Quercetin Mitigates Acetamiprid-Induced Memory Impairment and Neuronal Damage in Rats

Document Type : Original paper


1 Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

2 Institute for Natural Products and Medicinal Plants, Tarbiat Modares University, Tehran, Iran.

3 Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.



Background and objectives: Acetamiprid, a widely used neonicotinoid pesticide in agriculture, acts as a stimulant on nicotinic acetylcholine receptors, potentially causing neurotoxicity. Quercetin, a neuroprotective flavonoid found in fruits and vegetables, shows promise in mitigating neurological disorders. This study investigated quercetin's protective potential against acetamiprid-induced memory impairment. Methods: Male rats were divided into four groups: control, acetamiprid (40 mg/kg), quercetin (20 mg/kg), and a combination of acetamiprid and quercetin, administered orally for 28 days. Cognitive performance was assessed using the Morris water maze test; oxidative stress markers in the hippocampus were evaluated, along with histological analysis. Results: Rats exposed to 40 mg/kg acetamiprid exhibited significant memory impairment. Notably, co-treatment with quercetin reversed this effect. Acetamiprid induced oxidative stress, as indicated by increased lipid peroxidation, reduced thiol content, and decreased catalase (CAT) enzyme activity. Simultaneous quercetin and acetamiprid administration effectively mitigated these oxidative stress markers. Histological analysis demonstrated quercetin's ability to prevent acetamiprid-induced hippocampal neuronal damage. Conclusion: Quercetin shows promise in ameliorating acetamiprid-induced memory deficits and neuronal damage, making it a potentially valuable nutraceutical, especially for individuals exposed to pesticides like agricultural workers.


