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Quercetin Attenuates the Oxidative Injury–Mediated Upregulation of Apoptotic Gene Expression and Catecholaminergic Neurotransmitters of the Fetal Rats’ Brain Following Prenatal Exposure to Fenitrothion Insecticide

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Abstract

The association between gestational exposure to organophosphate and neurodevelopmental deficits is an area of particular interest, since the developing brain is sensitively susceptible to this neurotoxic pesticide. Instead, the neuroprotective role of quercetin has been suggested, but its exact protective mechanism against the developmental neurotoxicity of organophosphate did not previously notify. In this study, we have evaluated the anti-apoptotic role of quercetin against the developmental neurotoxicity of fenitrothion. Forty timed pregnant rats (from the 5th to the 19th day) were divided into four groups: control, quercetin (100 mg/kg/day), fenitrothion (2.31 mg/kg/day), and quercetin-fenitrothion co-treated groups where all animals received the corresponding doses by gavage. The embryotoxicity and many symptoms of the fetal growth retardation were recorded in the fenitrothion-intoxicated group. As compared with the control, fenitrothion brought significant (p < 0.05) elevation in the fetal brain dopamine, serotonin, and malondialdehyde levels as well as the activities of superoxide dismutase and catalase. However, fenitrothion decreased the glutathione concentration together with the activities of acetylcholinesterase, glutathione-S-transferase, and glutathione reductase. Moreover, fenitrothion induced some of the histopathological alterations in fetal brain and remarkably (p < 0.05) upregulated the mRNA gene expression of Bax and caspase-3 plus their protein immunoreactivity. It is worth mentioning that quercetin co-treatment alleviated (p ˂ 0.05) the fetal growth shortfalls, neurotransmission disturbances, lipid peroxidation, antioxidant disorders, and apoptosis evoked by fenitrothion with frequent repair to the control range. These results revealed that the downregulation of apoptosis-related genes and catecholamines is an acceptable indicator for the neuroprotective efficiency of quercetin especially during gestational exposure to organophosphate.

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References

  1. Aebi H (1984) [13] Catalase in vitro. Methods Enzymol 105:121–126. https://doi.org/10.1016/S0076-6879(84)05016-3

  2. Afshar S, Farshid AA, Heidari R, Ilkhanipour M (2008) Histopathological changes in the liver and kidney tissues of Wistar albino rat exposed to fenitrothion. Toxicol Ind Health 24:581–586. https://doi.org/10.1177/0748233708100090

  3. Ahmed MAE, Ahmed HI, El-Morsy EM (2013) Melatonin protects against diazinon-induced neurobehavioral changes in rats. Neurochem Res 38:2227–2236. https://doi.org/10.1007/s11064-013-1134-9

  4. Alam RT, Imam TS, Abo-Elmaaty AMA, Arisha AH (2019) Amelioration of fenitrothion induced oxidative DNA damage and inactivation of caspase-3 in the brain and spleen tissues of male rats by N-acetylcysteine. Life Sci 231:116534. https://doi.org/10.1016/j.lfs.2019.06.009

  5. Arnold SM, Morriss A, Velovitch J, Juberg D, Burns CJ, Bartels M, Aggarwal M, Poet T, Hays S, Price P (2015) Derivation of human biomonitoring guidance values for chlorpyrifos using a physiologically based pharmacokinetic and pharmacodynamic model of cholinesterase inhibition. Regul Toxicol Pharmacol 71:235–243. https://doi.org/10.1016/j.yrtph.2014.12.013

  6. Banni M, Messaoudi I, Said L, el Heni J, Kerkeni A, Said K (2010) Metallothionein gene expression in liver of rats exposed to cadmium and supplemented with zinc and selenium. Arch Environ Contam Toxicol 59:513–519. https://doi.org/10.1007/s00244-010-9494-5

  7. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10.1016/0003-2697(76)90527-3

  8. Bradman A, Barr DB, Henn BGC et al (2003) Measurement of pesticides and other toxicants in amniotic fluid as a potential biomarker of prenatal exposure: a validation study. Environ Health Perspect 111:1779–1782. https://doi.org/10.1289/ehp.6259

  9. Braun JB, Ruchel JB, Adefegha SA, Coelho APV, Trelles KB, Signor C, Castilhos LG (2017) Neuroprotective effects of pretreatment with quercetin as assessed by acetylcholinesterase assay and behavioral testing in poloxamer-407 induced hyperlipidemic rats. Biomed Pharmacother 88:1054–1063. https://doi.org/10.1016/j.biopha.2017.01.134

