Cellular and subcellular effects of chronic low-dose Lambda-cyhalothrin pesticide exposure modulated by medicinal plant methanol extract in rat
Abstract
The extensive use of Lambda-cyhalothrin (LCT) has been associated with the various toxicities that non-target organisms can undergo including mammals. However, the mechanism of LCT-induced cytotoxicity in animal brain cells is still elusive, particularly in brain regions, notably the hippocampus, an area directly involved in cognitive function. This study aimed to investigate the neurotoxic effects in the rat hippocampus chronically exposed to LCT (0.18 mg/kg and 0.36 mg/kg), and the neuroprotective potential of Melissa officinalis L methanol extract (MOE) (200 mg/kg) against this toxicity. After experimental period (90 days), the redox status, the functional and structural integrity of the hippocampus mitochondria as well as the apoptotic signaling pathway were evaluated. The current findings suggest that LCT induces an imbalance of mitochondrial redox status characterized by, on one side, an increase of stress markers such as protein carbonyls (PCO), malondialdehyde (MDA), and hydrogen peroxide (H2O2) levels; and on the other side, a decline in the potential of antioxidant systems, namely the level of mitochondrial enzymatic activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione (GSH).This study also showed an increase in mitochondrial permeability, along with mitochondrial edema and considerable decrease in its O2 consumption. Moreover, the same results recorded an increase in caspase-3 and cytosolic cytochrome-c. Conversely, this study proved that all these toxic aspects induced by LCT were significantly mitigated when the administration of this synthetic pyrethroid was associated with MOE. Taken together, data of this study shed light on mitochondrial damage and apoptosis stimulation under the toxic effect of LCT and suggests that MOE is endowed with potent neuroprotective effects, possibly via its antioxidant and antiapoptotic properties.
References
1. Dar SA, Mir SH, Wani SH, et al. Insect Pest Management in Organic Agriculture—A Fast Growing Approach of 21st Century. International Journal of Agriculture, Environment and Sustainability. 2021; 3: 1-6.
2. El Bouzaidi H, Hafiane FZ, Fekhaoui M. Inventory of Pesticides and their impact on the environment by calculating the frequency of treatment indicator in the Gharb plain (Morocco). Mediterranean Journal of Chemistry. 2020; 10(4): 406. doi: 10.13171/mjc10402005041137fzh
3. Neuwirthová N, Trojan M, Svobodová M, et al. Pesticide residues remaining in soils from previous growing season(s)—Can they accumulate in non-target organisms and contaminate the food web? Science of The Total Environment. 2019; 646: 1056-1062. doi: 10.1016/j.scitotenv.2018.07.357
4. El‐Bialy BES, Abd Eldaim MA, Hassan A, et al. Ginseng aqueous extract ameliorates lambda‐cyhalothrin‐acetamiprid insecticide mixture for hepatorenal toxicity in rats: Role of oxidative stress‐mediated proinflammatory and proapoptotic protein expressions. Environmental Toxicology. 2019; 35(2): 124-135. doi: 10.1002/tox.22848
5. Ravula AR, Yenugu S. Long term oral administration of a mixture of pyrethroids affects reproductive function in rats. Reproductive Toxicology. 2019; 89: 1-12. doi: 10.1016/j.reprotox.2019.06.007
6. Chang J, Hao W, Xu Y, et al. Stereoselective degradation and thyroid endocrine disruption of lambda-cyhalothrin in lizards (Eremias argus) following oral exposure. Environmental Pollution. 2018; 232: 300-309. doi: 10.1016/j.envpol.2017.09.072