Main Subjects

  • Tomizawa M, Casida JE. Selective toxicity of neonicotinoids attributable to specificity of insect and mammalian nicotinic receptors. Annu Rev Entomol. 2003; 48(1): 339-364.
  • Tomizawa M, Casida JE. Neonicotinoid insecticide toxicology: mechanisms of selective action. Annu Rev Pharmacol Toxicol. 2005; 45: 247-268.
  • Wang X, Anadón A, Wu Q, Qiao F, Ares I, Martínez-Larrañaga MR, Yuan Z, Martínez MA. Mechanism of neonicotinoid toxicity: impact on oxidative stress and metabolism. Annu Rev Pharmacol Toxicol. 2018; 58: 471-507.
  • Marfo JT, Fujioka K, Ikenaka Y, Nakayama SM, Mizukawa H, Aoyama Y, Ishizuka M, Taira K. Relationship between urinary N-desmethyl-acetamiprid and typical symptoms including neurological findings: a prevalence case-control study. PLoS One. 2015; 10(11): 1-19.
  • Tasman K, Hidalgo S, Zhu B, Rands SA, Hodge JJ. Neonicotinoids disrupt memory, circadian behaviour and sleep. Sci Rep. 2021; 11(1): 1-13.
  • Terayama H, Endo H, Tsukamoto H, Matsumoto K, Umezu M, Kanazawa T, Ito M, Sato T, Naito M, Kawakami S. Acetamiprid accumulates in different amounts in murine brain regions. Int J Environ Res Public Health. 2016; 13(10): 1-13.
  • Mondal S, Sengupta T, Pradhan S, Hansda R, Mandal P, Tiwari R, Mukhopadhayay S. Impaired learning and memory after a week-long exposure of acetamiprid in adult rats. Adv Anim Vet Sci. 2014; 2(10): 543-548.
  • Kapoor U, Srivastava MK, Bhardwaj S, Srivastava LP. Effect of imidacloprid on antioxidant enzymes and lipid peroxidation in female rats to derive its no observed effect level (NOEL). J Toxicol Sci. 2010; 35(4): 577-581.
  • Gasmi S, Kebieche M, Rouabhi R, Touahria C, Lahouel A, Lakroun Z, Henine S, Soulimani R. 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. 2017; 24(28): 22258-22264.
  • Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci. 2016; 5: 1-13.
  • Williams R, Spencer J, Rice-Evans C. Flavonoids and isoflavones (phytoestrogens): absorption, metabolism, and bioactivity. Free Radic Biol Med. 2004; 36(7): 838-849.
  • Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol. 2008; 585(2-3): 325-337.
  • Rarinca V, Nicoara MN, Ureche D, Ciobica A. Exploitation of quercetin's antioxidative properties in potential alternative therapeutic options for neurodegenerative diseases. Antioxidants (Basel). 2023; 12(7): 1-18.
  • Selvakumar K, Bavithra S, Suganthi M, Benson CS, Elumalai P, Arunkumar R, Krishnamoorthy G, Venkataraman P, Arunakaran J. Protective role of quercetin on PCBs-induced oxidative stress and apoptosis in hippocampus of adult rats. Neurochem Res. 2012; 37(4): 708-721.
  • Fereidouni S, Kumar RR, Chadha VD, Dhawan DK. Quercetin plays protective role in oxidative induced apoptotic events during chronic chlorpyrifos exposure to rats. J Biochem Mol Toxicol. 2019; 33(8): 1-10.
  • Aghababaei F, Hadidi M. Recent advances in potential health benefits of quercetin. Pharmaceuticals (Basel). 2023; 16(7): 1-33.
  • Costa LG, Tait L, de Laat R, Dao K, Giordano G, Pellacani C, Cole TB, Furlong CE. Modulation of paraoxonase 2 (PON2) in mouse brain by the polyphenol quercetin: a mechanism of neuroprotection? Neurochem Res. 2013; 38(9): 1809-1818.
  • Shamsi M, Soodi M, Shahbazi S, Omidi A. Effect of acetamiprid on spatial memory and hippocampal glutamatergic system. Environ Sci Pollut Res Int. 2021; 28(22): 27933-27941.
  • Ghahremani S, Soodi M, Atashi A. Quercetin ameliorates chlorpyrifos-induced oxidative stress in the rat brain: possible involvment of PON2 pathway. J Food Biochem. 2018; Article ID 12530.
  • Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 1984; 11(1): 47-60.
  • Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2006; 1(2): 848-858.
  • Ellman M. A spectrophotometric method for determination of reduced glutathione in tissues. Anal Biochem. 1959; 74(1): 214-226.
  • Beers Jr RF, Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem. 1952; 195(1): 133-140.
  • Jadhav R, Kulkarni YA. Neuroprotective effect of quercetin and memantine against AlCl3-Induced neurotoxicity in albino wistar rats. 2023; 28(1): 1-23.
  • Mohammadi HS, Goudarzi I, Lashkarbolouki T, Abrari K, Elahdadi Salmani M. Chronic administration of quercetin prevent spatial learning and memory deficits provoked by chronic stress in rats. Behav Brain Res. 2014; 270: 196-205.
  • Grewal AK, Singh TG, Sharma D, Sharma V, Singh M, Rahman MH, Najda A, Walasek-Janusz M, Kamel M, Albadrani GM, Akhtar MF, Saleem A, Abdel-Daim MM. Mechanistic insights and perspectives involved in neuroprotective action of quercetin. Biomed Pharmacother. 2021; Article ID 111729.
  • Chiang MC, Tsai TY, Wang CJ. The potential benefits of quercetin for brain health: a review of anti-inflammatory and neuroprotective mechanisms. Int J Mol Sci. 2023; 24(7): 1-16.
  • Dhouib IB, Annabi A, Doghri R, Rejeb I, Dallagi Y, Bdiri Y, Lasram MM, Elgaaied A, Marrakchi R, Fazaa S, Gati A. Neuroprotective effects of curcumin against acetamiprid-induced neurotoxicity and oxidative stress in the developing male rat cerebellum: biochemical, histological, and behavioral changes. Environ Sci Pollut Res Int. 2017; 24(35): 27515-27524.
  • Phogat A, Singh J, Malik V, Kumar V. Neuroprotective potential of berberine against acetamiprid induced toxicity in rats: implication of oxidative stress, mitochondrial alterations, and structural changes in brain regions. J Biochem Mol Toxicol. 2023; Article ID 23434.
  • Zamanian MY, Soltani A, Khodarahmi Z, Alameri AA, Alwan AMR, Ramírez-Coronel AA, Obaid RF, Abosaooda M, Heidari M, Golmohammadi M, Anoush M. Targeting Nrf2 signaling pathway by quercetin in the prevention and treatment of neurological disorders: an overview and update on new developments. Fundam Clin Pharmacol. 2023; 37(6): 1050-1064.
  • Ghazanfari A, Soodi M, Omidi A. Quercetin ameliorates acetamiprid-induced hepatotoxicity and oxidative stress. Physiol Pharmacol. 2021; 25(2): 154-161.
  • Alhusaini A, Fadda LM, Ali HM, Hasan IH, Ali RA, Zakaria EA. Mitigation of acetamiprid– induced renotoxicity by natural antioxidants via the regulation of ICAM, NF-kB and TLR 4 pathways. Pharmacologic Rep. 2019; 71(6): 1088-1094.
  • El-Gendy KS, Aly NM, Mahmoud FH, Allah DA. Toxicological assessment of sublethal dose of acetamiprid in male mice and the efficacy of quercetin. Pestic Biochem Physiol. 2022; Article ID 105078..
  • de Oliveira MR, Nabavi SM, Braidy N, Setzer WN, Ahmed T, Nabavi SF. Quercetin and the mitochondria: a mechanistic view. Biotechnol Adv. 2016; 34(5): 532-549.
  • Gupta R, Shukla RK, Chandravanshi LP, Srivastava P, Dhuriya YK, Shanker J, Singh MP, Pant AB, Khanna VK. Protective role of quercetin in cadmium-induced cholinergic dysfunctions in rat brain by modulating mitochondrial integrity and MAP kinase signaling. Mol Neurobiol. 2017; 54(6): 4560–4583.
  • Harry GJ, D'Hellencourt CL. Dentate gyrus: alterations that occur with hippocampal injury. 2003; 24(3): 343-356.