, Birnabaum LS, Farabollini F, Newbold RR, Rubin BS, Talsness CE, Vaderbergh JC, Walser-Kuntz DR, vom Saal FS (2007) In vivo effect of bisphenol A in laboratory rodent studies. Reprod Toxicol 24:199–224

    Google Scholar 

  • Ritter S (2011) Debating BPA’s toxicity. Chem Eng News 89:5–13

    Google Scholar 

  • Ropero AB, Alonso-Magdalena P, Garcia–Garcia E, Ripoll C, Fuentes E, Nadal A (2008) Bisphenol-A disruption of the endocrine pancreas and blood glucose homeostasis. Int J Androl 31:194–200

    Article  CAS  Google Scholar 

  • Roy P, Venkat RG, Naidu MUR, Usha RP (2005) Recent trends in the nitrergic nervous system. Educational Forum 37:69–76

    CAS  Google Scholar 

  • Rubin BS, Soto AM (2009) Bisphenol A: perinatal exposure and body weight. Mol Cell Endocrinol 304:55–62

    Article  CAS  Google Scholar 

  • Rubin BS, Murray MK, Damassa DA, King JC, Soto AM (2001) Perinatal exposure to low doses of bisphenol-A affects body weight, patterns of estrous cyclicity and plasma LH levels. Environ Health Perspect 109:675–680

    Article  CAS  Google Scholar 

  • Ruiz-Larrea MB, Leal AM, Liza M (1994) Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids 59:383–388

    Article  CAS  Google Scholar 

  • Scherrer-Crosbie M, Ullrich R, Bloch KD, Nakajima H, Nasseri B, Aretz HT, Lindsey ML, Vançon AC, Huang PL, Lee RT, Zapol WM, Picard MH (2001) Endothelial nitric oxide synthase limits left ventricular remodeling after myocardial infarction in mice. Circulation 104:1286–1291

    Article  CAS  Google Scholar 

  • Shah AM, Vallance P, Harrison D (1999) NO in the cardiovascular system. Cardiovasc Res 43:507–508

    Article  CAS  Google Scholar 

  • Shankar A, Teppala S, Sabanayagam C (2012) Urinary bisphenol-A levels and measures of obesity: results from the National Health and Nutrition Examination Survey 2003–2008. ISRN Endocrinol 2012:965243. doi:10.5402/2012/965243

  • Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoy-Agid F, Jenner P, Marsden CD (1994) Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting the basal ganglia. Annals Neurol 36:348–355

    Article  CAS  Google Scholar 

  • Sugamura K, Keaney JF (2011) Reactive oxygen species in cardiovascular disease. Free Radic Biol Med 51:978–992

    Article  CAS  Google Scholar 

  • Trasande L, Attina TM, Blustein J (2012) Association between urinary bisphenol A concentration and obesity prevalence in children and adolescents. JAMA 308:1113–1121

    Article  CAS  Google Scholar 

  • Tribulová N, Okruhlicová L, Bernátová I, Pechánová O (2000) Chronic disturbances in NO production results in histochemical and subcellular alterations of the rat heart. Physiol Res 49:77–88

    Google Scholar 

  • Tsakiris S, Angelogianni P, Schulpis KH, Stavridis JC (2000) Protective effect of l-phenylalanine on rat brain acetylcholinesterase inhibition induced by free radicals. Clin Biochem 33:103–106

    Article  CAS  Google Scholar 

  • Tsutsui H, Kinugawa S, Matsushima S (2009) Mitochondrial oxidative stress and dysfunction in myocardial remodeling. Cardiovas Res 81:449–456

    Article  CAS  Google Scholar 

  • Vandenberg LN, Maffini MV, Sonnenschein C, Rubin BS, Soto AM (2009) Bisphenol-a and the great divide: a review of controversies in the field of endocrine disruption. Endocrine Rev 30 :75–95

    Google Scholar 

  • Vandenberg LN, Wadia PR, Schaeberle CM, Rubin BS, Sonnenschein C, Soto AM (2006) The mammary gland response to estradiol: monotonic at the cellular level, non-monotonic at the tissue-level of organization? J Steroid Biochem Molec Biol 101:263–274

    Google Scholar 

  • Vaziri ND, Wang XQ, Oveisi F, Rad B (2000) Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. Hypertension 36:142–146

    Article  CAS  Google Scholar 

  • vom Saal FS (2006) Bisphenol A references: list of published articles. http://endocrinedisruptors.missouri.edu/vomsaal/vomsaal.html

  • vom Saal FS, Hughes C (2005) An extensive new literature concerning low dose effects of bisphenol A shows the need for a new risk assessment. Environ Health Perspect 113:926–933

    Article  Google Scholar 

  • vom Saal FS, Myers JP (2008) Bisphenol A and risk of metabolic disorders. JAMA 300:1353–1355

    Article  Google Scholar 

  • Wade GN, Schneider JE (1992) Metabolic fuels and reproduction in female mammals. Neurosci Biobehav Rev 16:235–272

    Article  CAS  Google Scholar 

  • Welshons WV, Thayer KA, Judy BM, Taylor JA, Curran EM, vom Saal FS (2003) Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity. Environ Health Perspect 111:994–1006

    Article  CAS  Google Scholar 

  • Wyse AT, Stefanello FM, Chiarani F, Delwing D, Wannmacher CM, Wajner M (2004) Arginine administration decreases cerebral cortex acetylcholinesterase and serum butyrylcholinesterase probably by oxidative stress induction. Neurochem Res 29:385–389

    Article  CAS  Google Scholar 

  • Ye XB, Pierik FH, Hauser R, Duty S, Angerer J, Park MM, Burdorf A, Hofman A, Jaddoe VWV, Mackenbach JP, Steegers EAP, Tiemeier H, Longnecker MP (2008) Urinary metabolite concentrations of organophosphorous pesticides, bisphenol A, and phthalates among pregnant women in Rotterdam, the Netherlands: the Generation R study. Environ Res 108:260–267

    Article  CAS  Google Scholar 

  • Zweier JL, Rayburn BK, Flaherty JT, Weisfeldt ML (1987) Recombinant superoxide dismutase reduces oxygen free radical concentrations in reperfused myocardium. J Clin Invest 80:1728–1734

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Zoology Department, Faculty of Science, Cairo University, Giza, Egypt

    Heba S. Aboul Ezz & Iman M. Mourad

  2. Medical Physiology Department, Medical Division, National Research Center, Giza, Egypt

    Yasser A. Khadrawy

Authors
  1. Heba S. Aboul Ezz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasser A. Khadrawy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Iman M. Mourad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heba S. Aboul Ezz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aboul Ezz, H.S., Khadrawy, Y.A. & Mourad, I.M. The effect of bisphenol A on some oxidative stress parameters and acetylcholinesterase activity in the heart of male albino rats. Cytotechnology 67, 145–155 (2015). https://doi.org/10.1007/s10616-013-9672-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10616-013-9672-1

Keywords

Search

Navigation