  10. Cao L, Tan C, Meng F, Liu P, Reece EA, Zhao Z (2016) Amelioration of intracellular stress and reduction of neural tube defects in embryos of diabetic mice by phytochemical quercetin. Sci Rep 6:1–11. https://doi.org/10.1038/srep21491

  11. Carlberg I, Mannervik B (1975) Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J Biol Chem 250:5475–5480

  12. Chen YC, Nagpal ML, Stocco DM, Lin T (2007) Effects of genistein, resveratrol, and quercetin on steroidogenesis and proliferation of MA-10 mouse Leydig tumor cells. J Endocrinol 192:527–537. https://doi.org/10.1677/JOE-06-0087

  13. Chen XP, Wang X, Dong JY (2011) Different reaction patterns of dopamine content to prenatal exposure to chlorpyrifos in different periods. J Appl Toxicol 31:355–359. https://doi.org/10.1002/jat.1598

  14. Chipuk JE, Green DR (2008) How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol 18(4):157–164. https://doi.org/10.1016/j.tcb.2008.01.007

  15. Costa LG, Garrick JM, Roquè PJ, Pellacani C (2016) Mechanisms of neuroprotection by quercetin: counteracting oxidative stress and more. Oxidative Med Cell Longev 2016:2986796

  16. Desforges M, Sibley CP (2010) Placental nutrient supply and fetal growth. Int J Dev Biol 54:377–390. https://doi.org/10.1387/ijdb.082765md

  17. Diamond A (2007) Consequences of variations in genes that affect dopamine in prefrontal cortex. Cereb Cortex 17:i161–i170. https://doi.org/10.1093/cercor/bhm082

  18. Downie T (1990) Theory and practice of histological techniques edited by J.D. Bancroft & a. Stevens, Churchill Livingstone, Edinburgh, 740 pages, £55.00. Histopathology 17:386–386. https://doi.org/10.1111/j.1365-2559.1990.tb00755.x

  19. Eleyan M, El-Desouky MA, Ibrahim KA et al (2018) Quercetin alleviates the adverse effects of nano-rich diesel exhaust particles on pregnancy and fetal growth in rats. Biosci Res 14:4590–4602

  20. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77. https://doi.org/10.1016/0003-9861(59)90090-6

  21. Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95. https://doi.org/10.1016/0006-2952(61)90145-9

  22. Fahmi AA, El-Desouky MA, Ibrahim KA, Abdelgaid HA (2018) Flaxseed alleviates toxic effects of some environmental pollutants on pregnant rats and their foetuses. Biosci Res 15:1832–1844

  23. Gabr GA, Soliman GA, Abdulaziz SS et al (2015) Teratogenic effects in rat fetuses subjected to the concurrent in utero exposure to emamectin benzoate insecticide. Pakistan J Biol Sci 18:333–340. https://doi.org/10.3923/pjbs.2015.333.340

  24. Gao FJ, Zhang SH, Xu P, Yang BQ, Zhang R, Cheng Y, Zhou XJ, Huang WJ, Wang M, Chen JY, Sun XH, Wu JH (2017) Quercetin declines apoptosis, ameliorates mitochondrial function and improves retinal ganglion cell survival and function in in vivo model of glaucoma in rat and retinal ganglion cell culture in vitro. Front Mol Neurosci 10:285. https://doi.org/10.3389/fnmol.2017.00285

  25. Gaspar P, Cases O, Maroteaux L (2003) The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci 4:1002–1012

  26. Ghahremani S, Soodi M, Atashi A (2018) Quercetin ameliorates chlorpyrifos-induced oxidative stress in the rat brain: possible involvment of PON2 pathway. J Food Biochem 42:e12530. https://doi.org/10.1111/jfbc.12530

  27. Gosselin EJ, Cate CC, Pettengill OS, Sorenson GD (1986) Immunocytochemistry: its evolution and criteria for its application in the study of epon-embedded cells and tissue. Am J Anat 175:135–160. https://doi.org/10.1002/aja.1001750205

  28. Granado-Serrano AB, Martín MA, Bravo L, Goya L, Ramos S (2012) Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: involvement of p38. Chem Biol Interact 195(2):154–164. https://doi.org/10.1016/j.cbi.2011.12.005

