Teratogenic effects of imidacloprid in rats: mechanistic role of oxidative stress

  • Authors

    • Nermeen Borai El-Borai Associate Prof. of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, University of Sadat City
    • Seham Said Hadad Lecturer of Anatomy & Embryology
    • Hanem Kamal Khalifa Lecturer of Biochemistry and Chemistry of Nutrition
    2019-11-17
    https://doi.org/10.14419/ijpt.v7i2.29828
  • Imidacloprid, Malformations, Oxidative Stress, Placenta, Teratogenicity.

  • Extensive use of imidacloprid (IMI) insecticide in the agro-vet practices leads to continuous animal and human exposure. Exposure of pregnant dams to such insecticides results in fetal malformations. In the light of this, the present study was designed to investigate the teratogenic effects of two different doses of IMI and the possible mechanistic role of oxidative stress. Fifteen pregnant females were randomly divided into three equal groups and orally treated daily during organogenesis period (6-15th GD), control (distilled water), LD-IMI (45 mg/kg) and HD-IMI (90 mg/kg). All pregnant dams were exposed to caesarean section on GD 20. Exposure to IMI induced significant increase in the percentage of resorptions at high-dose with significant reduction of fetal and placental weights in a dose-dependent manner. External fetal morphological abnormalities were recorded only at high-dose while several visceral abnormalities were observed in fetuses at low- and high-doses. Significant increases in the percentages of fetal skeletal malformations were recorded only in the high-dose group. Significant changes in MDA, GSH levels and CAT activity with insignificant change in the level of H2O2 were recorded only in placentae of LD-IMI group. However, all these parameters recorded significant changes in serum of dams, placentae and liver of fetuses at high-dose. In conclusion, exposure of pregnant rats to IMI, particularly at higher-dose, during the period of organogenesis induced fetal teratogenic effects that may be related to its maternal and fetal oxidative damaging impacts.

     

     

     

  • References

    1. [1] Abou-Donia MB, Goldstein LB, Bullman S, Tu T, Khan WA, Dechkovskaia AM and Abdel-Rahman AA (2008). Imidacloprid induces neurobehavioral deficits and increases expression of glial fibrillary acidic protein in the motor cortex and hippocampus in offspring rats following in utero exposure. J Toxicol Environ Health A 71(2), 119-30. https://doi.org/10.1080/15287390701613140.

      [2] Abu-Qare AW, Elmasry E and Abou-Donia MB (2003). A role for P- glycoprotein in environmental toxicology. J Toxicol Environ Health B Crit Rev 6, 279–288. https://doi.org/10.1080/10937400306466.

      [3] Adjrah Y, Karou SD, Agbonon A, Ameyapoh Y, de Souza C and Gbeassor M (2013). Effect of cypermethrin-treated lettuce (Lactuca sativa) on wistar rat liver. J. Appl. Pharmacol. Sci. 3, 128–132. https://doi.org/10.7324/JAPS.2013.30125.

      [4] Aebi H. (1984). Catalase in vitro. Methods Enzymol. 105, 121–26. https://doi.org/10.1016/S0076-6879(84)05016-3.

      [5] Ahmed MM and Nasr SA (2015). Protective Effect of Broccoli and Ferulic Acid on Imidacloprid-Induced Hepatotoxicity in Rat. The Egyptian Journal of Biochemistry & Molecular Biology 33, 1-15. https://doi.org/10.21608/ejb.2015.9697.

      [6] Anatra-Cordone M and Durkin P (2005). Imidacloprid. Human health assessment and ecological risk assessment Final report. Syracuse Environmental Research Associates, Inc., New York, SERA TR 05- 43-24-03a.

      [7] Arfat Y, Mahmood N, Tahir MU, Rashid M, Anjum S, Zhao F, Li DJ, Sun YL, Hu L, Zhihao C, Yin C, Shang P and Qian AR (2014). Effect of imidacloprid on hepatotoxicity and nephrotoxicity in male albino mice. Toxicology Reports 1, 554-561. https://doi.org/10.1016/j.toxrep.2014.08.004.

      [8] Bagri P, Kumar V and Sikka AK (2016). Assessment of imidacloprid- induced mutagenic effects in somatic cells of Swiss albino male mice. Drug Chem Toxicol. 39(4), 412-7. https://doi.org/10.3109/01480545.2015.1137301.

      [9] Bal R, Türk G, Tuzcu M, Yilmaz O, Kuloglu T, Gundogdu R, Gür S, Agca A, Ulas M, Cambay Z, Tuzcu Z, Gencoglu H, Guvenc M, Ozsahin AD, Kocaman N, Aslan A and Etem E (2012). Assessment of imidacloprid toxicity on reproductive organ system of adult male rats. J Environ Sci Health B. 47(5), 434-44. https://doi.org/10.1080/03601234.2012.663311.