7. Ibrahim HM. Evaluation of the Immunotoxic Effects of Sub-Chronic Doses of Lambda-Cyhalothrin in Murine Model. MOJ Immunology. 2016; 3(6). doi: 10.15406/moji.2016.03.00108
8. Gasmi S, Rouabhi R, Kebieche M, et al. Effects of Deltamethrin on striatum and hippocampus mitochondrial integrity and the protective role of Quercetin in rats. Environmental Science and Pollution Research. 2017; 24(19): 16440-16457. doi: 10.1007/s11356-017-9218-8
9. Allache F, Demnati F, Houhou MA. Population changes of Tuta absoluta (Gelechiidae) and fruit loss estimates on three tomato cultivars in greenhouses in Biskra, Algeria. Environmental and Experimental Biology. 2017. doi: 10.22364/eeb.15.20
10. Fetoui H, Garoui EM, Zeghal N. Lambda-cyhalothrin-induced biochemical and histopathological changes in the liver of rats: Ameliorative effect of ascorbic acid. Experimental and Toxicologic Pathology. 2009; 61(3): 189-196. doi: 10.1016/j.etp.2008.08.002
11. Aouey B, Fares E, Chtourou Y, et al. Lambda-cyhalothrin exposure alters purine nucleotide hydrolysis and nucleotidase gene expression pattern in platelets and liver of rats. Chemico-Biological Interactions. 2019; 311: 108796. doi: 10.1016/j.cbi.2019.108796
12. Ansari RW, Shukla RK, Yadav RS, et al. Cholinergic Dysfunctions and Enhanced Oxidative Stress in the Neurobehavioral Toxicity of Lambda-Cyhalothrin in Developing Rats. Neurotoxicity Research. 2012; 22(4): 292-309. doi: 10.1007/s12640-012-9313-z
13. Bush D, Bisby JA, Bird CM, et al. Human hippocampal theta power indicates movement onset and distance travelled. Proceedings of the National Academy of Sciences. 2017; 114(46): 12297-12302. doi: 10.1073/pnas.1708716114
14. Aouey B, Derbali M, Chtourou Y, et al. Pyrethroid insecticide lambda-cyhalothrin and its metabolites induce liver injury through the activation of oxidative stress and proinflammatory gene expression in rats following acute and subchronic exposure. Environmental Science and Pollution Research. 2017; 24(6): 5841-5856. doi: 10.1007/s11356-016-8323-4
15. Yahia D, Ali MF, Abd El-Maguid DS. Estimation of bone marrow DNA damage induced by lambda cyhalothrin and dimethoate insecticides using alkaline comet assay. J Adv Vet Res. 2019; 9: 23-28.
16. Dhikav V, Anand K. Hippocampus in health and disease: An overview. Annals of Indian Academy of Neurology. 2012; 15(4): 239. doi: 10.4103/0972-2327.104323
17. Hussein MMA, Ahmed MM. The Th1/Th2 paradigm in lambda cyhalothrin-induced spleen toxicity: The role of thymoquinone. Environmental Toxicology and Pharmacology. 2016; 41: 14-21. doi: 10.1016/j.etap.2015.11.008
18. Martins EN, Pessano NTC, Leal L, et al. Protective effect of Melissa officinalis aqueous extract against Mn-induced oxidative stress in chronically exposed mice. Brain Research Bulletin. 2012; 87(1): 74-79. doi: 10.1016/j.brainresbull.2011.10.003
19. Cole SL, Vassar R. The Alzheimer’s disease Beta-secretase enzyme, BACE1. Molecular Neurodegeneration. 2007; 2(1): 22. doi: 10.1186/1750-1326-2-22
20. Gomes NGM, Campos MG, Órfão JMC, et al. Plants with neurobiological activity as potential targets for drug discovery. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2009; 33(8): 1372-1389. doi: 10.1016/j.pnpbp.2009.07.033
21. Fernandes RPP, Trindade MA, Tonin FG, et al. Evaluation of antioxidant capacity of 13 plant extracts by three different methods: cluster analyses applied for selection of the natural extracts with higher antioxidant capacity to replace synthetic antioxidant in lamb burgers. Journal of Food Science and Technology. 2015; 53(1): 451-460. doi: 10.1007/s13197-015-1994-x
