Oxidative stress and neuronal dysfunction induced by combined low-dose exposure to abamectin and cypermethrin
Abstract
Background : The increase in agricultural production has been accompanied by intensive pesticide use, leading to chronic environmental contamination. In Togo, residues exceeding regulatory limits have been detected in vegetable crops, particularly abamectin (ABM) and cypermethrin (CYP). ABM, derived from Streptomyces avermitilis, acts on GABA-gated chloride channels and crosses the blood–brain barrier, inducing oxidative stress and neurotoxic damage. CYP, a synthetic pyrethroid, targets voltage-gated sodium channels, resulting in abnormal neuronal discharges and excessive production of reactive oxygen species. While their acute effects are well known, the subchronic impacts of low-dose exposure, especially in combination, remain poorly understood. In this context, the present study aims to evaluate the subchronic neurotoxic effects of combined exposure to abamectin and cypermethrin, administered at realistic doses, in rats.
Methods : This study evaluated the subchronic neurotoxicity of ABM and CYP, administered individually or in combination for 90 days to 40 Wistar rats divided into five groups: control, ABM (0.3 mg/kg/day), CYP (0.7 mg/kg/day), mixture M1 (ABM 0.3 + CYP 0.7 mg/kg/day), and mixture M2 (ABM 0.6 + CYP 1.4 mg/kg/day).
Results : The results revealed that exposure, particularly to mixtures, decreased brain protein levels, significantly reduced glutathione, superoxide dismutase, and catalase, and markedly increased malondialdehyde levels compared to groups exposed to a single pesticide.. Glutathione S-transferase activity was less affected, but caspase-3 was activated in M1 and M2 groups, indicating apoptosis induction. Histological analyses in M1 and M2 groups showed pronounced hypocellularity associated with cellular hypertrophy and necrotic foci compared with controls.
Conclusions : The observed synergistic effect highlights an increased toxicological risk, underscoring the need for further mechanistic studies and appropriate regulatory measures. Under environmental conditions where combined exposures are frequent, these results highlight the importance of considering the impact of mixtures rather than isolated compounds.
Keywords: Abamectin, Cypermethrin, Oxidative stress, Pesticide mixture, low-dose
Keywords:
Abamectin, Cypermethrin, Pesticide mixtureDOI
https://doi.org/10.22270/jddt.v16i1.7534References
1. Khan BA, Nadeem MA, Nawaz H, Amin MM, Abbasi GH, Nadeem M, et al. Pesticides: Impacts on Agriculture Productivity, Environment, and Management Strategies. In: Aftab T, éditeur. Emerging Contaminants and Plants [Internet]. Cham: Springer International Publishing; 2023 [cité 30 oct 2025]. p. 109 34. (Emerging Contaminants and Associated Treatment Technologies). https://doi.org/10.1007/978-3-031-22269-6_5
2. Garraway JL. Insecticides, Fungicides and Herbicides. In: Biotechnology-the Science and the Business [Internet]. CRC Press; 2020 [cité 30 oct 2025]. p. 497 514. Disponible sur: https://www.taylorfrancis.com/chapters/edit/10.1201/9781003078432-24/insecticides-fungicides-herbicides-james-garraway https://doi.org/10.1201/9781003078432-24
3. Gianessi LP. The increasing importance of herbicides in worldwide crop production. Pest Manag Sci. oct 2013;69(10):1099 105. https://doi.org/10.1002/ps.3598 PMid:23794176
4. Yadav A, Tandon A, Seth B, Goyal S, Singh SJ, Tiwari SK, et al. Cypermethrin Impairs Hippocampal Neurogenesis and Cognitive Functions by Altering Neural Fate Decisions in the Rat Brain. Mol Neurobiol. janv 2021;58(1):263 80. https://doi.org/10.1007/s12035-020-02108-9 PMid:32920670
