The subcronic effects of acetamipride on the global DNA methylation levels in Sprague-Dawley rat brain and liver
Acetamiprid, which is a neonicotinoid insecticide, is used to control leafy vegetables, fruiting vegetables, fir seeds, citrus fruits,
pome fruits, grapes, cotton and ornamental plants and absorbent insects on flowers. The present study aim to evaluate global
DNA methylation and gene expression of DNA methylation related enzymes in liver and brain tissues of male Sprague-Dawley
rats after a 90-day subchronic exposure to acetamiprid at low doses of 12.5, 25 and 35 mg/kg body weight (b.w.). Global DNA
methylation resulted in a significant decrease in the levels of 5-methylcytosine (5-mC%) at the doses of 25 and 35 mg/kg b.w.
in the liver and 35 mg/kg b.w. in the brain compared to the vehicle control group. Consistently, expression of DNA methyltransferase enzymes decreased at doses of 12.5, 25 and 35 mg/kg b.w. in liver and 35 mg/kg b.w. in brain. It has been suggested that
non-genotoxic (epigenetic) mechanisms may be involved in the toxicity of acetamiprid and further investigations are needed
to elucidate the epigenetic effects of neonicotinoid insecticides.
Cite this article as: Arıcan YE, Karaman EF, Özden S (2019). The subcronic effects of acetamipride on the global DNA methylation levels in Sprague-Dawley rat brain and liver. Istanbul J Pharm 49 (3): 167-172.
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- • Anderson OS, Sant KE, Dolinoy DC (2012). Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem 23: 853-859.
• Baccarelli A, Bollati V (2009). Epigenetics and environmental
chemicals. Curr Opin Pediatr 21: 243-251.
• Bansal A, Pinney SE (2017). DNA methylation and its role in the
pathogenesis of diabetes. Pediatr Diabetes 18: 167-177.
• Baylin SB (1997). Tying it all together: epigenetics, genetics, cell
cycle, and cancer. Science 277: 1948-1949.
• Baylin SB, Hoppener JW, de Bustros A, Steenbergh PH, Lips CJ,
Nelkin BD (1986). DNA methylation patterns of the calcitonin
gene in human lung cancers and lymphomas. Cancer Res 46:
2917-2922.
• Casida J, Quistad GB (2004). Why insecticides are more toxic to
insect than people: the unique toxicology of insects. J Pest Sci 29:
81-86.
• Chakroun S, Ezzi L, Grissa I, Kerkeni E, Neffati F, Bhouri R, Sallem A,
Najjar MF, Hassine M, Mehdi M, Haouas Z, Ben Cheikh H (2016).
Hematological, biochemical, and toxicopathic effects of subchronic acetamiprid toxicity in Wistar rats. Environ Sci Pollut Res
Int 23: 25191-25199.
• Chen LM, Liu HS, Chen N, Du SM (2007). The determination of
acetamiprid residues om serum by gas chromatography. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 25: 191-192.
• Collotta M, Bertazzi PA, Bollati V (2013). Epigenetics and pesticides. Toxicology 307: 35-41.
• Çavaş T, Çinkılıç N, Vatan Ö, Yılmaz D (2014). Effects of fullerenol
nanoparticles on acetamiprid induced cytoxicity and genotoxicity in cultured human lung fibroblasts. Pestic Biochem Phys 114:
1-7.
• Çavaş T, Çinkılıç N, Vatan Ö, Yılmaz D, Coşkun M (2012). In vitro
genotoxicity evaluation of acetamiprid in CaCo-2 cells using
the micronucleus, comet and γH2AX foci assays. Pestic Biochem
Physiol 104: 212-217.
• Desaulniers D, Xiao GH, Lian H, Feng YL, Zhu J, Nakai J, Bowers WJ
(2009). Effects of mixtures of polychlorinated biphenyls, methylmercury, and organochlorine pesticides on hepatic DNA methylation in prepubertal female Sprague-Dawley rats. Int J Toxicol
28: 294-307.
• Devan RS, Mishra A, Prabu P, Mandal T, Panchapakesan S (2015).
Sub-chronic oral toxicity of acetamiprid in wistar rats. Toxıcol Environ Chem 97: 1236-1252.
• Dich J, Zahm SH, Hanberg A, Adami HO (1997). Pesticides and
cancer. Cancer Causes Control 8: 420-443.
• European Food Safety Authority (EFSA) 2016. Peer review of the
pesticide risk assessment of the active substance acetamiprid.
EFSA Journal 14: 1-26.