      [10] Bashandy SA, Bashandy MA, El Zawahry EI, Adly F and Abdel Naby MF (2017). Beta Carotene and Hesperidin Antioxidants Mitigate Hepatotoxic Effects of Imidacloprid in Male Rats. Al Azhar Bulletin of Science 28(1), 15-27. https://doi.org/10.21608/absb.2017.8164.

      [11] Beutler EK, Duron O and Kefly BM. (1963). Improved method for the determination of blood glutathione. J. Lab. Clin. Med. 61, 882-888.

      [12] Bonmatin JM, Giorio C, Girolami V, Goulson D, Kreutzweiser DP, Krupke C, Liess M, Long E, Marzaro M, Mitchell AE, Noome DA, Simon-Delso N, and Tapparo A (2015). Environmental fate and exposure; neonicotinoids and fipronil. Environ Sci Pollut Res Int. 22, 35–67. https://doi.org/10.1007/s11356-014-3332-7.

      [13] Burton GJ and Jauniaux E (2011). Oxidative stress. Best Practice &Research. Clinical Obstetrics & Gynaecology 25, 287–299. https://doi.org/10.1016/j.bpobgyn.2010.10.016.

      [14] Chakroun S, Grissa I, Ezzi L, Ammar O, Neffati F, Kerkeni E, Najjar MF, Haouas Z and Ben Cheikh H (2017). Imidacloprid enhances liver damage in Wistar rats: Biochemical, oxidative damage and histological assessment. Journal of Coastal Life Medicine 5(12), 540-546. https://doi.org/10.12980/jclm.5.2017J7-149.

      [15] Coughlan MT, Vervaart PP, Permezel M, Georgiou HM and Rice GE (2004). Altered placental oxidative stress status in gestational diabetes mellitus. Placenta 25, 78–84. https://doi.org/10.1016/S0143-4004(03)00183-8.

      [16] Desforges, M and Sibley CP (2010). Placental nutrient supply and fetal growth. Int. J. Dev. Biol. 54, 377-390. https://doi.org/10.1097/MCO.0b013e32835e3674.

      [17] Duzguner V and Erdogan S (2012). Chronic exposure to imidacloprid induces inflammation and oxidative stress in the liver & central nervous system of rats. Pesticide biochemistry and physiology 104(1), 58-64. https://doi.org/10.1016/j.pestbp.2012.06.011.

      [18] El Ghareeb AEW, Hamdi H, Taha ESF and Ali H (2015). Evaluation of teratogenic potentials of bronchodilator drug on offsprings of albino rats. Int. J. Scient. Eng. Res. 6, 534-542. https://doi.org/10.14299/ijser.2015.03.005.

      [19] El-Sabbagh HS, Khamiss OA, El-Borai NB and El-Khadrawey BA (2018). The Potential Therapeutic Value of Green Tea and Thyme Aqueous Extracts on Imidacloprid Toxicity in Rats, IJMPR 2(4), 59-67.

      [20] Gawade L, Dadarkar SS, Husain R, and Gatne M (2013). A detailed study of developmental immunotoxicity of imidacloprid in Wistar rats. Food and Chemical Toxicology 51, 61–70. https://doi.org/10.1016/j.fct.2012.09.009.

      [21] Goulson D. (2013): An overview of the environmental risks posed by neonicotinoid insecticides. J Appl Ecol. 50, 977–987. https://doi.org/10.1111/1365-2664.12111.

      [22] Hamid S, Mahajan R and Singh H (2012). Carbaryl, A Pesticide Causes "Toxic Hepatitis in Albino Rats. J Cytol Histol 3, 4. https://doi.org/10.4172/2157-7099.1000149.

      [23] Holzum B (1996). YRC 2894 – Developmental toxicity study in rabbits after oral administration. Unpublished report No. 24709, edition No. M-000780-01-1, dated 26 January 1996, from Bayer AG, Wuppertal, Germany. Submitted to WHO by Bayer CropScience AG, Monheim, Germany.

      [24] Houghton PE, Mottola MF, Plust JH and Schachter CL (2000). Effect of maternal exercise on fetal and placental glycogen storage in the mature rat. Can. J. Applied Physiol. 25, 443-452. https://doi.org/10.1139/h00-029.

      [25] Hussein M, Singh V, Hassan MA, Singh AK and Yadav B (2014). Malformations and Teratogenic Effects of Imidacloprid on Chick Embryo. Sch. J. App. Med. Sci. 2(1A), 67-72.