5. Carvalho FP. Pesticides, environment, and food safety. Food Energy Secur. mai 2017;6(2):48 60. https://doi.org/10.1002/fes3.108
6. Gavrilescu M. Fate of Pesticides in the Environment and its Bioremediation. Eng Life Sci. déc 2005;5(6):497 526. https://doi.org/10.1002/elsc.200520098
7. Ghasemnejad-Berenji M, Nemati M, Pourheydar B, Gholizadeh S, Karimipour M, Mohebbi I, et al. Neurological effects of long-term exposure to low doses of pesticides mixtures in male rats: Biochemical, histological, and neurobehavioral evaluations. Chemosphere. 2021;264:128464. https://doi.org/10.1016/j.chemosphere.2020.128464 PMid:33049502
8. Eddleston M. Poisoning by pesticides. Medicine (Baltimore). 2020;48(3):214 7. https://doi.org/10.1016/j.mpmed.2019.12.019
9. Singh NS, Sharma R, Parween T, Patanjali PK. Pesticide Contamination and Human Health Risk Factor. In: Oves M, Zain Khan M, M.I. Ismail I, éditeurs. Modern Age Environmental Problems and their Remediation [Internet]. Cham: Springer International Publishing; 2018 [cité 30 oct 2025]. p. 49 68. https://doi.org/10.1007/978-3-319-64501-8_3
10. Grewal AS. Pesticide Residues in Food Grains, Vegetables, and Fruits: A Hazard to Human Health.(2017) J Med ChemToxicol 2 (1): 1-7. J Med Chem Toxicol [Internet]. 2017 [cité 30 oct 2025];2(1). Disponible sur: https://gcwgandhinagar.com/econtent/document/1587965466Pesticide-Residues-in-FoodGrains-Vegetables-and-Fruits-A-Hazard-to-Human-Health.pdf
11. Mensah AA, Mawussi G, Karou SD. Gestion des pesticides sur les perimetres maraichers de la Zone Cotiere du Togo. J Rech Sci L'Université Lomé. 15 nov 2021;23(2):11 25.
12. Diallo A, Zotchi K, Lawson-evi P, Bakoma B, Badjabaissi E, Kwashie EG. Pesticides Use Practice by Market Gardeners in Lome (Togo). J Toxicol. 22 sept 2020;2020:1 5. https://doi.org/10.1155/2020/8831873 PMid:33029138 PMCid:PMC7528109
13. Badjabaissi E, Aboudoulatif D, Assiki T, Dossou-Yovo K, Assih M, Sanvee S, et al. Analysis of Pesticide Residues in Lomé Vegetables: Implications for Health and Food Consumption. J Pharmacol Toxicol. 15 janv 2024;19:13 26. https://doi.org/10.3923/jpt.2024.13.26
14. Hossam El Din HA, Abdallah AA, Abdel-Razik RK, Hamed NA, Elshatory A, Awad W, et al. Sex comparison of oxidative stress, mitochondrial dysfunction, and apoptosis triggers induced by single-dose Abamectin in albino rats. Pestic Biochem Physiol. 2024;201:105903. https://doi.org/10.1016/j.pestbp.2024.105903 PMid:38685225
15. Adiguzel C, Karaboduk H, Uzunhisarcikli M. Protective role of melatonin against abamectin-induced biochemical, immunohistochemical, and ultrastructural alterations in the testicular tissues of rats. Microsc Microanal. 2024;30(5):962 77. https://doi.org/10.1093/mam/ozae080 PMid:39189879
16. Ismail T, Ahmad SN, Ahmad KR, Suleman S, Sitara S, Kanwal MA, et al. Cypermethrin (CYP) and lambda-cyhalothrin (λ-CYH) exposure induced histopathological defects of reproductive organs in pregnant mice. Fluoride. 2023;56:488 502.
17. Kathim AS, Al-Aitte S. Cypermethrin insecticide induced histopathological alteration in testis and ovary of males and female mice. Tex J Agric Biol Sci. 2022;6:10 7.
18. Kotb GA, Ziada RM, Farag AAG. Acute Abamectin exposure induces oxidative stress responses in liver of male albino rats. Egypt Acad J Biol Sci F Toxicol Pest Control. 2021;13(1):71 81. https://doi.org/10.21608/eajbsf.2021.142524
19. Alalwani AD. Nephrotoxicity of cypermethrin in rats. Histopathological aspects. Histol Histopathol. 2020;35(12):1437 48.
20. Moqbel FS, Al-Eryani MA, Abd Al Galil FM. Histopathological and biochemical effects of abamectin on kidney in male albino rats. J Entomol Zool Stud. 2017;5:245 9.
