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Endocrine, Metabolic & Immune Disorders - Drug Targets


ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Melatonin Ameliorates BPA Induced Oxidative Stress in Human Red Blood Cells: An In vitro Study

Author(s): Saleh M. Abdullah* and Hina Rashid

Volume 20, Issue 8, 2020

Page: [1321 - 1327] Pages: 7

DOI: 10.2174/1871530320666200505112023

Price: $65


Background: Bisphenol A (BPA) is a xenobiotic that causes oxidative stress in various organs in living organisms. Blood cells are also an endpoint where BPA is known to cause oxidative stress. Blood cells, especially red blood cells (RBCs), are crucial for maintaining homeostasis and overall wellbeing of the organism. They are highly susceptible to oxidative stress induced by xenobiotics. However, there is limited data about the oxidative stress induced by BPA in blood, especially in red blood cells. This study was carried out to evaluate BPA induced oxidative stress in human RBCs in vitro and its amelioration by melatonin.

Objective: To find if melatonin exerts a protective effect on the oxidative stress induced by the BPA in human red blood cells in vitro.

Methods: The erythrocyte suspensions (2 ml) were divided into six groups and treated with 0, 50, 100, 150, 200, and 250 μg/ml of BPA. Another set of erythrocyte suspension with similar BPA treatment and 50 μM Melatonin per group was also set. Incubations lasted for 12 hrs in the dark. Lipid peroxidation, glutathione, glutathione reductase, catalase, and superoxide dismutase were measured as indicators of oxidative stress.

Results: BPA caused a significant increase in lipid peroxidation. A decrease in GSH levels was also observed. The activities of all the studied antioxidants also decreased with BPA treatment. Melatonin was seen to mitigate the oxidative stress induced by BPA.

Conclusion: Treatment of red blood cells with BPA caused an increase in oxidative stress, while melatonin decreased the induced oxidative stress.

Keywords: Bisphenol A, xenobiotic, red blood cells, oxidative stress, melatonin, in vitro.

