Modulatory effects of glutathione on oxidative stress disorders induced by imidacloprid in rat brain

Mirjani, Mohammad Sina; Khaksar, Mohammad Reza

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Modulatory effects of glutathione on oxidative stress disorders induced by imidacloprid in rat brain

Mohammad Sina Mirjani

, Mohammad Reza Khaksar ^*

Research Center for Environmental Pollutants, Qom University of Medical Sciences, Qom, Iran , mrkhaksar@muq.ac.ir

Abstract: (344 Views)

Introduction: The widespread use of pesticides, especially neonicotinoid compounds such as imidacloprid, has increased agricultural production but poses serious environmental and neurological threats. Long-term exposure to imidacloprid causes the production of reactive oxygen species, increases lipid peroxidation, and impairs antioxidant and neuronal systems. Glutathione, as an endogenous antioxidant, plays an important protective role in reducing oxidative stress and maintaining neuronal function. The aim of this study was to investigate the effect of L-glutathione intervention in reducing oxidative and neurological disorders caused by short-term exposure to imidacloprid in rats.
Methods: 24 adults male Wistar rats were divided into four groups of 6: Sham group receiving saline, imidacloprid group at a dose of one-tenth of the LD50 (45 mg/kg), glutathione group at a dose of 100 mg/kg, and the combined imidacloprid + glutathione group. All treatments were performed daily for 28 days via gavage. After the end of the period, brain tissue was extracted and oxidative stress indices including lipid peroxidation (MDA), reduced glutathione (GSH) level, total antioxidant capacity (TAC), antioxidant enzyme activities (GPx, GSR, GST, SOD, CAT), and acetylcholinesterase (AChE) activity were measured.
Results: Imidacloprid administration significantly reduced the activities of AChE, TAC, GSH, and GPx, GSR, and GST enzymes, and increased MDA levels and SOD activity (p<0.05). Catalase activity was not affected. L-glutathione intake alone caused a relative increase in TAC and the activities of some antioxidant enzymes. In the combination group, L-glutathione intervention returned most oxidative and neurological indices to levels close to the control group, and a decrease in lipid peroxidation and an increase in antioxidant defense capacity were observed (p<0.01).
Conclusion: The results indicate that short-term exposure to imidacloprid causes oxidative stress and dysfunction in the nervous system. L-glutathione intervention effectively prevents oxidative damage and inhibits the activity of antioxidant enzymes, and modulates AChE activity. These findings confirm the protective role of glutathione in maintaining redox balance and reducing imidacloprid-induced neurotoxicity.

Keywords: Imidacloprid, glutathione, oxidative stress, rat brain

Type of Study: Research | Subject: General
Received: 2026/02/16 | Revised: 2026/06/16 | Accepted: 2026/05/17

References

1. Zhou W, Li M, Achal V. A comprehensive review on environmental and human health impacts of chemical pesticide usage. Emerging Contaminants. 2025;11(1):100410. doi:10.1016/j.emcon.2024.100410

2. Lazarević-Pašti T, Milanković V, Tasić T, Petrović S, Leskovac A. With or Without You?-A Critical Review on Pesticides in Food. Foods. 2025;14(7):1128. doi:10.3390/foods14071128 PMid:40238262 PMCid:PMC11988313

3. Ford KA, Casida JE. Comparative Metabolism and Pharmacokinetics of Seven Neonicotinoid Insecticides in Spinach. J Agric Food Chem. 2008;56(21):10168-75. doi:10.1021/jf8020909 PMid:18922014

4. Jeschke P, Nauen R, Beck ME. Nicotinic Acetylcholine Receptor Agonists: A Milestone for Modern Crop Protection. Angewandte Chemie International Edition. 2013;52(36):9464-85. doi:10.1002/anie.201302550 PMid:23934864

5. Shivanandappa T, Rajashekar Y. Mode of Action of Plant-Derived Natural Insecticides. In: Singh D, editor. Advances in Plant Biopesticides. New Delhi: Springer India; 2014. p. 323-45. doi:10.1007/978-81-322-2006-0_16

6. Zouaoui S, Rouabhi R. Lysosomal disruption, mitochondrial impairment, histopathological and oxidative stress in rat's nervous system after exposure to a neonicotinoid (imidacloprid). Environ Sci Pollut Res Int. 2024;31(49):59472-89. doi:10.1007/s11356-024-35195-5 PMid:39356435