21. Jaafer NS, Rabee AM. Effect of Cypermethrin on Hematological and Histological Parameters in Male Albino Mice | Ibn AL-Haitham Journal For Pure and Applied Sciences. Ibn AL-Haitham J Pure Appl Sci. 2025;38(3):68 78. https://doi.org/10.30526/38.3.3481
22. Tavakkoli M, Dadkhah M, Saadati H, Afshari S, Mostafalou S. Neurobehavioral toxicity of cypermethrin in association with oxidative, inflammatory and neurotrophic changes in the hippocampus of rats. Int J Environ Health Res. 8 mai 2025;1 12. https://doi.org/10.1080/09603123.2025.2503472 PMid:40338169
23. Ibrahim KA, Eleyan M, Khwanes SA, Mohamed RA, Ayesh BM. Alpha-mangostin attenuates the apoptotic pathway of abamectin in the fetal rats' brain by targeting pro-oxidant stimulus, catecholaminergic neurotransmitters, and transcriptional regulation of reelin and nestin. Drug Chem Toxicol. 2 nov 2022;45(6):2496 508. https://doi.org/10.1080/01480545.2021.1960856 PMid:34338122
24. Ahmad L, Gul ST, Saleemi MK, Hussain R, Naqvi SNH, Du X xia, et al. The effect of different repeated doses of cypermethrin on the behavioral and histological alterations in the brain of rabbits (Oryctolagus cuniculi). 2021 [cité 30 oct 2025]; https://www.academia.edu/download/87290397/IJVS_2021_10_347_354.pdf https://doi.org/10.47278/journal.ijvs/2021.092 PMid:34776615
25. Radi AM, Mohammed ET, Abushouk AI, Aleya L, Abdel-Daim MM. The effects of abamectin on oxidative stress and gene expression in rat liver and brain tissues: Modulation by sesame oil and ascorbic acid. Sci Total Environ. janv 2020;701:134882. https://doi.org/10.1016/j.scitotenv.2019.134882 PMid:31739238
26. Woodward KN. GABAergic Neurotransmission and Toxicity 2: Macrocyclic Lactones. 2024 [cité 30 oct 2025]; Disponible sur: https://books.rsc.org/books/edited-volume/2189/chapter/7986729 https://doi.org/10.1039/9781839165795-00179
27. Gur C, Kandemir O, Kandemir FM. Investigation of the effects of hesperidin administration on abamectin‐induced testicular toxicity in rats through oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, autophagy, and JAK2 / STAT3 pathways. Environ Toxicol. mars 2022;37(3):401 12. https://doi.org/10.1002/tox.23406 PMid:34748272
28. Hong Y, Huang Y, Yang X, Zhang J, Li L, Huang Q, et al. Abamectin at environmentally-realistic concentrations cause oxidative stress and genotoxic damage in juvenile fish (Schizothorax prenanti). Aquat Toxicol. 2020;225:105528. https://doi.org/10.1016/j.aquatox.2020.105528 PMid:32569996
29. Celik-Ozenci C, Tasatargil A, Tekcan M, Sati L, Gungor E, Isbir M, et al. Effects of abamectin exposure on male fertility in rats: potential role of oxidative stress-mediated poly (ADP-ribose) polymerase (PARP) activation. Regul Toxicol Pharmacol. 2011;61(3):310 7. https://doi.org/10.1016/j.yrtph.2011.09.001 PMid:21945325
30. Liang Y, Dong B, Pang N, Hu J. ROS generation and DNA damage contribute to abamectin-induced cytotoxicity in mouse macrophage cells. Chemosphere. 1 nov 2019;234:328 37. https://doi.org/10.1016/j.chemosphere.2019.06.031 PMid:31229705
31. BUG TG. Pests and pest control. Cent Excell Mar Biol Univ Karachi Karachi [Internet]. 2015 [cité 30 oct 2025];126. Disponible sur: https://www.zsp.com.pk/PRO2015.pdf#page=161
32. Kweon J, Lim W, Lee H, Kim J, Song G, Jeong W, et al. Cypermethrin triggers oxidative stress, apoptosis, and inflammation in bovine mammary glands by disruption of mitogen-activated protein kinase (MAPK) pathways and calcium homeostasis. Reprod Toxicol. 2025;132:108842. https://doi.org/10.1016/j.reprotox.2025.108842 PMid:39884399
33. Zhao Y, Ye X, Xiong Z, Ihsan A, Ares I, Martínez M, et al. Cancer metabolism: the role of ROS in DNA damage and induction of apoptosis in cancer cells. Metabolites. 2023;13(7):796. https://doi.org/10.3390/metabo13070796 PMid:37512503 PMCid:PMC10383295
