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Neurotoxic effects of bisphenol A on SH-SY5Y neuroblastoma cells via nitric oxide

Yıl 2019, Cilt: 23 Sayı: 3, 354 - 359, 27.06.2025

Beyza Ayazgök Zekiye Tuba Tüylü Küçükkılınç

Öz

Bisphenol A (BPA, 2,2-bis(4-hydroxyphenyl)propane)polycarbonate is an industrial component frequently used as an additive in the construction of epoxy resin and other non-polymer plastics. In this study cytotoxicity of low dose BPA (0.01 μM-100 μM ) and NO levels in SH-SY5Y cells were assessed together to determine whether there is a correlation between of them. MTT Cytotoxicity assays were performed by applying BPA at increasing doses (0.01 μM-100 μM) for 8, 24, 72 hours. Measurements to determine the nitric oxide (NO) levels of the cells, were made using the Griess method at the same time intervals and at the equal doses with BPA. It is found that percentage viability values in SH-SY5Y cells treated with 100 µM BPA for 8 hours, is reduced statistically significant compared to control groups (p<0.001). A significant correlation was found between cytotoxicity results and NO levels of cells treated BPA (0.01 μM-100 μM) for 8 and 72 hours ( p<0.01, p<0.001 respectively). Neurotoxic effects of low dose BPA exposure on SH-SY5Y cells may be explained with increase in the levels of NO as a result from different parameters. One of these parameters could be a disorder in the synthesis of nNOS on different stages such as transcription and translation.

Anahtar Kelimeler

Bisphenol A nitric oxide cytotoxicity neurotoxicity.

Kaynakça

  • [1] Wetherill YB, Akingbemi BT, Kanno J, McLachlan JA, Nadal A, Sonnenschein C, Watson CS, Zoeller RT, Belcher SM. In vitro molecular mechanisms of bisphenol A action. Reprod Toxicol. 2007; 24(2): 178-198. [CrossRef]
  • [2] Geens T, Aerts D, Berthot C, Bourguignon JP, Goeyens L, Lecomte P, Maghuin-Rogister G, Pironnet AM, Pussemier L, Scippo ML, Van Loco J, Covaci A. A review of dietary and non-dietary exposure to bisphenol-A. Food Chem Toxicol. 2012; 50(10): 3725-3740. [CrossRef]
  • [3] Negri-Cesi P. Bisphenol A Interaction with brain development and functions. Dose Response. 2015; 13(2): 1559325815590394. [CrossRef]
  • [4] Zhou Y, Wang Z, Xia M, Zhuang S, Gong X, Pan J, Li C, Fan R, Pang Q, Lu S. Neurotoxicity of low bisphenol A (BPA) exposure for young male mice: Implications for children exposed to environmental levels of BPA. Environ Pollut. 2017; 229: 40-48. [CrossRef]
  • [5] Doerge DR, Vanlandingham M, Nathan C, Twaddle K, Delclos B. Lactational transfer of bisphenol A in Sprague Dawley rats. Toxicol Lett. 2010; 199(3): 372-376. [CrossRef]
  • [6] Andrew PJ, Mayer B. Enzymatic function of nitric oxide synthases. Cardiovasc Res. 1999; 43(3): 521-531. [CrossRef]
  • [7] Kopincová J, Púzserová A, Bernátová I. Biochemical aspects of nitric oxide synthase feedback regulation by nitric oxide. Interdiscip Toxicol. 2011; 4(2): 63-68. [CrossRef]
  • [8] Szymanska K, Calka J, Gonkowski S. Nitric oxide as an active substance in the enteric neurons of the porcine digestive tract in physiological conditions and under intoxication with bisphenol A (BPA). Nitric Oxide. 2018; 80: 1-11. [CrossRef]
  • [9] Itoh K, Yaoi T, Fushiki S. Bisphenol A, an endocrine-disrupting chemical, and brain development. Neuropathology. 2012; 32(4): 447-457. [CrossRef]
  • [10] Prast H, Tran MH, Fischer H, Philippu A. Nitric oxide-induced release of acetylcholine in the nucleus accumbens: role of cyclic GMP, glutamate, and GABA. J Neurochem. 1998; 71(1): 266-273. [CrossRef]
  • [11] Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Allan Butterfield D, Giuffrida Stella AM. Nitric oxide in the central nervous system: Neuroprotection versus neurotoxicity. Nat Rev Neurosci. 2007; 8(10): 766-775. [CrossRef]
  • [12] Lipton SA. Neuronal protection and destruction by NO. Cell Death Differ. 1999; 6: 943. [CrossRef]
  • [13] Kröncke KD, Fehsel K, Kolb-Bachofen V. Nitric Oxide: Cytotoxicity versus cytoprotection—How, why, when, and where? Nitric Oxide. 1997; 1(2): 107-120. [CrossRef]
  • [14] Schulz JB, Matthews RT, Beal MF. Role of nitric oxide in neurodegenerative diseases. Curr Opin Neurol. 1995; 8(6): 480-486.
  • [15] Brune B, Knethen A, Sandau KB. Nitric oxide (NO): an effector of apoptosis. Cell Death Differ. 1999; 6(10): 969-975. [CrossRef]
  • [16] Dhakshinamoorthy S, Sridharan SR, Li L, Ng PY, Boxer LM, Porter AG. Protein/DNA arrays identify nitric oxide regulated cis-element and trans-factor activities some of which govern neuroblastoma cell viability. Nucleic Acids Res. 2007; 35(16): 5439-5451. [CrossRef]
  • [17] Li L, Feng Z, Porter AG. JNK-dependent phosphorylation of c-Jun on serine 63 mediates nitric oxide-induced apoptosis of neuroblastoma cells. J Biol Chem. 2004; 279(6): 4058-4065. [CrossRef]
  • [18] Ayazgök B, Küçükkılınç T. Low-dose bisphenol A induces RIPK1-mediated necroptosis in SH-SY5Y cells: Effects on TNF-α and acetylcholinesterase. J Biochem Mol Toxicol. 2018; 33(1): e22233. [CrossRef]
  • [19] Kurt O, Özdal-Kurt, Akçora CM, Özkut M, Tuğlu MI. Neurotoxic, cytotoxic, apoptotic and antiproliferative effects of some marine algae extracts on the NA2B cell line. Biotech Histochem. 2018; 93(1): 59-69. [CrossRef]
  • [20] Ghatan S, Larner S, Kinoshita Y, Hetman M, Patel L, Xia Z, Youle RJ, Morrison RS. p38 MAP kinase mediates bax translocation in nitric oxide-induced apoptosis in neurons. J Cell Biol. 2000; 150(2): 335-347.

