Glyphosate-based herbicide impairs energy metabolism and increases autophagy in C6 astroglioma cell line

References

• Aebi, H. 1984. Catalase in vitro. Meth. Enzymol 105:121–26.
   PubMed Web of Science ®Google Scholar
• Aksenov, M., M. Aksenova, D. A. Butterfield, and W. R. Markesbery. 2000. Oxidative modification of creatine kinase BB in Alzheimer’s disease brain. J. Neurochem. 74:2520–27.
   PubMed Web of Science ®Google Scholar
• Annett, R., H. R. Habibi, and A. Hontela. 2014. Impact of glyphosate and glyphosate-based herbicides on the freshwater environment. J Appl Toxicol 34:458–79. doi:10.1002/jat.v34.5.
   PubMed Web of Science ®Google Scholar
• Astiz, M., M. J. de Alaniz, and C. A. Marra. 2009. Effect of pesticides on cell survival in liver and brain rat tissues. Ecotoxicol. Environ. Saf. 72:2025–32. doi:10.1016/j.ecoenv.2009.05.001.
   PubMed Web of Science ®Google Scholar
• Astiz, M., M. J. de Alaniz, and C. A. Marra. 2012. The oxidative damage and inflammation caused by pesticides are reverted by lipoic acid in rat brain. Neurochem. Int. 61:1231–41. doi:10.1016/j.neuint.2012.09.003.
   PubMed Web of Science ®Google Scholar
• Bai, S. H., and S. M. Ogbourne. 2016. Glyphosate: Environmental contamination, toxicity and potential risks to human health via food contamination. Environ Sci Pollut Res Int 23:18988–9001. doi:10.1007/s11356-016-7425-3.
   PubMed Web of Science ®Google Scholar
• Bailey, D. C., C. E. Todt, S. L. Burchfield, A. S. Pressley, R. D. Denney, I. B. Snapp, R. Negga, W. L. Traynor, and V. A. Fitsanakis. 2018. Chronic exposure to a glyphosate-containing pesticide leads to mitochondrial dysfunction and increased reactive oxygen species production. Caenorhabditis Elegans. Environ. Toxicol. Pharmacol. 57:46–52. doi:10.1016/j.etap.2017.11.005.
   PubMed Web of Science ®Google Scholar
• Bali, Y. A., N. E. Kaikai, S. Ba-M’hamed, and M. Bennis. 2019. Learning and memory impairments associated to acetylcholinesterase inhibition and oxidative stress following glyphosate based-herbicide exposure in mice. Toxicol. 415:18–25. doi:10.1016/j.tox.2019.01.010.
   PubMed Web of Science ®Google Scholar
• Baltazar, M. T., R. J. Dinis-Oliveira, M. de Lourdes Bastos, A. M. Tsatsakis, J. A. Duarte, and F. Carvalho. 2014. Pesticides exposure as etiological factors of Parkinson’s disease and other neurodegenerative diseases–a mechanistic approach. Toxicol. Lett. 230:85–103. doi:10.1016/j.toxlet.2014.01.039.
   PubMed Web of Science ®Google Scholar
• Benachour, N., and G. E. Seralini. 2009. Glyphosate formulations induce apoptosis and necrosis in human umbilical, embryonic, and placental cells. Chem. Res. Toxicol. 22:97–105. doi:10.1021/tx800218n.
   PubMed Web of Science ®Google Scholar
• Bindokas, V. P., J. Jordan, C. C. Lee, and R. J. Miller. 1996. Superoxide production in rat hippocampal neurons: Selective imaging with hydroethidine. J. Neurosci. 16:1324–36. doi:10.1523/JNEUROSCI.16-04-01324.1996.
   PubMed Web of Science ®Google Scholar
• Braz-Mota, S., H. Sadauskas-Henrique, R. M. Duarte, A. L. Val, and V. M. Almeida-Val. 2015. Roundup(R) exposure promotes gills and liver impairments, DNA damage and inhibition of brain cholinergic activity in the Amazon teleost fish. Colossoma Macropomum. Chemosphere 135:53–60. doi:10.1016/j.chemosphere.2015.03.042.
   PubMed Web of Science ®Google Scholar
• Cassina, A., and R. Radi. 1996. Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch. Biochem. Biophys. 328:309–16. doi:10.1006/abbi.1996.0178.