• EFSA Panel On Plant Protection Products And Their Residues
(PPR) (2013). Scientific Opinion on the developmental neurotoxicity potential of acetamiprid and imidacloprid, Scientific Opinion, European Food Safety Authority (EFSA) Journal, 1-47.
• Ford KA (2008). Metabolism, Pharmacokinetics and Toxicology of
the Neonicotinoid Insecticides in Mice. 1-7. Berkeley, ABD: University of California, Molecular Toxicology.
• Ford KA, Gulevich AG, Swenson TL, Casida JE (2011). Neonicotinoid insecticides: oxidative stress in planta and metallo-oxidase
inhibition. J Agric Food Chem 59: 4860-4867.
• Gama-Sosa MA, Slagel VA, Trewyn RW, Oxenhandler R, Kuo KC,
Gehrke CW, Ehrlich M (1983). The 5-methylcytosine content of
DNA from human tumors. Nucleic Acids Research 11: 6883-6894.
• Gasmi S, Kebieche M, Rouabhi R, Touahria C, Lahouel A, Lakroun
Z, Henine S, Soulimani R (2017). Alteration of membrane integrity
and respiratory function of brain mitochondria in the rats chronically exposed to a low dose of acetamiprid. Environ Sci Pollut Res
Int 24: 22258-22264.
• Gasmi S, Rouabhi R, Kebieche M, Salmi A, Boussekine S, Toualbia
N, Taib C, Henine S, Bouteraa Z, Djabri B (2016). Neurotoxicity of
acetamiprid in male albino rats and the opposite effect of quercetin. Biotechnol Ind J 12: 113.
• Greally JM, Jacobs MN (2013). In vitro and in vivo testing methods
of epigenomic endpoints for evaluating endocrine disruptors. Altex 30: 445-471.
• Green T, Toghill A, Lee R, Waechter F, Weber E, Noakes J (2005).
Thiamethoxam induced mouse liver tumors and their relevance
to humans part 1: mode of action studies in the mouse. Toxicol
Sci 86: 36-47.
• Honda H, Tomizawa M, Casida JE (2006). Neonicotinoid metabolic
activation and inactivation established with coupled nicotinic receptor-CYP3A4 and -aldehyde oxidase systems. Toxicol Lett 161:
108-114.
• Ivkovic B, Kitanovic N, Fa S, Andric N (2018). Effects of acetamiprid
on gene-specific DNA methylation in zebrafish (Danio rerio) embryos. In Serbian Biochemical Society Eighth Conference (p. 133).
• Jones PA, Baylin SB (2007). The epigenomics of cancer. Cell 128:
683-692.
• Kanthasamy A, Jin H, Anantharam V, Sondarva G, Rangasamy
V, Rana A (2012). Emerging neurotoxic mechanisms in environmental factors-induced neurodegeneration. Neurotoxicology 33:
833-837.
• Kanungo D, Solecki R (2011). Pesticide residues in food toxicological evaluations. In: WHO, & FAO (Eds), Joint Meeting of the FAO
Panel of Experts on Pesticide Residues in Food and the Environment
and the WHO Core Assessment Group on Pesticide Residues. 2, pp.
3-92. Geneva, Switzerland,: World Health Organization.
• Karaman EF, Ozden S (2019). Alterations in global DNA methylation and metabolism-related genes caused by zearalenone in
MCF7 and MCF10F cells. Mycotoxin Res 35: 309-320.
• Kim KY, Kim DS, Lee SK, Lee IK, Kang JH, Chang YS, Jacobs DR,
Steffes M, Lee DH (2010). Association of low-dose exposure to
persistent organic pollutants with global DNA hypomethylation
in healthy Koreans. Environ Health Perspect 118: 370-374.
• Kiriyama K, Itazu Y, Kagabu S, Nishimura K (2003). Insecticidal and
neuroblocking activities of acetamiprid and related compounds.
J Pest Sci 28: 8-17.
• Kocaman AY, Topaktaş M (2007). In vitro evaluation of the genotoxicity of acetamiprid in human peripheral blood lymphocytes.
Environ Mol Mutagen 48: 483-490.
• Kulis M, Esteller M (2010). DNA methylation and cancer. Adv Genet
70: 27-56.
• Mandal PS, Mondal S, Karnam SS, Purohit K (2015). A behavioral
study on learning and memory in adult sprague dawley rat in
ınduced acetamiprid toxicity. Explor Anim Med Res 5: 27-32.