Yıl 2019, Cilt: 23 Sayı: 3, 354 - 359, 27.06.2025

Beyza Ayazgök Zekiye Tuba Tüylü Küçükkılınç

Öz

Kaynakça

  • [1] Wetherill YB, Akingbemi BT, Kanno J, McLachlan JA, Nadal A, Sonnenschein C, Watson CS, Zoeller RT, Belcher SM. In vitro molecular mechanisms of bisphenol A action. Reprod Toxicol. 2007; 24(2): 178-198. [CrossRef]
  • [2] Geens T, Aerts D, Berthot C, Bourguignon JP, Goeyens L, Lecomte P, Maghuin-Rogister G, Pironnet AM, Pussemier L, Scippo ML, Van Loco J, Covaci A. A review of dietary and non-dietary exposure to bisphenol-A. Food Chem Toxicol. 2012; 50(10): 3725-3740. [CrossRef]
  • [3] Negri-Cesi P. Bisphenol A Interaction with brain development and functions. Dose Response. 2015; 13(2): 1559325815590394. [CrossRef]
  • [4] Zhou Y, Wang Z, Xia M, Zhuang S, Gong X, Pan J, Li C, Fan R, Pang Q, Lu S. Neurotoxicity of low bisphenol A (BPA) exposure for young male mice: Implications for children exposed to environmental levels of BPA. Environ Pollut. 2017; 229: 40-48. [CrossRef]
  • [5] Doerge DR, Vanlandingham M, Nathan C, Twaddle K, Delclos B. Lactational transfer of bisphenol A in Sprague Dawley rats. Toxicol Lett. 2010; 199(3): 372-376. [CrossRef]
  • [6] Andrew PJ, Mayer B. Enzymatic function of nitric oxide synthases. Cardiovasc Res. 1999; 43(3): 521-531. [CrossRef]
  • [7] Kopincová J, Púzserová A, Bernátová I. Biochemical aspects of nitric oxide synthase feedback regulation by nitric oxide. Interdiscip Toxicol. 2011; 4(2): 63-68. [CrossRef]
  • [8] Szymanska K, Calka J, Gonkowski S. Nitric oxide as an active substance in the enteric neurons of the porcine digestive tract in physiological conditions and under intoxication with bisphenol A (BPA). Nitric Oxide. 2018; 80: 1-11. [CrossRef]
  • [9] Itoh K, Yaoi T, Fushiki S. Bisphenol A, an endocrine-disrupting chemical, and brain development. Neuropathology. 2012; 32(4): 447-457. [CrossRef]
  • [10] Prast H, Tran MH, Fischer H, Philippu A. Nitric oxide-induced release of acetylcholine in the nucleus accumbens: role of cyclic GMP, glutamate, and GABA. J Neurochem. 1998; 71(1): 266-273. [CrossRef]
  • [11] Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Allan Butterfield D, Giuffrida Stella AM. Nitric oxide in the central nervous system: Neuroprotection versus neurotoxicity. Nat Rev Neurosci. 2007; 8(10): 766-775. [CrossRef]
  • [12] Lipton SA. Neuronal protection and destruction by NO. Cell Death Differ. 1999; 6: 943. [CrossRef]
  • [13] Kröncke KD, Fehsel K, Kolb-Bachofen V. Nitric Oxide: Cytotoxicity versus cytoprotection—How, why, when, and where? Nitric Oxide. 1997; 1(2): 107-120. [CrossRef]
  • [14] Schulz JB, Matthews RT, Beal MF. Role of nitric oxide in neurodegenerative diseases. Curr Opin Neurol. 1995; 8(6): 480-486.
  • [15] Brune B, Knethen A, Sandau KB. Nitric oxide (NO): an effector of apoptosis. Cell Death Differ. 1999; 6(10): 969-975. [CrossRef]
  • [16] Dhakshinamoorthy S, Sridharan SR, Li L, Ng PY, Boxer LM, Porter AG. Protein/DNA arrays identify nitric oxide regulated cis-element and trans-factor activities some of which govern neuroblastoma cell viability. Nucleic Acids Res. 2007; 35(16): 5439-5451. [CrossRef]
  • [17] Li L, Feng Z, Porter AG. JNK-dependent phosphorylation of c-Jun on serine 63 mediates nitric oxide-induced apoptosis of neuroblastoma cells. J Biol Chem. 2004; 279(6): 4058-4065. [CrossRef]
  • [18] Ayazgök B, Küçükkılınç T. Low-dose bisphenol A induces RIPK1-mediated necroptosis in SH-SY5Y cells: Effects on TNF-α and acetylcholinesterase. J Biochem Mol Toxicol. 2018; 33(1): e22233. [CrossRef]
  • [19] Kurt O, Özdal-Kurt, Akçora CM, Özkut M, Tuğlu MI. Neurotoxic, cytotoxic, apoptotic and antiproliferative effects of some marine algae extracts on the NA2B cell line. Biotech Histochem. 2018; 93(1): 59-69. [CrossRef]
  • [20] Ghatan S, Larner S, Kinoshita Y, Hetman M, Patel L, Xia Z, Youle RJ, Morrison RS. p38 MAP kinase mediates bax translocation in nitric oxide-induced apoptosis in neurons. J Cell Biol. 2000; 150(2): 335-347.
Toplam 20 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık Biyokimyası
Bölüm Articles
Yazarlar