   PubMed Web of Science ®Google Scholar
• Cattani, D., P. A. Cesconetto, M. K. Tavares, E. B. Parisotto, P. A. De Oliveira, C. E. H. Rieg, M. C. Leite, R. D. S. Prediger, N. C. Wendt, G. Razzera, et al. 2017. Developmental exposure to glyphosate-based herbicide and depressive-like behavior in adult offspring: Implication of glutamate excitotoxicity and oxidative stress. Toxicol. 387:67–80. doi:10.1016/j.tox.2017.06.001.
   PubMed Web of Science ®Google Scholar
• Cattani, D., V. L. de Liz Oliveira, C. E. Cavalli, J. T. Heinz Rieg, T. Domingues, C. I. Dal-Cim, F. R. Tasca, M. B. Silva, and A. Zamoner. 2014. Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity. Toxicol. 320:34–45. doi:10.1016/j.tox.2014.03.001.
   PubMed Web of Science ®Google Scholar
• Chaufan, G., I. Coalova, and C. R. de Molina Mdel. 2014. Glyphosate commercial formulation causes cytotoxicity, oxidative effects, and apoptosis on human cells: Differences with its active ingredient. Int. J. Toxicol. 33:29–38. doi:10.1177/1091581813517906.
   PubMed Web of Science ®Google Scholar
• Chorfa, A., D. Betemps, E. Morignat, C. Lazizzera, K. Hogeveen, T. Andrieu, and T. Baron. 2013. Specific pesticide-dependent increases in alpha-synuclein levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines. Toxicol. Sci. 133:289–97. doi:10.1093/toxsci/kft076.
   PubMed Web of Science ®Google Scholar
• Coalova, I., C. R. de Molina Mdel, and G. Chaufan. 2014. Influence of the spray adjuvant on the toxicity effects of a glyphosate formulation. Toxicol In Vitro 28:1306–11. doi:10.1016/j.tiv.2014.06.014.
   PubMed Web of Science ®Google Scholar
• Cooper, A. J., and B. S. Kristal. 1997. Multiple roles of glutathione in the central nervous system. Biol. Chem. 378:793–802.
   PubMed Web of Science ®Google Scholar
• Cotto, B., K. Natarajaseenivasan, and D. Langford. 2019. Astrocyte activation and altered metabolism in normal aging, age-related CNS diseases, and HAND. J. Neurovirol. 25:722–33. doi:10.1007/s13365-019-00721-6.
   PubMed Web of Science ®Google Scholar
• Culbreth, M. E., J. A. Harrill, T. M. Freudenrich, W. R. Mundy, and T. J. Shafer. 2012. Comparison of chemical-induced changes in proliferation and apoptosis in human and mouse neuroprogenitor cells. Neurotoxicol. 33:1499–510. doi:10.1016/j.neuro.2012.05.012.
   PubMed Web of Science ®Google Scholar
• de Almeida, L. M., M. C. Leite, A. P. Thomazi, C. Battu, P. Nardin, L. S. Tortorelli, C. Zanotto, T. Posser, S. T. Wofchuk, R. B. Leal, et al. 2008. Resveratrol protects against oxidative injury induced by H2O2 in acute hippocampal slice preparations from Wistar rats. Arch. Biochem. Biophys. 480:27–32. doi:10.1016/j.abb.2008.09.006.
   PubMed Web of Science ®Google Scholar
• de Sosa, L., S. Gutierrez, J. P. Petiti, C. M. Palmeri, I. D. Mascanfroni, M. Soaje, A. L. De Paul, and A. I. Torres. 2012. 17-beta-Estradiol modulates the prolactin secretion induced by TRH through membrane estrogen receptors via PI3K/Akt in female rat anterior pituitary cell culture. Am. J. Physiol. Endocrinol. Metab. 302:E1189–E1197. doi:10.1152/ajpendo.00408.2011.
   PubMed Web of Science ®Google Scholar
• Defarge, N., E. Takacs, V. L. Lozano, J. Mesnage, S. de Vendomois, G. E. Seralini, and A. Szekacs. 2016. Co-formulants in glyphosate-based herbicides disrupt aromatase activity in human cells below toxic levels. Int J Environ Res Public Health 13:pii: E264. doi:10.3390/ijerph13030264.
   PubMed Web of Science ®Google Scholar
• Dinkova-Kostova, A. T., W. D. Holtzclaw, R. N. Cole, K. Itoh, N. Wakabayashi, Y. Katoh, M. Yamamoto, and P. Talalay. 2002. Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc. Natl. Acad. Sci. U.S.A. 99:11908–13. doi:10.1073/pnas.172398899.