34. Sule RO, Condon L, Gomes AV. A Common Feature of Pesticides: Oxidative Stress-The Role of Oxidative Stress in Pesticide‐Induced Toxicity. Zhou X, éditeur. Oxid Med Cell Longev. janv 2022;2022(1):5563759. https://doi.org/10.1155/2022/5563759 PMid:35096268 PMCid:PMC8791758
35. Jabłońska-Trypuć A. Pesticides as inducers of oxidative stress. React Oxyg Species. 2017;3(8):96 110. https://doi.org/10.20455/ros.2017.823
36. Eskenazi B, Rosas LG, Marks AR, Bradman A, Harley K, Holland N, et al. Pesticide Toxicity and the Developing Brain. Basic Clin Pharmacol Toxicol. févr 2008;102(2):228 36. PMid:18226078 https://doi.org/10.1111/j.1742-7843.2007.00171.x
37. Modgil S, Lahiri DK, Sharma VL, Anand A. Role of early life exposure and environment on neurodegeneration: implications on brain disorders. Transl Neurodegener. déc 2014;3(1):9. https://doi.org/10.1186/2047-9158-3-9 PMid:24847438 PMCid:PMC4028099
38. Borgert CJ, Quill TF, McCarty LS, Mason AM. Can mode of action predict mixture toxicity for risk assessment? Toxicol Appl Pharmacol. 2004;201(2):85 96. https://doi.org/10.1016/j.taap.2004.05.005 PMid:15541748
39. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72(1 2):248 54. https://doi.org/10.1006/abio.1976.9999 PMid:942051
40. Patlolla AK, Barnes C, Yedjou C, Velma VR, Tchounwou PB. Oxidative stress, DNA damage, and antioxidant enzyme activity induced by hexavalent chromium in Sprague‐Dawley rats. Environ Toxicol. févr 2009;24(1):66 73. https://doi.org/10.1002/tox.20395 PMid:18508361 PMCid:PMC2769560
41. Sedlak J, Lindsay HR. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968;25:192 205. https://doi.org/10.1016/0003-2697(68)90092-4 PMid:4973948
42. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249(22):7130 9. https://doi.org/10.1016/S0021-9258(19)42083-8 PMid:4436300
43. Aebi H. [13] Catalase in vitro. In: Methods in enzymology [Internet]. Elsevier; 1984 [cité 30 oct 2025]. p. 121 6. Disponible sur: https://www.sciencedirect.com/science/article/pii/S0076687984050163 https://doi.org/10.1016/S0076-6879(84)05016-3 PMid:6727660
44. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974;47(3):469 74. https://doi.org/10.1111/j.1432-1033.1974.tb03714.x PMid:4215654
45. Hassan I, Chibber S, Khan AA, Naseem I. Cisplatin-Induced Neurotoxicity In Vivo Can Be Alleviated by Riboflavin Under Photoillumination. Cancer Biother Radiopharm. mars 2013;28(2):160 8. https://doi.org/10.1089/cbr.2012.1312 PMid:23215961
46. Baldi I, Cordier S, Coumoul X, Elbaz A, Gamet-Payrastre L, Lebailly P, et al. Pesticides: Effets sur la santé [Doctoral dissertation, Institut national de la santé et de la recherche médicale]. INSERM; 2013.
47. Slotkin TA, Tate CA, Ryde IT, Levin ED, Seidler FJ. Organophosphate Insecticides Target the Serotonergic System in Developing Rat Brain Regions: Disparate Effects of Diazinon and Parathion at Doses Spanning the Threshold for Cholinesterase Inhibition. Environ Health Perspect. oct 2006;114(10):1542 6. https://doi.org/10.1289/ehp.9337 PMid:17035140 PMCid:PMC1626396
48. Feoli AM, Siqueira IR, Almeida L, Tramontina AC, Vanzella C, Sbaraini S, et al. Effects of protein malnutrition on oxidative status in rat brain. Nutrition. 2006;22(2):160 5. https://doi.org/10.1016/j.nut.2005.06.007 PMid:16459228
49. Mayne ST. Antioxidant Nutrients and Chronic Disease: Use of Biomarkers of Exposure and Oxidative Stress Status in Epidemiologic Research. J Nutr. 1 mars 2003;133(3):933S-940S. https://doi.org/10.1093/jn/133.3.933S PMid:12612179
50. Stegeman JJ, Brouwer B, Di Giulio RT, Lars F, Fowler BA, Sanders BM, et al. Molecular responses to environmental contamination: enzyme and protein systems as indicators of chemical exposure and effect. In: Molecular responses to environmental contamination: enzyme and protein systems as indicators of chemical exposure and effect. CRC Press; 2018. p. 235 336. (In Biomarkers). https://doi.org/10.1201/9781351070270-7 PMid:29503637 PMCid:PMC5820305