Beyza Ayazgök

Zekiye Tuba Tüylü Küçükkılınç

Yayımlanma Tarihi 27 Haziran 2025
Yayımlandığı Sayı Yıl 2019 Cilt: 23 Sayı: 3

Kaynak Göster

APA Ayazgök, B., & Tüylü Küçükkılınç, Z. T. (2025). Neurotoxic effects of bisphenol A on SH-SY5Y neuroblastoma cells via nitric oxide. Journal of Research in Pharmacy, 23(3), 354-359.
AMA Ayazgök B, Tüylü Küçükkılınç ZT. Neurotoxic effects of bisphenol A on SH-SY5Y neuroblastoma cells via nitric oxide. J. Res. Pharm. Haziran 2025;23(3):354-359.
Chicago Ayazgök, Beyza, ve Zekiye Tuba Tüylü Küçükkılınç. “Neurotoxic Effects of Bisphenol A on SH-SY5Y Neuroblastoma Cells via Nitric Oxide”. Journal of Research in Pharmacy 23, sy. 3 (Haziran 2025): 354-59.
EndNote Ayazgök B, Tüylü Küçükkılınç ZT (01 Haziran 2025) Neurotoxic effects of bisphenol A on SH-SY5Y neuroblastoma cells via nitric oxide. Journal of Research in Pharmacy 23 3 354–359.
IEEE B. Ayazgök ve Z. T. Tüylü Küçükkılınç, “Neurotoxic effects of bisphenol A on SH-SY5Y neuroblastoma cells via nitric oxide”, J. Res. Pharm., c. 23, sy. 3, ss. 354–359, 2025.
ISNAD Ayazgök, Beyza - Tüylü Küçükkılınç, Zekiye Tuba. “Neurotoxic Effects of Bisphenol A on SH-SY5Y Neuroblastoma Cells via Nitric Oxide”. Journal of Research in Pharmacy 23/3 (Haziran 2025), 354-359.
JAMA Ayazgök B, Tüylü Küçükkılınç ZT. Neurotoxic effects of bisphenol A on SH-SY5Y neuroblastoma cells via nitric oxide. J. Res. Pharm. 2025;23:354–359.
MLA Ayazgök, Beyza ve Zekiye Tuba Tüylü Küçükkılınç. “Neurotoxic Effects of Bisphenol A on SH-SY5Y Neuroblastoma Cells via Nitric Oxide”. Journal of Research in Pharmacy, c. 23, sy. 3, 2025, ss. 354-9.
Vancouver Ayazgök B, Tüylü Küçükkılınç ZT. Neurotoxic effects of bisphenol A on SH-SY5Y neuroblastoma cells via nitric oxide. J. Res. Pharm. 2025;23(3):354-9.