7. Abdelhafez H, Hammam FM, El-Dahshan AA, AboDalam H, Guo J. Imidacloprid Induces Neurotoxicity in Albino Male Rats by Inhibiting Acetylcholinesterase Activity, Altering Antioxidant Status, and Primary DNA Damage. J Toxicol. 2023;2023:4267469. doi:10.1155/2023/4267469 PMid:37727350 PMCid:PMC10506876

8. Mudgal R, Sharma S, Singh S, Ravichandiran V. The neuroprotective effect of ascorbic acid against imidacloprid-induced neurotoxicity and the role of HO-1 in mice. Frontiers in Neurology. 2023; 14: 2023. doi:10.3389/fneur.2023.1130575 PMid:37153653 PMCid:PMC10157196

9. Georgiou-Siafis SK, Tsiftsoglou AS. The Key Role of GSH in Keeping the Redox Balance in Mammalian Cells: Mechanisms and Significance of GSH in Detoxification via Formation of Conjugates. Antioxidants. 2023;12(11):1953. doi:10.3390/antiox12111953 PMid:38001806 PMCid:PMC10669396

10. Labarrere CA, Kassab GS. Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation. Frontiers in Nutrition. 2022; 9: 2022. doi:10.3389/fnut.2022.1007816 PMid:36386929 PMCid:PMC9664149

11. Wang H, Du Ys, Xu Ws, Li Cj, Sun H, Hu Kr, et al. Exogenous glutathione exerts a therapeutic effect in ischemic stroke rats by interacting with intrastriatal dopamine. Acta Pharmacologica Sinica. 2022; 43(3):541-51. doi:10.1038/s41401-021-00650-3 PMid:34035485 PMCid:PMC8888709

12. Mirkovic JJ, Jurinjak Z, Kocic G, Medojevic N, Alexopoulos C. Glutathione as a powerful antioxidant in oxidative stress in the brain tissue of rats caused by the pathophysiological action of copper. Eur Psychiatry. 2021;64(S1):S719-S20. doi:10.1192/j.eurpsy.2021.1906 PMCid:PMC9479844

13. Shri P, Singh KP, Rani V, Nagar DP, Acharya J, Bhaskar ASB. N-acetylcysteine prevents cholinergic and non-cholinergic toxic effects induced by nerve agent poisoning in rats. Toxicol Res (Camb). 2025;14(1):tfae223. doi:10.1093/toxres/tfae223 PMid:39830891 PMCid:PMC11741679

14. Shalaby AA, Hassan ME, Shalaby MB. Protective effects of antioxidant vitamins (C plus E) against oxidative damage induced by the insecticide imidacloprid in male rats. J Med Sci Res. 2022;5(3):33. doi:10.4103/jmisr.jmisr_39_22

15. Ganiyat AM, Caleb OJ, Dezi AD, Adamu M. Glutathione attenuated lambda-cyhalothrin-induced alteration of serum total cholesterol concentration and oxidative stress parameters in rats. Toxicol Res (Camb). 2023;12(1):33-8. doi:10.1093/toxres/tfac080 PMid:36866217 PMCid:PMC9972829

16. Stehle S, Ovcharova V, Wolfram J, Bub S, Herrmann LZ, Petschick LL, et al. Neonicotinoid insecticides in global agricultural surface waters - Exposure, risks and regulatory challenges. Sci Total Environ. 2023;867:161383. doi:10.1016/j.scitotenv.2022.161383PMid:36621497

17. Miller SA, Schmidt TS, Barber LB, Hladik ML, Kolpin DW, Shoda ME, et al. Imidacloprid in United States Rivers, 2013-2022: Persistent Presence and Emerging Chronic Hazard. Environ Sci Technol. 2025;59(49):26702-15. doi:10.1021/acs.est.5c07311 PMid:41344868 PMCid:PMC12713725

18. Xu W, Zhang L, Hou J, Du X, Chen L. Absorption and Distribution of Imidacloprid and Its Metabolites in Goldfish (Carassius auratus Linnaeus). Toxics. 2023;11(7). doi:10.3390/toxics11070619 PMid:37505584 PMCid:PMC10386705