      [26] Jauniaux E, Poston L and Burton GJ (2006). Placental-related diseases of pregnancy: involvement of oxidative stress and implications in human evolution. Human Reproduction Update 12, 747–755. https://doi.org/10.1093/humupd/dml016.

      [27] Jeschke P, Nauen R, Schindler M and Elbert A. (2011). Overview of the status and global strategy for neonicotinoids. J Agric Food Chem 59(7):2897-908. https://doi.org/10.1021/jf101303g.

      [28] Kapoor U, Srivastava MK and Srivastava LP (2011). Toxicological impact of technical imidacloprid on ovarian morphology, hormones and antioxidant enzymes in female rats. Food Chem Toxicol 49, 3086-9. https://doi.org/10.1016/j.fct.2011.09.009.

      [29] Kapoor U, Srivastava MK, Bhardwaj S and Srivastava LP (2010). Effect of imidacloprid on antioxidant enzymes and lipid peroxidation in female rats to derive its No Observed Effect Level (NOEL). J Toxicol Sci. 35(4), 577-81. https://doi.org/10.2131/jts.35.577.

      [30] Lonare M, Kumar M, Raut S, Badgujar P, Doltade S and Telang A (2014). Evaluation of imidacloprid-induced neurotoxicity in male rats: a protective effect of curcumin. Neurochem Int.78, 122-9. https://doi.org/10.1016/j.neuint.2014.09.004.

      [31] Lonare M, Kumar M, Raut S, More A, Doltade S, Badgujar P and Telang A (2016). Evaluation of ameliorative effect of curcumin on imidacloprid-induced male reproductive toxicity in Wistar rats. Environ Toxicol 10, 1250-63. https://doi.org/10.1002/tox.22132.

      [32] Manson GM, and Kang YG (1994). Test method for assessing female reproductive and developmental toxicology. In "Principles and Methods of Toxicology", 2nd Ed., by A. Wallace Hayes, Raven Press, Ltd., New York. https://doi.org/10.1201/b14258-38.

      [33] Mathieu-Denoncourt J, Wallace SJ, de Solla SR and Langlois VS (2015). Plasticizer endocrine disruption: highlighting developmental and reproductive effects in mammals and non-mammalian aquatic species. Gen. Comp. Endocrinol. 219, 74–88. https://doi.org/10.1016/j.ygcen.2014.11.003.

      [34] Matsuda K, Buckingham SD, Kleier D, Rauh JJ, Grauso M and Sattelle DB (2001). Neonicotinoids: insecticides acting on insect nicotinic acetylcholine receptors. Trends in Pharmacological Sciences 22(11), 573-580. https://doi.org/10.1016/S0165-6147(00)01820-4.

      [35] Mohany M, Badr G, Refaat I and El-Feki M (2011). Immunological and histological effects of exposure to imidacloprid insecticide in male albino rats. African Journal of Pharmacy and Pharmacology 5(18), 2106-2114. https://doi.org/10.5897/AJPP11.625.

      [36] Myatt L and Cui X (2004). Oxidative stress in the placenta. Histochem Cell Biol 122, 369–382. https://doi.org/10.1007/s00418-004-0677-x.

      [37] Nagai R, Watanabe K, Wakatsuki A, Hamada F, Shinohara K, Hayashi Y, Imamura R and Fukaya T (2008). Melatonin preserves fetal growth in rats by protecting against ischemia/ reperfusion-induced oxidative/nitrosative mitochondrial damage in the placenta. Journal of Pineal Research 45, 271–276. https://doi.org/10.1111/j.1600-079X.2008.00586.x.

      [38] Ohkawa H, Ohishi W and Yagi K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95, 351- 358. https://doi.org/10.1016/0003-2697(79)90738-3.

      [39] Otranto D, Colella V, Crescenzo G, Basano FS, Nazzari R, Capelli G, Petry G, Schaper R, Pollmeier M, Mallia E, Dantas-Torresa F and PaoloLi R (2016). Efficacy of moxidectin 2.5% and imidacloprid 10% in the treatment of ocular thelaziosis by Thelazia callipaeda in naturally infected dogs.Veterinary Parasitology 227, 118-121. https://doi.org/10.1016/j.vetpar.2016.07.035.

      [40] Dennery PA (2007). Effects of Oxidative Stress on Embryonic Development. Birth Defects Research (Part C) 81,155–162. https://doi.org/10.1002/bdrc.20098.

      [41] Paumgartten FJR, De-Carvalho RR, Souza K, Madi CAM and Chahoud I (1998). Study of the effectsof β-myrcene on rat fertility and general reproductive performance. Braz. J. Med. Biol. Res. 31, 955-965. https://doi.org/10.1590/S0100-879X1998000700012.