  29. Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

  30. Haq SH, AlAmro AA (2019) Neuroprotective effect of quercetin in murine cortical brain tissue cultures. Clin Nutr Exp 23:89–96. https://doi.org/10.1016/j.yclnex.2018.10.002

  31. Hassani S, Maqbool F, Salek-Maghsoudi A, Rahmani S, Shadboorestan A, Nili-Ahmadabadi A, Amini M, Norouzi P, Abdollahi M (2018) Alteration of hepatocellular antioxidant gene expression pattern and biomarkers of oxidative damage in diazinon-induced acute toxicity in wistar rat: a time–course mechanistic study. EXCLI J 17:57–71. https://doi.org/10.17179/excli2017-760

  32. Houghton PE, Mottola MF, Plust JH, Schachter CL (2000) Effect of maternal exercise on fetal and placental glycogen storage in the mature rat. Can J Appl Physiol 25:443–452

  33. Karampour NS, Arzi A, Varzi HN et al (2014) Quercetin preventive effects on theophylline-induced anomalies in rat embryo. Jundishapur J Nat Pharm Prod 9:e17834. https://doi.org/10.17795/jjnpp-17834

  34. Kaur S, Singla N, Dhawan DK (2019) Neuro-protective potential of quercetin during chlorpyrifos induced neurotoxicity in rats. Drug Chem Toxicol 42:220–230. https://doi.org/10.1080/01480545.2019.1569022

  35. Kinouchi S (2003) Changes in apoptosis-related genes (Bcl-2, Bax) in the urethras of old female rats following estrogen replacement. Yonago Acta Med 46:109–115

  36. Kumar A, Yegla B, Foster TC (2018) Redox signaling in neurotransmission and cognition during aging. Antioxid Redox Signal 28:1724–1745. https://doi.org/10.1089/ars.2017.7111

  37. Landgraf D, Barth M, Layer PG, Sperling LE (2010) Acetylcholine as a possible signaling molecule in embryonic stem cells: studies on survival, proliferation and death. Chem Biol Interact 187:115–119. https://doi.org/10.1016/j.cbi.2010.03.007

  38. Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of Pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474. https://doi.org/10.1111/j.1432-1033.1974.tb03714.x

  39. Masaki H, Okano Y, Ochiai Y, Obayashi K, Akamatsu H, Sakurai H (2002) α-Tocopherol increases the intracellular glutathione level in HaCaT keratinocytes. Free Radic Res 36:705–709. https://doi.org/10.1080/10715760210873

  40. Mehta A, Verma RS, Srivastava N (2009) Chlorpyrifos induced alterations in the levels of hydrogen peroxide, nitrate and nitrite in rat brain and liver. Pestic Biochem Physiol 94:55–59. https://doi.org/10.1016/j.pestbp.2009.04.001

  41. Meijer M, Brandsema JAR, Nieuwenhuis D, Wijnolts FM, Dingemans MM, Westerink RH (2015) Inhibition of voltage-gated calcium channels after subchronic and repeated exposure of PC12 cells to different classes of insecticides. Toxicol Sci 147:607–617. https://doi.org/10.1093/toxsci/kfv154

  42. Milošević MD, Paunović MG, Matić MM, Ognjanović BI, Saičić ZS (2018) Role of selenium and vitamin C in mitigating oxidative stress induced by fenitrothion in rat liver. Biomed Pharmacother 106:232–238. https://doi.org/10.1016/j.biopha.2018.06.132

  43. Mulder TA, van den Dries MA, Korevaar TIM, Ferguson KK, Peeters RP, Tiemeier H (2019) Organophosphate pesticides exposure in pregnant women and maternal and cord blood thyroid hormone concentrations. Environ Int 132:105124. https://doi.org/10.1016/j.envint.2019.105124

  44. Ouardi FZ, Anarghou H, Malqui H, Ouasmi N, Chigr M, Najimi M, Chigr F (2019) Gestational and lactational exposure to malathion affects antioxidant status and neurobehavior in mice pups and offspring. J Mol Neurosci 69:17–27. https://doi.org/10.1007/s12031-018-1252-6

  45. Prater MR, Laudermilch CL, Liang C, Holladay SD (2008) Placental oxidative stress alters expression of murine osteogenic genes and impairs fetal skeletal formation. Placenta 29:802–808. https://doi.org/10.1016/j.placenta.2008.06.010