19. Hu X, Zhu S, Chen Y, Zhang L, Tan H, Wu C, et al. Bioaccumulation, Ecotoxicity, and Microbial Responses in Hoplobatrachus rugulosus Tadpoles Following Co-Exposure to Imidacloprid and Microplastics. Animals [Internet]. 2025; 15(13). doi:10.3390/ani15131928 PMid:40646827 PMCid:PMC12249034

20. Sule RO, Condon L, Gomes AV. A Common Feature of Pesticides: Oxidative Stress-The Role of Oxidative Stress in Pesticide-Induced Toxicity. Oxidative Medicine and Cellular Longevity. 2022;2022(1):5563759. doi:10.1155/2022/5563759 PMid:35096268 PMCid:PMC8791758

21. Shadnia S, Dasgar M, Taghikhani S, Mohammadirad A, Khorasani R, Abdollahi M. Protective Effects of alpha-Tocopherol and N-Acetyl-Cysteine on Diazinon-Induced Oxidative Stress and Acetylcholinesterase Inhibition in Rats. Toxicol Mech Methods. 2007;17(2):109-15. doi:10.1080/15376510600860318 PMid:20020979

22. Singh J, Phogat A, Prakash C, Chhikara SK, Singh S, Malik V, et al. N-Acetylcysteine Reverses Monocrotophos Exposure-Induced Hepatic Oxidative Damage via Mitigating Apoptosis, Inflammation and Structural Changes in Rats. Antioxidants. 2022;11(1):90. doi:10.3390/antiox11010090 PMid:35052593 PMCid:PMC8773366

23. Abd-Elhakim YM, Saber TM, Metwally MMM, Abd-Allah NA, Mohamed R, Ahmed GA. Thymol abates the detrimental impacts of imidacloprid on rat brains by lessening oxidative damage and apoptotic and inflammatory reactions. Chem Biol Interact. 2023;383:110690. doi:10.1016/j.cbi.2023.110690 PMid:37648049

24. Xiang X, Wang H, Zhou W, Wang C, Guan P, Xu G, et al. Glutathione Protects against Paraquat-Induced Oxidative Stress by Regulating Intestinal Barrier, Antioxidant Capacity, and CAR Signaling Pathway in Weaned Piglets. Nutrients. 2023;15(1):198. doi:10.3390/nu15010198 PMid:36615853 PMCid:PMC9823711

25. Averill-Bates DA. The antioxidant glutathione. Vitam Horm. 2023;121:109-41. doi:10.1016/bs.vh.2022.09.002

26. Sabbaghziarani F, Soleimani P, Eynshikh FR, Zafari F, Aali E. Reduced ischemia-reperfusion oxidative stress injury by melatonin and N-acetylcysteine in the male rat brain. IBRO Neurosci Rep. 2024;17:131-7. doi:10.1016/j.ibneur.2024.07.004 PMid:39175643 PMCid:PMC11339246

27. Lu H, Zhang DM, Chen HL, Lin YX, Hang CH, Yin HX, et al. N-acetylcysteine suppresses oxidative stress in experimental rats with subarachnoid hemorrhage. J Clin Neurosci. 2009;16(5):684-8. doi:10.1016/j.jocn.2008.04.021 PMid:19264484

28. Yabuki Y, Fukunaga K. Oral administration of glutathione improves memory deficits following transient brain ischemia by reducing brain oxidative stress. Neuroscience. 2013;250:394-407. doi:10.1016/j.neuroscience.2013.07.017 PMid:23872392

29. Garg G, Singh S, Singh AK, Rizvi SI. N-acetyl-l-cysteine attenuates oxidative damage and neurodegeneration in rat brain during aging. Canadian J Physiol Pharmacol. 2018;96(12):1189-96. doi:10.1139/cjpp-2018-0209 PMid:30107137

30. Kanwar SS, Nehru B. Modulatory effects of N-acetylcysteine on cerebral cortex and cerebellum regions of ageing rat brain. Nutr Hosp. 2007;22(1):95-100. PMID: 17260537

31. Hsiao YF, Huang SC, Cheng SB, Hsu CC, Huang YC. Glutathione and Selenium Supplementation Attenuates Liver Injury in Diethylnitrosamine-Induced Hepatocarcinogenic Mice by Enhancing Glutathione-Related Antioxidant Capacities. Int J Mol Sci. 2024;25(21). doi:10.3390/ijms252111339 PMid:39518894 PMCid:PMC11546938

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