22. Milevskaya VV, Temerdashev ZA, Butyl’skaya TS, et al. Determination of phenolic compounds in medicinal plants from the Lamiaceae family. Journal of Analytical Chemistry. 2017; 72(3): 342-348. doi: 10.1134/s1061934817030091
23. Sedighi M, Faghihi M, Rafieian-kopaei M, et al. Cardioprotective effect of ethanolic leaf extract of Melissa officinalis L against regional ischemia-induced arrhythmia and heart injury after five days of reperfusion in rats. IJPR. 2019; 18(3). doi: 10.22037/ijpr.2019.1100761
24. Ozarowski M, Mikolajczak PL, Piasecka A, et al. Influence of the Melissa officinalis Leaf Extract on Long-Term Memory in Scopolamine Animal Model with Assessment of Mechanism of Action. Evidence-Based Complementary and Alternative Medicine. 2016; 2016: 1-17. doi: 10.1155/2016/9729818
25. Carvalho NC de, Corrêa-Angeloni MJF, Leffa DD, et al. Evaluation of the genotoxic and antigenotoxic potential of Melissa officinalis in mice. Genetics and Molecular Biology. 2011; 34(2): 290-297. doi: 10.1590/s1415-47572011000200021
26. Bruneton J. Pharmacognosy, Phytochemistry, Medicinal Plants. E. Lavoisier; 2015.
27. Chouit Z, Djellal D, Haddad S, et al. Potentiation of the apoptotic signaling pathway in both the striatum and hippocampus and neurobehavioral impairment in rats exposed chronically to a low−dose of cadmium. Environmental Science and Pollution Research. 2020; 28(3): 3307-3317. doi: 10.1007/s11356-020-10755-7
28. Li J, Yu W, Li XT, et al. The effects of propofol on mitochondrial dysfunction following focal cerebral ischemia-reperfusion in rats. Neuropharmacology. 2014; 77: 358-368. doi: 10.1016/j.neuropharm.2013.08.029
29. Ortiz-Jiménez DJ, López-Aquino CM, Flores-Herrera C, et al. A simple method for mitochondrial respiration and calcium uptake assessment in pollen tubes. Methods X. 2019; 6: 1741-1746. doi: 10.1016/j.mex.2019.07.023
30. Ahmed Z, Cooper J, Murray TK, et al. A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: the pattern of spread is determined by connectivity, not proximity. Acta Neuropathologica. 2014; 127(5): 667-683. doi: 10.1007/s00401-014-1254-6
31. Esterbauer H. Cytotoxicity and genotoxicity of lipid-oxidation products. The American Journal of Clinical Nutrition. 1993; 57(5): 779S-786S. doi: 10.1093/ajcn/57.5.779s
32. Reznick AZ, Packer L. Oxidative damage to proteins: Spectrophotometric method for carbonyl assay. Methods Enzymol. 1994; 233: 357-363. doi: 10.1016/S0076-6879(94)33041-7
33. Ou P, Wolff SP. A discontinuous method for catalase determination at “near physiological” concentrations of H2O2 and its application to the study of H2O2 fluxes within cells. Journal Biochemical Biophysics Methods. 1996; 31: 59-67. doi: 10.1016/0165-022X(95)00039-T
34. Ellman GL. Tissue sulfhydryl groups. Arch Biochemical Biophysics. 1959; 82: 70-77. doi: 10.1016/0003-9861(59)90090-6
35. Davis JS, Balinsky JB, Harington JS, Shepherd JB. Assay, purification, properties and mechanism of action of γ glutamylcysteine synthetase from the liver of the rat and Xenopus laevis. Biochemical Journal. 1973; 133(4): 667-678. doi.org/10.1042/bj1330667
36. Marklund S, Marklund G. Involvement of the Superoxide Anion Radical in the Autoxidation of Pyrogallol and a Convenient Assay for Superoxide Dismutase. European Journal of Biochemistry. 1974; 47(3): 469-474. doi: 10.1111/j.1432 1033.1974.tb03714.x
37. Aebi H. Catalase in Vitro. Methods Enzymol. 1984; 105: 121-126. doi:10.1016/S0076-6879(84)05016-3
38. Gonzler WA, Leopold F, Wolfgang AG. The term glutathione peroxidase (glutathione: H2O2 oxidoreductase, EC 1.11.1.9) is reserved for the selenoprotein catalyzing the reaction: Heal. San Fr. 1984; 105: 114-120.
39. Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacol. 1961; 7: 88-95. doi: 10.1016/0006-2952(61)90145-9
40. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochemical. 1976; 72: 248-254. doi: 10.1016/0003-2697(76)90527-3
41. Cardoso O, Puga S, Brandão F, et al. Oxidative stress profiles in brain point out a higher susceptibility of fish to waterborne divalent mercury compared to dietary organic mercury. Marine Pollution Bulletin. 2017; 122(1-2): 110-121. doi: 10.1016/j.marpolbul.2017.06.029
42. Valko M, Rhodes CJ, Moncol J, et al. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chemico-Biological Interactions. 2006; 160(1): 1-40. doi: 10.1016/j.cbi.2005.12.009
43. Samarghandian S, Azimi-Nezhad M, Farkhondeh T, et al. Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney. Biomedicine & Pharmacotherapy. 2017; 87: 223-229. doi: 10.1016/j.biopha.2016.12.105
44. White BC, Sullivan JM, DeGracia DJ, et al. Brain ischemia and reperfusion: Molecular mechanisms of neuronal injury. Journal of the neurological sciences. 2000; 179(1-2): 1-33. doi: 10.1016/S0022-510X(00)00386-5
45. Webster KA. Mitochondrial Membrane Permeabilization and Cell Death During Myocardial Infarction: Roles of Calcium and Reactive Oxygen Species. Future Cardiology. 2012; 8(6): 863-884. doi: 10.2217/fca.12.58
46. Sui Y, Stehno‐Bittel L, Li S, et al. CXCL10‐induced cell death in neurons: role of calcium dysregulation. European Journal of Neuroscience. 2006; 23(4): 957-964. doi: 10.1111/j.1460-9568.2006.04631.x
47. Stefanatos R, Sanz A. The role of mitochondrial ROS in the aging brain. FEBS Letters. 2017; 592(5): 743-758. doi: 10.1002/1873-3468.12902
48. Gargouri B, Bhatia HS, Bouchard M, et al. Inflammatory and oxidative mechanisms potentiate bifenthrin-induced neurological alterations and anxiety—like behavior in adult rats. Toxicology Letters. 2018; 294: 73-86. doi: 10.1016/j.toxlet.2018.05.020
49. Gargouri B, Bouchard M, Saliba SW, et al. Repeated bifenthrin exposure alters hippocampal Nurr-1/AChE and induces depression-like behavior in adult rats. Behavioral Brain Research. 2019; 370: 111898. doi: 10.1016/j.bbr.2019.04.012
50. Hamdy SM, Shaaban AM, El-khayaht ZA, et al. Therapeutic effect of Moringa oleifera pods extract and Raspberry ketone against Thioacetamide toxicity in male rats. Biochemistry Letters. 2019; 14(1): 49-63. doi: 10.21608/blj.2019.47563
51. Martínez MA, Ares I, Rodríguez JL, et al. Pyrethroid insecticide lambda-cyhalothrin induces hepatic cytochrome P450 enzymes, oxidative stress and apoptosis in rats. Science of The Total Environment. 2018; 631-632: 1371-1382. doi: 10.1016/j.scitotenv.2018.03.030
52. El-Demerdash FM. Lipid peroxidation, oxidative stress and acetylcholinesterase in rat brain exposed to organophosphate and pyrethroid insecticides. Food and Chemical Toxicology. 2011; 49(6): 1346-1352. doi: 10.1016/j.fct.2011.03.018
53. Hsu SS, Jan CR, Liang WZ. The investigation of the pyrethroid insecticide lambda-cyhalothrin (LCT)-affected Ca2+ homeostasis and -activated Ca2+-associated mitochondrial apoptotic pathway in normal human astrocytes: The evaluation of protective effects of BAPTA-AM (a selective Ca2+ chelator). NeuroToxicology. 2018; 69: 97-107. doi: 10.1016/j.neuro.2018.09.009