      [42] Pfeil R and Tasheva M (2006). Thiacloprid. Thiacloprid X-X JMPR. Available from: apps.who.int/pesticide-residues-jmprdatabase/ Document/140.

      [43] Sarker AH, Watanabe S, Seki S, Akiyama T and Okada S (1995). “Oxygen radical-induced single-strand DNA breaks and repair of the damage in a cell-free system,†Mutation Research 337(2), 85–95. https://doi.org/10.1016/0921-8777(95)00012-9.

      [44] Schardein JL (2011). Reproduction range-finding study in mated rats, 1991. Unpublished report No. 449-018 from International Research and Development Corporation, Mattawan, MI, USA. Submitted to WHO by Nippon Soda Co., Ltd, Tokyo, Japan. In: Kanungo D, and Solecki R. 2011. Acetamiprid. In Pesticide Residues in Food. Toxicological Evaluations. Joint FAO/Who Meeting on Pesticide Residues. Geneva, Switzerland 20-29, 3-92.

      [45] Sheets LP, Li AA, Minnema DJ, Collier RH, Creek MR and Peffer RC (2016). A critical review of neonicotinoid insecticides for developmental neurotoxicity. Crit Rev Toxicol 46(2), 153–190. https://doi.org/10.3109/10408444.2015.1090948.

      [46] Simon-Delso N, Amaral-Rogers V, Belzunces LP, Bonmatin JM, Chagnon M, Downs C, et al. (2015). Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites. Environ Sci Pollut Res Int 22(1), 5-34. https://doi.org/10.1007/s11356-014-3470-y.

      [47] Singh S, Pandey A, Sharma B, Lawrence K and Pandit S (2013). Imidacloprid induced osmotic fragility in erythrocytes of rats: Protective role of vit.C and tea. IOSR Journal of Environmental Science, Toxicology and Food Technology 5 (5), 103-105. https://doi.org/10.9790/2402-055103105.

      [48] Stahl B (1997). YRC 2894 –Developmental toxicity in rats after oral administration. Unpublished report No. 26132, edition No. M-000832-01-1, dated 25 March 1997, from Bayer AG, Wuppertal, Germany. Submitted to WHO by Bayer CropScience AG, Monheim, Germany.

      [49] Sun M, Kingdom J, Baczyk D, Lye SJ, Matthews SG and Gibb W (2006). Expression of the multidrug resistance P-glycoprotein, (ABCB1 glycoprotein) in the human placenta decreases with advancing gestation. Placenta 27(6/7), 602–609. https://doi.org/10.1016/j.placenta.2005.05.007.

      [50] Taira K (2014): Human neonicotinoids exposure in Japan. Jpn J Clin Ecol. 23 (1),14-24.

      [51] Tomizawa M and Casida JE (2005). Neonicotinoid insecticide toxicology: mechanisms of selective action. Annu Rev Pharmacol Toxicol. 45, 247-68. https://doi.org/10.1146/annurev.pharmtox.45.120403.095930.

      [52] Trutter JA (2011). Two-generation reproduction study with NI-25 in rats (reproduction and fertility effects), 1999. Unpublished report No. Covance 6840-108 from Covance Laboratories Inc., Vienna, VA, USA. Submitted to WHO by Nippon Soda Co., Ltd, Tokyo, Japan, 1999. In: Kanungo D, and Solecki R. 2011. Acetamiprid. In Pesticide Residues in Food. Toxicological Evaluations. Joint FAO/Who Meeting on Pesticide Residues. Geneva, Switzerland 20-29, 3-92.

      [53] Vohra P and Khera KS (2015): A Three Generation Study with Effect of Imidacloprid in Rats: Biochemical and Histopathological Investigation. Toxicol Int. 22(1): 119–124. https://doi.org/10.4103/0971-6580.172270.

      [54] Wang T, Chen M, Yan YE, Xiao FQ, Pan XL and Wang H (2009). Growth retardation of fetal rats exposed to nicotine in utero: Possible involvement of CYP1A1, CYP2E1, and P-glycoprotein. Environ Toxicol 24, 33–42. https://doi.org/10.1002/tox.20391.

      [55] Watson ED and Cross JC (2005). Development of structures and transport functions in the mouse placenta. Physiology (Bethesda) 20, 180–193. https://doi.org/10.1152/physiol.00001.2005.

  • Downloads

  • How to Cite

    Borai El-Borai, N., Said Hadad, S., & Kamal Khalifa, H. (2019). Teratogenic effects of imidacloprid in rats: mechanistic role of oxidative stress. International Journal of Pharmacology and Toxicology, 7(2), 35-43. https://doi.org/10.14419/ijpt.v7i2.29828