Graphical Abstract
Naughton, S.X.; Terry, A.V., Jr Neurotoxicity in acute and repeated organophosphate exposure. Toxicology, 2018, 408, 101-112.
[] [PMID: 30144465]
Jandegian, C.M.; Deem, S.L.; Bhandari, R.K.; Holliday, C.M.; Nicks, D.; Rosenfeld, C.S.; Selcer, K.W.; Tillitt, D.E.; Vom Saal, F.S.; Vélez-Rivera, V.; Yang, Y.; Holliday, D.K. Developmental exposure to bisphenol A (BPA) alters sexual differentiation in painted turtles (Chrysemys picta). Gen. Comp. Endocrinol., 2015, 216, 77-85.
[] [PMID: 25863134]
Geens, T.; Aerts, D.; Berthot, C.; Bourguignon, J.P.; Goeyens, L.; Lecomte, P.; Maghuin-Rogister, G.; Pironnet, A.M.; Pussemier, L.; Scippo, M.L.; Van Loco, J.; Covaci, A. A review of dietary and non-dietary exposure to bisphenol-A. Food Chem. Toxicol., 2012, 50(10), 3725-3740.
[] [PMID: 22889897]
Konieczna, A.; Rutkowska, A.; Rachoń, D. Health risk of exposure to Bisphenol A (BPA). Rocz. Panstw. Zakl. Hig., 2015, 66(1), 5-11.
[PMID: 25813067]
Liu, Y.; Qu, K.; Hai, Y.; Zhao, C.; Bisphenol, A.; Bisphenol, A. BPA) binding on full-length architectures of estrogen receptor. J. Cell. Biochem., 2018, 119(8), 6784-6794.
[] [PMID: 29737547]
Rashid, H.; Ahmad, F.; Rahman, S.; Ansari, R.A.; Bhatia, K.; Kaur, M.; Islam, F.; Raisuddin, S. Iron deficiency augments bisphenol A-induced oxidative stress in rats. Toxicology, 2009, 256(1-2), 7-12.
[] [PMID: 19041362]
Elswefy, S.E.; Abdallah, F.R.; Atteia, H.H.; Wahba, A.S.; Hasan, R.A. Inflammation, oxidative stress and apoptosis cascade implications in bisphenol A-induced liver fibrosis in male rats. Int. J. Exp. Pathol., 2016, 97(5), 369-379.
[] [PMID: 27925325]
Khodayar, M.J.; Kalantari, H.; Mahdavinia, M.; Khorsandi, L.; Alboghobeish, S.; Samimi, A.; Alizadeh, S.; Zeidooni, L. Protective effect of naringin against BPA-induced cardiotoxicity through prevention of oxidative stress in male Wistar rats. Drug Chem. Toxicol., 2018, 28, 1-11.
[] [PMID: 30264589]
Tiwari, D.; Vanage, G.; Bisphenol, A.; Bisphenol, A. Induces Oxidative Stress in Bone Marrow Cells, Lymphocytes, and Reproductive Organs of Holtzman Rats. Int. J. Toxicol., 2017, 36(2), 142-152.
[] [PMID: 28403740]
Kaur, S.; Saluja, M.; Bansal, M.P. Bisphenol A induced oxidative stress and apoptosis in mice testes: Modulation by selenium. Andrologia, 2018, 50(3), 3.
[] [PMID: 28719015]
Kaur, K.; Chauhan, V.; Gu, F.; Chauhan, A. Bisphenol A induces oxidative stress and mitochondrial dysfunction in lymphoblasts from children with autism and unaffected siblings. Free Radic. Biol. Med., 2014, 76, 25-33.
[] [PMID: 25101517]
Watkins, D.J.; Ferguson, K.K. Anzalota, Del Toro, L.V.; Alshawabkeh, A.N.; Cordero, J.F.; Meeker, J.D. Associations between urinary phenol and paraben concentrations andmarkers of oxidative stress and inflammation among pregnant women in Puerto Rico. Int. J. Hyg. Environ. Health, 2015, 218(2), 212-219.
[] [PMID: 25435060]
Han, C.; Hong, Y.C. Bisphenol A, hypertension, and cardiovascular diseases: epidemiological, laboratory, and clinical trial evidence. Curr. Hypertens. Rep., 2016, 18(2), 11.
[] [PMID: 26781251]
Piao, X.; Liu, Z.; Li, Y.; Yao, D.; Sun, L.; Wang, B.; Ma, Y.; Wang, L.; Zhang, Y. Investigation of the effect for bisphenol A on oxidative stress in human hepatocytes and its interaction with catalase. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2019, 221117149
[]] [PMID: 31153119]
Anderson, H.L.; Brodsky, I.E.; Mangalmurti, N.S. The Evolving Erythrocyte: Red blood cells as modulators of innate immunity. J. Immunol., 2018, 201(5), 1343-1351.
[] [PMID: 30127064]
Buttari, B.; Profumo, E.; Riganò, R. Crosstalk between red blood cells and the immune system and its impact on atherosclerosis. BioMed Res. Int., 2015, 2015616834
[PMID: 25722984] []]
Toker, S.; Rogowski, O.; Melamed, S.; Shirom, A.; Shapira, I.; Berliner, S.; Zeltser, D. Association of components of the metabolic syndrome with the appearance of aggregated red blood cells in the peripheral blood. An unfavorable hemorheological finding. Diabetes Metab. Res. Rev., 2005, 21(2), 197-202.
[] [PMID: 15386807]
Han, X.; Wang, C.; Liu, Z. Red blood cells as smart delivery systems. Bioconjug. Chem., 2018, 29(4), 852-860.
[] [PMID: 29298380]
Venter, C.; Oberholzer, H.M.; Bester, J.; van Rooy, M.J.; Bester, M.J. Ultrastructural, confocal and viscoelastic characteristics of whole blood and plasma after exposure to cadmium and chromium alone and in combination: An ex vivo study. Cell. Physiol. Biochem., 2017, 43(3), 1288-1300.
[] [PMID: 28992628]
Mohanty, J.G.; Nagababu, E.; Rifkind, JM. Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging., Front. Physiol, 2014, 28, 5, 84..
Pandey, K.B.; Rizvi, S.I. Resveratrol may protect plasma proteins from oxidation under conditions of oxidative stress in vitro. J. Braz. Chem. Soc., 2010, 21, 909-913.
de Oliveira, S.; Saldanha, C. An overview about erythrocyte membrane. Clin. Hemorheol. Microcirc., 2010, 44(1), 63-74.
[] [PMID: 20134094]