  46. Quast SA, Berger A, Eberle J (2013) ROS-dependent phosphorylation of Bax by wortmannin sensitizes melanoma cells for TRAIL-induced apoptosis. Cell Death Dis 4:e839. https://doi.org/10.1038/cddis.2013.344

  47. Ryter SW, Hong PK, Hoetzel A et al (2007) Mechanisms of cell death in oxidative stress. Antioxidants Redox Signal 9:49–89

  48. Samad N, Saleem A, Yasmin F, Shehzad MA (2018) Quercetin protects against stress-induced anxiety- and depression-like behavior and improves memory in male mice. Physiol Res 67:795–808. https://doi.org/10.33549/physiolres.933776

  49. Sarikaya R, Selvi M, Erkoç F (2004) Investigation of acute toxicity of fenitrothion on peppered corydoras (Corydoras paleatus) (Jenyns, 1842). Chemosphere 56:697–700. https://doi.org/10.1016/j.chemosphere.2004.04.008

  50. Schuliga M, Chouchane S, Snow ET (2002) Upregulation of glutathione-related genes and enzyme activities in cultured human cells by sublethal concentrations of inorganic arsenic. Toxicol Sci 70:183–192

  51. Shawn BB, Gail W, Srinivasa MS, Xiao-Ming S, Michael B, Emad SA, Gerald MC (2001) Recruitment, activation and retention of caspases-9 and -3 by Apaf-1 apoptosome and associated XIAP complexes. EMBO J 20(5):998–1009. https://doi.org/10.1093/emboj/20.5.998

  52. Struve MF, Turner KJ, Dorman DC (2007) Preliminary investigation of changes in the sexually dimorphic nucleus of the rat medial preoptic area following prenatal exposure to fenitrothion. J Appl Toxicol 27:631–636. https://doi.org/10.1002/jat.1267

  53. Torres-Altoro MI, Mathur BN, Drerup JM, Thomas R, Lovinger DM, O’Callaghan JP, Bibb JA (2011) Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum. J Neurochem 119:303–313. https://doi.org/10.1111/j.1471-4159.2011.07428.x

  54. Turner KJ, Barlow NJ, Struve MF, Wallace DG, Gaido KW, Dorman DC, Foster PMD (2002) Effects of in utero exposure to the organophosphate insecticide fenitrothion on androgen-dependent reproductive development in the CRL:CD(SD) BR rat. Toxicol Sci 68:174–183. https://doi.org/10.1093/toxsci/68.1.174

  55. Villaverde J, Hildebrandt A, Martínez E, Lacorte S, Morillo E, Maqueda C, Viana P, Barceló D (2008) Priority pesticides and their degradation products in river sediments from Portugal. Sci Total Environ 390:507–513. https://doi.org/10.1016/j.scitotenv.2007.10.034

  56. Walker B (2000) Neurobehavioral toxicity. J Natl Med Assoc 92:116–124

  57. Wills ED (1966) Mechanisms of lipid peroxide formation in animal tissues. Biochem J 99:667–676. https://doi.org/10.1042/bj0990667

  58. Yang K, Shi Y, Song Y et al (2009) P,p′-DDE induces apoptosis of rat sertoli cells via a fasl-dependent pathway. J Biomed Biotechnol 2009

  59. Yin H, Xu L, Porter NA (2011) Free radical lipid peroxidation: mechanisms and analysis. Chem Rev 111:5944–5972

  60. Yuan JS, Reed A, Chen F, Stewart CN (2006) Statistical analysis of real-time PCR data. BMC Bioinformatics 7:85. https://doi.org/10.1186/1471-2105-7-85

  61. Zucca FA, Segura-Aguilar J, Ferrari E, Muñoz P, Paris I, Sulzer D, Sarna T, Casella L, Zecca L (2017) Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson’s disease. Prog Neurobiol 155:96–119

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Correspondence to Khairy A. Ibrahim.

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Ibrahim, K.A., Eleyan, M., Abd El-Rahman, H.A. et al. Quercetin Attenuates the Oxidative Injury–Mediated Upregulation of Apoptotic Gene Expression and Catecholaminergic Neurotransmitters of the Fetal Rats’ Brain Following Prenatal Exposure to Fenitrothion Insecticide. Neurotox Res (2020). https://doi.org/10.1007/s12640-020-00172-6

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Keywords

  • Fenitrothion
  • Gestational exposure
  • Rat
  • Brain
  • Apoptosis
  • Quercetin