54. Bizzozero OA. Protein Carbonylation in Neurodegenerative and Demyelinating CNS Diseases. Handb Neurochem Mol Neurobiology. 2009; 543-562. doi: 10.1007/978-0-387-30375-8_23
55. Nyström T. Role of oxidative carbonylation in protein quality control and senescence. The EMBO Journal. 2005; 24(7): 1311-1317. doi: 10.1038/sj.emboj.7600599
56. Wang X, Martínez MA, Dai M, et al. Permethrin-induced oxidative stress and toxicity and metabolism. A review. Environmental Research. 2016; 149: 86-104. doi: 10.1016/j.envres.2016.05.003
57. Lu K, Cheng Y, Li W, et al. Activation of CncC pathway by ROS burst regulates cytochrome P450 CYP6AB12 responsible for λ-cyhalothrin tolerance in Spodoptera litura. Journal of Hazardous Materials. 2020; 387: 121698. doi: 10.1016/j.jhazmat.2019.121698
58. Benaicha B, Rouabhi R, Gasmi S et al. Triggering Mitochondrial Dysfunction and Apoptosis Under Chronic Low-dose Lambda-cyhalothrin Expo. Journal of Moldova. 2021. doi: 10.21203/rs.3.rs-801284/v1
59. Xu X, Duan S, Yi F, et al. Mitochondrial Regulation in Pluripotent Stem Cells. Cell Metabolism. 2013; 18(3): 325-332. doi: 10.1016/j.cmet.2013.06.005
60. Zhang Y, Chang Y, Cao H, et al. Potential threat of Chlorpyrifos to human liver cells via the caspase-dependent mitochondrial pathways. Food and Agricultural Immunology. 2017; 29(1): 294-305. doi: 10.1080/09540105.2017.1373271
61. Song C, Charli A, Luo J, et al. Mechanistic Interplay Between Autophagy and Apoptotic Signaling in Endosulfan-Induced Dopaminergic Neurotoxicity: Relevance to the Adverse Outcome Pathway in Pesticide Neurotoxicity. Toxicological Sciences. 2019; 169(2): 333-352. doi: 10.1093/toxsci/kfz049
62. Liu X, Song X, Luan D, et al. Real-Time in Situ Visualizing of the Sequential Activation of Caspase Cascade Using a Multicolor Gold-Selenium Bonding Fluorescent Nanoprobe. Analytical Chemistry. 2019; 91(9): 5994-6002. doi: 10.1021/acs.analchem.9b00452
63. Chtourou Y, Aouey B, Aroui S, et al. Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat. Chemistry Biology Interactions. 2016; 243: 1-9. doi: 10.1016/j.cbi.2015.11.019
64. Gasmi S, Benaicha B, Kebieche M, Mennai I. Preventive effects of citrullus colocynthis. L plant extract on deltamethrin pesticide induced pneumotoxicity in wister rats. Journal of Microbiology, Biotechnology and Food Sciences. 2022. 11(6). doi: 10.55251/jmbfs.5268
65. Bayat M, Azami Tameh A, Hossein Ghahremani M, et al. Neuroprotective properties of Melissa officinalis after hypoxic-ischemic injury both in vitro and in vivo. DARU Journal of Pharmaceutical Sciences. 2012; 20(1). doi: 10.1186/2008-2231-20-42
66. Weitzel C, Petersen M. Cloning and characterisation of rosmarinic acid synthase from Melissa officinalis L. Phytochemistry. 2011; 72(7): 572-578. doi: 10.1016/j.phytochem.2011.01.039
67. Shakeri A, Sahebkar A, Javadi B. Melissa officinalis L—A review of its traditional uses, phytochemistry and pharmacology. Journal of Ethnopharmacology. 2016; 188: 204-228. doi: 10.1016/j.jep.2016.05.010
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