Cytotoxicity induced by cypermethrin in Human Neuroblastoma Cell Line SH-SY5Y
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Department of Physiopathology, Institute of Rural Health, Lublin, Poland
Department of Medical Biology, Institute of Rural Health, Lublin, Poland
Corresponding author
Grzegorz Raszewski   

Department of Physiopathology, Institute of Rural Health, Lublin, Poland
Ann Agric Environ Med. 2016;23(1):106-110
The purpose of this study was to evaluate the cytotoxic potential of Cypermethrin (CM) on cultured human Neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with CM at 0–200µM for 24, 48, and 72 h, in vitro. It was found that CM induced the cell death of Neuroblastoma cells in a dose- and time-dependent manner, as shown by LDH assays. Next, some aspects of the process of cell death triggered by CM in the human SH-SY5Y cell line were investigated. It was revealed that the pan-caspase inhibitor Q-VD-OPh, sensitizes SH-SY5Y cells to necroptosis caused by CM. Furthermore, signal transduction inhibitors PD98059, SL-327, SB202190, SP600125 failed to attenuate the effect of the pesticide. Finally, it was shown that inhibition of TNF-a by Pomalidomide (PLD) caused statistically significant reduction in CM-induced cytotoxicity. Overall, the data obtained suggest that CM induces neurotoxicity in SH-SY5Y cells by necroptosis.
Costa LG, Giordano G, Guizzetti M, Vitalone A. Neurotoxicity of pesticides: a brief review. Front Biosci. 2008; 13: 1240–1249.
Gupta A, Agarwal AK, Shukla GS. Effect of quinalphos and Cypermethrin exposure on developing blood–brain barrier: role of nitric oxide. EnvironToxicol Pharmacol. 2000; 2: 73–78.
Singh AK, Tiwari MN, Prakash O, Singh MP. A current review of cypermethrin-induced neurotoxicity and nigrostriatal dopaminergic neurodegeneration. Curr Neuropharmacol. 2012;10(1): 64–71.
Soderlund D. Molecular mechanisms of pyrethroid insecticide neurotoxicity: Recent advances. Arch Toxicol. 2012; 86: 165–181.
Hsieh HL, Wang HH, Wu WB, Chu PJ, Yang CM. Transforming growth factor-beta1 induces matrix metalloproteinase-9 and cell migration in astrocytes: roles of ROS-dependent ERK- and JNK-NF-kappaB pathways. J Neuroinflammation. 2010; 7: 1–17.
Tiwari MN. Singh AK, Israr A, Upadhyay G, Singh D, Patel DK, et al. Effects of cypermethrin on monoamine transporters, xenobiotic metabolizing enzymes and lipid peroxidation in the rat nigrostriatal system. Free Radic Res. 2010; 44: 1416–1424.
Gutteridge JM, Halliwell B. Antioxidants: molecules, medicines, and myths. Biochem Biophys Res Commun. 2010; 393: 561–564.
Maurya SK, Rai A, Rai NK, S. Deshpande S, Jain R, Mudiam MK, et al. Cypermethrin induces astrocyte apoptosis by the disruption of the autocrine/paracrine mode of epidermal growth factor receptor signaling. Toxicol Sci. 2012; 125: 473–487.
Mun JY, Lee WY, Han SS. Effects of cypermethrin on the dopaminergic neurons in the progressive hemiparkinsonian rats. Toxicol Mech Methods. 2005; 15: 399–404.
Flaskos J, Harris W, Sachana M, Munoz D, Tack J, Hargreaves AJ. The effects of diazinon and cypermethrin on the differentiation of neuronal and glial cell lines. Toxicol Appl Pharmacol. 2007; 219: 172–80.
Raszewski G, Lemieszek MK, Łukawski K, Juszczak M, Rzeski W. Chlorpyrifos and cypermethrin induce apoptosis in human neuroblastoma cell line SH-SY5Y. Basic Clin Pharmacol Toxicol. 2015; 116(2): 158–67.
Koh JY, Choi DW. Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. J Neurosci Methods. 1987; 20: 83–90.
Chan FK, Moriwaki K, De Rosa MJ. Detection of necrosis by release of lactate dehydrogenase activity. Methods Mol Biol. 2013; 979: 65–70.
Moquin D, Chan FK. The molecular regulation of programmed necrotic cell injury. Trends Biochem Sci. 2010; 35: 434–441.
Golstein P, Kroemer G. Cell death by necrosis: towards a molecular definition. Trends Biochem Sci. 2007; 32(1): 37–43.
Kakko I, Toimela T, Tähti H. The toxicity of pyrethroid compounds in neural cell cultures studied with total ATP, mitochondrial enzyme activity and microscopic photographing. Environ Toxicol Pharmacol. 2004; 15: 95–102.
Grajeda-Cota P, Ramírez-Mares MV, González de Mejía E. Vitamin C protects against in vitro cytotoxicity of cypermethrin in rat hepatocytes. Toxicol In Vitro. 2004; 18(1): 13–9.
Nikoletopoulou V, Markaki M, Palikaras K, Tavernarakis N. Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta. 2013; 1833(12): 3448–59.
Mitsiades N, Mitsiades C, Poulaki V, Chauhan D, Richardson P, Hideshima T, et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002; 99: 4525–4530.
He S, Wang L, Miao L, Wang T, Du F, Zhao L, et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 2009; 137: 1100–1111.
Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, et al. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 2009; 325: 332–336.
Holler N, Zaru R, Micheau O, Thome M , Attinger A, Valitutti S, et al. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol. 2000; 1: 489–495.
He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy, Annu Rev Genet. 2009; 43: 67–93.
Park JH, Lee JE, Shin IC, Koh HC. Autophagy regulates chlorpyrifos- induced apoptosis in SH-SY5Y cells. Toxicol Appl Pharmacol. 2013; 268: 55–67.
Zhu YX, Kortuem KM, Stewart AK. Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leuk Lymphoma. 2013; 54(4): 683–7.
Skulachev VP. Bioenergetic aspects of apoptosis, necrosis and mitoptosis, Apoptosis 2006; 11: 473–485.
Amaravadi RK, Thompson CB. The roles of therapy-induced autophagy and necrosis in cancer treatment. Clin Canc Res. 2007; 13: 7271–9.
Agrawal S, Singh A, Tripathi P, Mishra M, Singh PK, Singh MP. Cypermethrin-induced nigrostriatal dopaminergic neurodegeneration alters the mitochondrial function: a proteomics study. Mol Neurobiol. 2015; 51(2): 448–465.
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