51. Meredith SC. Protein Denaturation and Aggregation: Cellular Responses to Denatured and Aggregated Proteins. Ann N Y Acad Sci. mars 2006;1066(1):181 221. https://doi.org/10.1196/annals.1363.030 PMid:16533927
52. Yang L, Chen JH, Xu T, Zhou AS, Yang HK. Rice protein improves oxidative stress by regulating glutathione metabolism and attenuating oxidative damage to lipids and proteins in rats. Life Sci. 2012;91(11 12):389 94. https://doi.org/10.1016/j.lfs.2012.08.003 PMid:22906634
53. Tauffenberger A, Magistretti PJ. Reactive Oxygen Species: Beyond Their Reactive Behavior. Neurochem Res. janv 2021;46(1):77 87. https://doi.org/10.1007/s11064-020-03208-7 PMid:33439432 PMCid:PMC7829243
54. Mailloux RJ. An Update on Mitochondrial Reactive Oxygen Species Production. Antioxidants. juin 2020;9(6):472. https://doi.org/10.3390/antiox9060472 PMid:32498250 PMCid:PMC7346187
55. Wang X, Martínez MA, Dai M, Chen D, Ares I, Romero A, et al. Permethrin-induced oxidative stress and toxicity and metabolism. A review. Environ Res. 2016;149:86 104. https://doi.org/10.1016/j.envres.2016.05.003 PMid:27183507
56. Bhardwaj JK, Mittal M, Saraf P, Kumari P. Pesticides induced oxidative stress and female infertility: a review. Toxin Rev. 2 janv 2020;39(1):1 13. https://doi.org/10.1080/15569543.2018.1474926
57. Aoun M, Tiranti V. Mitochondria: a crossroads for lipid metabolism defect in neurodegeneration with brain iron accumulation diseases. Int J Biochem Cell Biol. 2015;63:25 31. https://doi.org/10.1016/j.biocel.2015.01.018 PMid:25668476
58. 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. PMid:38001806 PMCid:PMC10669396 https://doi.org/10.3390/antiox12111953
59. Rjeibi I, Ben Saad A, Hfaiedh N. Oxidative damage and hepatotoxicity associated with deltamethrin in rats: The protective effects of Amaranthus spinosus seed extract. Biomed Pharmacother. 1 déc 2016;84:853 60. https://doi.org/10.1016/j.biopha.2016.10.010 PMid:27728895
60. Raj Rai S, Bhattacharyya C, Sarkar A, Chakraborty S, Sircar E, Dutta S, et al. Glutathione: Role in Oxidative/Nitrosative Stress, Antioxidant Defense, and Treatments. ChemistrySelect. 14 mai 2021;6(18):4566 90. https://doi.org/10.1002/slct.202100773
61. Bekkairi S, Bouchiha H, Gasmi S, Rouabhi R, Boualleg O. Abamectin-induced neurotoxicity and preventive effect of Ephedra essential oils against this toxicity in rats. Stud Eng Exact Sci. 2024;5(3):e12359 e12359. https://doi.org/10.54021/seesv5n3-004
62. Sharma P, Firdous S, Singh R. Neurotoxic effect of cypermethrin and protective role of resveratrol in Wistar rats. Int J Nutr Pharmacol Neurol Dis. 2014;4(2):104. https://doi.org/10.4103/2231-0738.129598
63. Vaish S, Gupta D, Mehrotra R, Mehrotra S, Basantani MK. Glutathione S-transferase: a versatile protein family. 3 Biotech. juill 2020;10(7):321. https://doi.org/10.1007/s13205-020-02312-3 PMid:32656054 PMCid:PMC7320970
64. Sauer E, Moro AM, Brucker N, Nascimento S, Gauer B, Fracasso R, et al. Liver δ-Aminolevulinate Dehydratase Activity is Inhibited by Neonicotinoids and Restored by Antioxidant Agents. Int J Environ Res Public Health. nov 2014;11(11):11676 90. https://doi.org/10.3390/ijerph111111676 PMid:25402564 PMCid:PMC4245637
65. Board PG, Menon D. Glutathione transferases, regulators of cellular metabolism and physiology. Biochim Biophys Acta Bba-Gen Subj. 2013;1830(5):3267 88. https://doi.org/10.1016/j.bbagen.2012.11.019 PMid:23201197
66. Ademi M. CATALASE ACTIVITY IN INTERACTION WITH IONIZED WATER AND OTHER ANTIOXIDANTS IN BLOOD PLASMA, LIVER, AND KIDNEY OF THE RAT DURING HYPERTHERMIC STRESS. MEDIS - Int J Med Sci Res. 14 déc 2022;1:21 5. https://doi.org/10.35120/medisij010421a
67. Madkour L. Citation: Loutfy H Madkour. Function of Reactive Oxygen Species (ROS) Inside the Living Organisms and Sources of Oxidants Function of Reactive Oxygen Species (ROS) Inside the Living Organisms and Sources of Oxidants. J Glob Pharma Technol. 3 juill 2019;2:1 23.
68. Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex J Med. 2018;54(4):287 93. https://doi.org/10.1016/j.ajme.2017.09.001
69. Ileriturk M, Kandemir O, Kandemir FM. Evaluation of protective effects of quercetin against cypermethrin‐induced lung toxicity in rats via oxidative stress, inflammation, apoptosis, autophagy, and endoplasmic reticulum stress pathway. Environ Toxicol. nov 2022;37(11):2639 50. https://doi.org/10.1002/tox.23624 PMid:35876585
70. Abd El-Moneim Ibrahim K, Mohamed Abdelrahman S, K. A. Elhakim H, Ali Ragab E. Single or combined exposure to chlorpyrifos and cypermethrin provoke oxidative stress and downregulation in monoamine oxidase and acetylcholinesterase gene expression of the rat's brain. Environ Sci Pollut Res. avr 2020;27(11):12692 703. https://doi.org/10.1007/s11356-020-07864-8 PMid:32006337
71. Adegbesan BO, Adenuga GA. Effect of lead exposure on liver lipid peroxidative and antioxidant defense systems of protein-undernourished rats. Biol Trace Elem Res. mai 2007;116(2):219 25. https://doi.org/10.1007/s12011-007-9029-8 PMid:17646689
72. Yekti R, Bukhari A, Jafar N, Thaha AR. Measurement of malondialdehyde (MDA) as a good indicator of lipid peroxidation. Int J Allied Med Sci Clin Res IJAMSCR. 2018;6(4):1 3.
73. Valgimigli L. Lipid peroxidation and antioxidant protection. Biomolecules. 2023;13(9):1291. PMid:37759691 PMCid:PMC10526874 https://doi.org/10.3390/biom13091291
74. Alsemeh A, AbdelRahman M, Mahmoud F, Abd El Fattah E. Neurotoxicity of Cypermethrin on Rat Cerebral Cortex and the Alleviated effect of Hydroxytyrosol. J Med Histol. 2020;4(2):214 36. https://doi.org/10.21608/jmh.2021.54223.1087
75. Ali HF. Cellular Mechanism involved in cypermethrin induced neurotoxicity. Rec Pharm Biomed Sci. 2020;4(1):32 9. https://doi.org/10.21608/rpbs.2019.17969.1043
76. Wang B, Wang Y, Zhang J, Hu C, Jiang J, Li Y, et al. ROS-induced lipid peroxidation modulates cell death outcome: mechanisms behind apoptosis, autophagy, and ferroptosis. Arch Toxicol. juin 2023;97(6):1439 51. https://doi.org/10.1007/s00204-023-03476-6 PMid:37127681
77. Bayır H, Anthonymuthu TS, Tyurina YY, Patel SJ, Amoscato AA, Lamade AM, et al. Achieving life through death: redox biology of lipid peroxidation in ferroptosis. Cell Chem Biol. 2020;27(4):387 408. https://doi.org/10.1016/j.chembiol.2020.03.014 PMid:32275865 PMCid:PMC7218794
78. Gęgotek A, Skrzydlewska E. Biological effect of protein modifications by lipid peroxidation products. Chem Phys Lipids. 2019;221:46 52. PMid:30922835 https://doi.org/10.1016/j.chemphyslip.2019.03.011
79. Abramov AY, Potapova EV, Dremin VV, Dunaev AV. Interaction of oxidative stress and misfolded proteins in the mechanism of neurodegeneration. Life. 2020;10(7):101. https://doi.org/10.3390/life10070101 PMid:32629809 PMCid:PMC7400128
80. Gandhi S, Abramov AY. Mechanism of Oxidative Stress in Neurodegeneration. Oxid Med Cell Longev. 2012;2012:1 11. https://doi.org/10.1155/2012/428010 PMid:22685618 PMCid:PMC3362933
81. Boudefar S, Sayoud A. Etude de la neurotoxicité liée au stress oxydant induit par les pyréthrinoides chez le rat wistar. [PhD Thesis]. université de jijel; 2017.