• Maqbool F, Mostafalou S, Bahadar H, Abdollahi M (2016). Review
of endocrine disorders associated with environmental toxicants
and possible involved mechanisms. Life Sci 145: 265-273.
• Mondal S, Ghosh RC, Karnam SS, Purohit K (2014). Toxicopathological changes on wistar rat after multiple exposures to acetamiprid. Vet World 7: 1058-1065.
• Moggs JG, Goodman JI, Trosko JE, Roberts RA (2004). Epigenetics
and cancer: implications for drug discovery and safety assessment. Toxicol Appl Pharmacol 196: 422-430.
• Muranli FDG, Rasgele PG, Kekecoglu M, Kanev M, Özdemir K
(2015). Potential genotoxicity of acetamiprid and propineb singly or in combination in cultured human peripheral blood lymphocytes by using MN Assay. Fresenius Environmental Bulletin 24:
3947-3955.
• Office of Prevention, Pesticides and Toxic Substances (2003). Pesticide Thiacloprid Fact Sheet. Environmental Protection Agency
(EPA). Washington, DC: United States.
• Sanyal D, Chakma D, Alam S (2008). Persistence of a neonicotinoid insecticide, acetamiprid on chili (Capsicum annum l.). Bull
Environ Contam Toxicol 81: 365-368
• Shutoh Y, Takeda M, Ohtsuka R, Haishima A, Yamaguchi S, Fujie H,
Komatsu Y, Maita K, Harada T (2009). Low dose effects of dichlorodiphenyltrichloroethane (DDT) on gene transcription and DNA
methylation in the hypothalamus of young male rats: implication
of hormesis-like effects. J Toxicol Sci 34: 469-482.
• Simon-Delso N, Amaral-Rogers V, Belzunces LP, Bonmatin JM,
Chagnon M, Downs C (2015). Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites.
Environ Sci Pollut Res Int 22: 5-34.
• Terayama H, Endo H, Tsukamoto H, Matsumoto K, Umezu M,
Kanazawa T, Ito M, Sato T, Naito M, Kawakami S, Fujino Y, Tatemichi M, Sakabe K (2016). Acetamiprid accumulates in different
amounts in murine brain regions. Int J Environ Res Public Health
13: 1-13.
• Tomizawa M, Casida JE (2003). Selective toxicity of neonicotinoids
attributable to specificity of insect and mammalian nicotinic receptors. Annu Rev Entomol 48: 339-364.
• Ünver S, Uysal H (2014). Neonikotinoid insektisitlere bağlı
olarak Drosophila melanogaster’in AChE aktivitesinde meydana
gelen değişikliklerin bitkisel ekstraktlar ile giderilmesi üzerine
araştırmalar. Fen Bilimleri Dergisi (CFD), 35(4).
• Wang W, Otsuka S, Nansai H, Ito T, Abe K, Nakao Y, Ohgane J, Yoneda M, Sone H (2019). Epigenetic Effects of Exposure to Insecticide
on Early Differentiation of Mouse Embryonic Stem Cells. BioRxiv
628487.
• Watson RE, Goodman JI (2002). Epigenetics and DNA methylation come of age in toxicology. Toxicol Sci 67: 11-16.
• Whitacre DM, Ware GW (2004). An Introduction to Insecticides.
(Radcliffe EB, Hutchison WD, editors, and University of Minnesota;
Department of Entomology; College of Food, Agricultural, and
Natural Resource Sciences) Retrieved from Radcliffe’s IPM World
Textbook: https://ipmworld.umn.edu/ware-intro-insecticides,
Accessed 13.03.2017
• Xu HX, Qin JZ, Zhang KY, Zeng WX (2015). Dynamic expression
profile of DNA methyltransferases in rat testis development. Pol
J Vet Sci 18: 549-556.
• Yamamoto I, Casida JE (1999). Nicotinoid insecticides and the nicotinic acetylcholine receptor. Tokyo: Springer-Verlag.
• Yao X-H, Jin S, Lv Z-M (2006). Response of superoxide dismutase,
catalase, and ATPase activity in bacteria exposed to acetamiprid.
Biomed Environ S 19: 309-314.
• Yu SJ (2008). The Need for Pestisides and Their Pattern of Use. In:
Yu SJ (ed.) The Toxicology and Biochemistry of Insecticides (pp.
1-6). New York, USA: CRC Press.
• Zhang JJ, Wang Y, Xiang HY, Li MX, Li WH, Ma KG, Wang XZ, Zhang
JH (2011). Oxidative stress: role in acetamiprid-induced ımpairment
of the male mice reproductive system. Agric Sci China 10: 786-796.