Maćczak, A.; Cyrkler, M.; Bukowska, B.; Michałowicz, J. Bisphenol A, bisphenol S, bisphenol F and bisphenol AF induce different oxidative stress and damage in human red blood cells (in vitro study). Toxicol. In Vitro, 2017, 41, 143-149.
[] [PMID: 28259788]
Sangai, N.P.; Patel, C.N.; Pandya, H.A. Ameliorative effects of quercetin against bisphenol A-caused oxidative stress in human erythrocytes: an in vitro and in silico study. Toxicol. Res. (Camb.), 2018, 7(6), 1091-1099.
[] [PMID: 30542603]
Zhang, H.M.; Zhang, Y. Melatonin: A well-documented antioxidant with conditional pro-oxidant actions J. Pineal. Res, 2014, 57, 131.146..
El-Missiry, M.A.; Othman, A.I.; Al-Abdan, M.A.; El-Sayed, A.A. Melatonin ameliorates oxidative stress, modulates death receptor pathway proteins, and protects the rat cerebrum against bisphenol-A-induced apoptosis. J. Neurol. Sci., 2014, 347(1-2), 251-256.
[] [PMID: 25454643]
Tesoriere, L.; D’Arpa, D.; Conti, S.; Giaccone, V.; Pintaudi, A.M.; Livrea, M.A. Melatonin protects human red blood cells from oxidative hemolysis: New insights into the radical-scavenging activity. J. Pineal Res., 1999, 27(2), 95-105.
[] [PMID: 10496145]
Koc, M.; Buyukokuroglu, M.E.; Taysi, S. The effect of melatonin on peripheral blood cells during total body irradiation in rats. Biol. Pharm. Bull., 2002, 25(5), 656-657.
[] [PMID: 12033509]
Lee, F.Y.; Sun, C.K.; Sung, P.H.; Chen, K.H.; Chua, S.; Sheu, J.J.; Chung, S.Y.; Chai, H.T.; Chen, Y.L.; Huang, T.H.; Huang, C.R.; Li, Y.C.; Luo, C.W.; Yip, H.K. Daily melatonin protects the endothelial lineage and functional integrity against the aging process, oxidative stress, and toxic environment and restores blood flow in critical limb ischemia area in mice. J. Pineal Res., 2018, 65(2)e12489
[] [PMID: 29570854]
Suthar, H.; Verma, R.J.; Patel, S.; Jasrai, Y.T. Green tea potentially ameliorates bisphenol a-induced oxidative stress: an in vitro and in silico study. Biochem. Res. Int., 2014, 2014259763
[]] [PMID: 25180096]
Stocks, J.; Dormandy, T.L. The autoxidation of human red cell lipids induced by hydrogen peroxide. Br. J. Haematol., 1971, 20(1), 95-111.
[] [PMID: 5540044]
Beutler, E. Glutathione reductase: stimulation in normal subjects by riboflavin supplementation. Science, 1969, 165(3893), 613-615.
[] [PMID: 5794396]
Paglia, D.E.; Valentine, W.N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med., 1967, 70(1), 158-169.
[PMID: 6066618]
Mohandas, J.; Marshall, J.J.; Duggins, G.G.; Horvath, J.S.; Tiller, D. Differential distribution of glutathione and glutathione related enzymes in rabbit kidney: possible implications in analgesic neuropathy. Cancer Res., 1984, 44, 5086-5091.
[PMID: 6149017]
Claiborne, A. Catalase activity.1985, 1985., 283.284..
Sun, Y.; Oberley, L.W.; Li, Y. A simple method for clinical assay of superoxide dismutase. Clin. Chem., 1988, 34(3), 497-500.
[] [PMID: 3349599]
Pizzorno, J. Conventional laboratory tests to assess toxin burden. Integr. Med. (Encinitas), 2015, 14(5), 8-16.
[PMID: 26770160]
Maćczak, A.; Cyrkler, M.; Bukowska, B.; Michałowicz, J. Eryptosis-inducing activity of bisphenol A and its analogs in human red blood cells (in vitro study). J. Hazard. Mater., 2016, 307, 328-335.
[] [PMID: 26799224]
Olchowik-Grabarek, E.; Makarova, K.; Mavlyanov, S.; Abdullajanova, N.; Zamaraeva, M. Comparative analysis of BPA and HQ toxic impacts on human erythrocytes, protective effect mechanism of tannins (Rhus typhina). Environ. Sci. Pollut. Res. Int., 2018, 25(2), 1200-1209.
[] [PMID: 29082470]
Pandey, K.B.; Rizvi, S.I. Biomarkers of oxidative stress in red blood cells. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., 2011, 155(2), 131-136.
[] [PMID: 21804621]
Lim, H.Y.; Ho, Q.S.; Wong, K.P. Interplay of metabolizing enzymes and transporter of xenobiotics. Xenobiotica, 2016, 46(1), 25-33.
[PMID: 26226519]
Bryszewska, M.; Zavodnik, I.B.; Niekurzak, A.; Szosland, K. Oxidative processes in red blood cells from normal and diabetic individuals. Biochem. Mol. Biol. Int., 1995, 37(2), 345-354.
[PMID: 8673018]
Limón-Pacheco, J.; Gonsebatt, M.E. The role of antioxidants and antioxidant-related enzymes in protective responses to environmentally induced oxidative stress. Mutat. Res., 2009, 674(1-2), 137-147.
[] [PMID: 18955158]
Pieri, C.; Marra, M.; Moroni, F.; Recchioni, R.; Marcheselli, F. Melatonin: A peroxyl radical scavenger more effective than vitamin E. Life Sci., 1994, 55(15), PL271-PL276.
[] [PMID: 7934611]
Pertsov, S.S.; Kalinichenko, L.S.; Koplik, E.V.; Nagler, L.G.; Alinkina, E.S.; Kozachenko, A.I. Effect of melatonin on antioxidant enzyme activities in blood erythrocytes of rats during acute emotional stress. Biomed. Khim., 2015, 3, 394-399.
[] [PMID: 26215419]
Galley, H.F.; Lowes, D.A.; Allen, L.; Cameron, G.; Aucott, L.S.; Webster, N.R. Melatonin as a potential therapy for sepsis: A phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis. J. Pineal Res., 2014, 56(4), 427-438.
[] [PMID: 24650045]

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