82. Abdel-Razik RK, Hamed NA. Deleterious effect of abamectin on rat brain mitochondria. Alex Sci Exch J. 2015;36(OCTOBER-DECEMBER):423 8. https://doi.org/10.21608/asejaiqjsae.2015.2964
83. DiMauro S, Schon EA. Mitochondrial Disorders in the Nervous System. Annu Rev Neurosci. 1 juill 2008;31(1):91 123. https://doi.org/10.1146/annurev.neuro.30.051606.094302 PMid:18333761
84. Sarailoo M, Afshari S, Asghariazar V, Safarzadeh E, Dadkhah M. Cognitive Impairment and Neurodegenerative Diseases Development Associated with Organophosphate Pesticides Exposure: a Review Study. Neurotox Res. oct 2022;40(5):1624 43. https://doi.org/10.1007/s12640-022-00552-0 PMid:36066747
85. Rodrigues JA, Narasimhamurthy RK, Joshi MB, Dsouza HS, Mumbrekar KD. Pesticides Exposure-Induced Changes in Brain Metabolome: Implications in the Pathogenesis of Neurodegenerative Disorders. Neurotox Res. oct 2022;40(5):1539 52. https://doi.org/10.1007/s12640-022-00534-2 PMid:35781222 PMCid:PMC9515138
86. Ghosh N, Das A, Chaffee S, Roy S, Sen CK. Reactive oxygen species, oxidative damage and cell death. In: Immunity and inflammation in health and disease [Internet]. Elsevier; 2018 [cité 30 oct 2025]. p. 45 55. https://www.sciencedirect.com/science/article/pii/B9780128054178000044 https://doi.org/10.1016/B978-0-12-805417-8.00004-4
87. Obeng E. Apoptosis (programmed cell death) and its signals - A review. Braz J Biol. 2021;81:1133 43. https://doi.org/10.1590/1519-6984.228437 PMid:33111928
88. Nagata S, Tanaka M. Programmed cell death and the immune system. Nat Rev Immunol. mai 2017;17(5):333 40. https://doi.org/10.1038/nri.2016.153 PMid:28163302
89. Chipuk JE, Green DR. Do inducers of apoptosis trigger caspase-independent cell death? Nat Rev Mol Cell Biol. 2005;6(3):268 75. https://doi.org/10.1038/nrm1573 PMid:15714200
90. Kumar V, Sami N, Kashav T, Islam A, Ahmad F, Hassan MI. Protein aggregation and neurodegenerative diseases: From theory to therapy. Eur J Med Chem. 29 nov 2016;124:1105 20. https://doi.org/10.1016/j.ejmech.2016.07.054 PMid:27486076
91. Borza LR. A review on the cause-effect relationship between oxidative stress and toxic proteins in the pathogenesis of neurodegenerative diseases. Med-Surg J. 2014;118(1):19 27.
92. Alqahtani T, Deore SL, Kide AA, Shende BA, Sharma R, Chakole RD, et al. Mitochondrial dysfunction and oxidative stress in Alzheimer's disease, and Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis-an updated review. Mitochondrion. 2023;71:83 92. https://doi.org/10.1016/j.mito.2023.05.007 PMid:37269968
93. Erekat NS. Apoptosis and its therapeutic implications in neurodegenerative diseases. Clin Anat. janv 2022;35(1):65 78. https://doi.org/10.1002/ca.23792 PMid:34558138
94. Herawati IE, Lesmana R, Levita J, Subarnas A. Molecular interaction of ricin-a with caspase-3, caspase-8, caspase-9 and autophagy-related gene5 (ATG5) to understand its role as anticancer agent. Chem. 2021;14(3):1790 4. https://doi.org/10.31788/RJC.2021.1436298
95. Morris G, Berk M. The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Med. déc 2015;13(1):68. https://doi.org/10.1186/s12916-015-0310-y PMid:25889215 PMCid:PMC4382850
96. Unnisa A, Greig NH, Kamal MA. Inhibition of Caspase 3 and Caspase 9 Mediated Apoptosis: A MultimodalTherapeutic Target in Traumatic Brain Injury. Curr Neuropharmacol. avr 2023;21(4):1001 12. https://doi.org/10.2174/1570159X20666220327222921 PMid:35339178 PMCid:PMC10227914
97. Muhammed RE, El-Desouky MA, Abo-Seda SB, Nahas AA, Elhakim HKA, Alkhalaf MI. The protecting role of Moringa oleifera in cypermethrin-induced mitochondrial dysfunction and apoptotic events in rats brain. J King Saud Univ - Sci. sept 2020;32(6):2717 22. https://doi.org/10.1016/j.jksus.2020.06.006
98. Hussien HM, Abdou HM, Yousef MI. Cypermethrin induced damage in genomic DNA and histopathological changes in brain and haematotoxicity in rats: the protective effect of sesame oil. Brain Res Bull. 2013;92:76 83. https://doi.org/10.1016/j.brainresbull.2011.10.020 PMid:22085743
99. Ashafaq M, Hussain S, Alshahrani S, Siddiqui R, Alam MI, Elhassan Taha MM, et al. Neuroprotective effects of nano-curcumin against cypermethrin associated oxidative stress and up-regulation of apoptotic and inflammatory gene expression in rat brains. Antioxidants. 2023;12(3):644. https://doi.org/10.3390/antiox12030644 PMid:36978892 PMCid:PMC10045852
100. Strasser A, Vaux DL. Cell death in the origin and treatment of cancer. Mol Cell. 2020;78(6):1045 54. https://doi.org/10.1016/j.molcel.2020.05.014 PMid:32516599
101. Labi V, Erlacher M. How cell death shapes cancer. Cell Death Dis. 5 mars 2015;6(3):e1675 e1675. https://doi.org/10.1038/cddis.2015.20 PMid:25741600 PMCid:PMC4385913
102. Nervous System | 22 | v2 | Toxicologic Pathology | Mark T. Butt, Alys [Internet]. [cité 30 oct 2025]. Disponible sur: https://www.taylorfrancis.com/chapters/edit/10.1201/9780429504624-22/nervous-system-mark-butt-alys-bradley-robert-sills
103. Vinters HV, Kleinschmidt-DeMasters BK. General pathology of the central nervous system. In: Greenfield's Neuropathology-Two Volume Set [Internet]. CRC Press; 2018 [cité 30 oct 2025]. p. 25 82. https://www.taylorfrancis.com/chapters/edit/10.1201/9781315382715-6/general-pathology-central-nervous-system-harry-vinters-bk-kleinschmidt-demasters https://doi.org/10.1201/9781315382715-6 PMid:29124544
104. Astiz M, De Alaniz MJ, Marra CA. Effect of pesticides on cell survival in liver and brain rat tissues. Ecotoxicol Environ Saf. 2009;72(7):2025 32. https://doi.org/10.1016/j.ecoenv.2009.05.001 PMid:19493570
105. Chalimoniuk M, Jagsz S, Sadowska-Krepa E, Chrapusta SJ, Klapcinska B, Langfort J. Diversity of endurance training effects on antioxidant defenses and oxidative damage in different brain regions of adolescent male rats. J Physiol Pharmacol. 2015;66(4):539 47.
106. Mohamadin AM, Sheikh B, Abd El-Aal AA, Elberry AA, Al-Abbasi FA. Protective effects of Nigella sativa oil on propoxur-induced toxicity and oxidative stress in rat brain regions. Pestic Biochem Physiol. 2010;98(1):128 34. https://doi.org/10.1016/j.pestbp.2010.05.011
107. Fujikawa DG. The role of excitotoxic programmed necrosis in acute brain injury. Comput Struct Biotechnol J. 2015;13:212 21. https://doi.org/10.1016/j.csbj.2015.03.004 PMid:25893083 PMCid:PMC4398818
108. Xiong K, Liao H, Long L, Ding Y, Huang J, Yan J. Necroptosis contributes to methamphetamine-induced cytotoxicity in rat cortical neurons. Toxicol In Vitro. 2016;35:163 8. https://doi.org/10.1016/j.tiv.2016.06.002 PMid:27288563
109. Sharma D, Sangha GK. Triazophos induced neuro-splenic toxicity and evaluation of antioxidative potential of aqueous Broccoli extract in Wistar albino rats. J Appl Nat Sci. 2021;13(2):616. https://doi.org/10.31018/jans.v13i2.2644
110. Syed F, Chandravanshi LP, Khanna VK, Soni I. Beta-cyfluthrin induced neurobehavioral impairments in adult rats. Chem Biol Interact. 2016;243:19 28. https://doi.org/10.1016/j.cbi.2015.11.015 PMid:2660415
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Copyright (c) 2026 Essotolom Badjabaissi, Sabrina Chris Janiba Sanvee, Yendubé T. Kantati, Komlan Mawubédjro Dossou-Yovo, Mindédé Assih, Tchare Assiki, Toukilnan Djiwa, Batomayena Bakoma, Aboudoulatif Diallo
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