   PubMed Web of Science ®Google Scholar
• Dos Santos, A. Q., P. Nardin, C. Funchal, L. M. de Almeida, M. C. Jacques-Silva, S. T. Wofchuk, C. A. Goncalves, and C. Gottfried. 2006. Resveratrol increases glutamate uptake and glutamine synthetase activity in C6 glioma cells. Arch. Biochem. Biophys. 453:161–67. doi:10.1016/j.abb.2006.06.025.
   PubMed Web of Science ®Google Scholar
• Drake, K. R., M. Kang, and A. K. Kenworthy. 2010. Nucleocytoplasmic distribution and dynamics of the autophagosome marker EGFP-LC3. PLoS ONE 5:e9806. doi:10.1371/journal.pone.0009806.
   PubMed Web of Science ®Google Scholar
• Duke, S. O., and S. B. Powles. 2008. Glyphosate: A once-in-a-century herbicide. Pest Manage Sci. 64:319–25. doi:10.1002/ps.1518.
   PubMed Web of Science ®Google Scholar
• Ellman, G. L. 1959. Tissue sulfhydryl groups. Arch. Biochem. Biophys. 82:70–77. doi:10.1016/0003-9861(59)90090-6.
   PubMed Web of Science ®Google Scholar
• Erecinska, M., D. Nelson, M. Yudkoff, and I. A. Silver. 1994. Energetics of the nerve terminal in relation to central nervous system function. Biochem. Soc. Trans. 22:959–65. doi:10.1042/bst0220959.
   PubMed Web of Science ®Google Scholar
• Fischer, J. C., W. Ruitenbeek, J. A. Berden, J. M. Trijbels, J. H. Veerkamp, A. M. Stadhouders, R. C. Sengers, and A. J. Janssen. 1985. Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin. Chim. Acta 153:23–36. doi:10.1016/0009-8981(85)90135-4.
   PubMed Web of Science ®Google Scholar
• Fiskum, G., A. N. Murphy, and M. F. Beal. 1999. Mitochondria in neurodegeneration: Acute ischemia and chronic neurodegenerative diseases. J. Cereb. Blood Flow Metab. 19:351–69. doi:10.1097/00004647-199904000-00001.
   PubMed Web of Science ®Google Scholar
• Freire, C., and S. Koifman. 2012. Pesticide exposure and Parkinson’s disease: Epidemiological evidence of association. Neurotoxicol. 33:947–71. doi:10.1016/j.neuro.2012.05.011.
   PubMed Web of Science ®Google Scholar
• Fu, H., S. Qiu, X. Yao, F. Gao, P. Tan, T. Teng, and B. Shi. 2019. Toxicity of glyphosate in feed for weanling piglets and the mechanism of glyphosate detoxification by the liver nuclear receptor CAR/PXR pathway. J. Hazard. Mater. 387:121707. doi:10.1016/j.jhazmat.2019.121707.
   PubMed Web of Science ®Google Scholar
• Gallegos, C. E., C. J. Baier, M. Bartos, C. Bras, S. Dominguez, N. Monaco, F. Gumilar, M. S. Gimenez, and A. Minetti. 2018. Perinatal glyphosate-based herbicide exposure in rats alters brain antioxidant status, glutamate and acetylcholine metabolism and affects recognition memory. Neurotoxicol. Res. 34:363–74. doi:10.1007/s12640-018-9894-2.
   PubMed Web of Science ®Google Scholar
• Gasnier, C., C. Dumont, N. Benachour, E. Clair, M. C. Chagnon, and G. E. Seralini. 2009. Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines. Toxicol. 262:184–1891. doi:10.1016/j.tox.2009.06.006.
   PubMed Web of Science ®Google Scholar
• Gazzaniga, P., A. Gradilone, R. Vercillo, O. Gandini, I. Silvestri, M. Napolitano, L. Albonici, A. Vincenzoni, M. Gallucci, L. Frati, et al. 1996. Bcl-2/bax mRNA expression ratio as prognostic factor in low-grade urinary bladder cancer. Int. J. Cancer 69:100–04. doi:10.1002/(SICI)1097-0215(19960422)69:2<100::AID-IJC5>3.0.CO;2-4.
   PubMed Web of Science ®Google Scholar
• Gomes, M. P., and P. Juneau. 2016. Oxidative stress in duckweed (Lemna minor L.) induced by glyphosate: Is the mitochondrial electron transport chain a target of this herbicide? Environ. Pollut. 218:402–09. doi:10.1016/j.envpol.2016.07.019.
   PubMed Web of Science ®Google Scholar
• Gui, Y. X., X. N. Fan, H. M. Wang, G. Wang, and S. D. Chen. 2012. Glyphosate induced cell death through apoptotic and autophagic mechanisms. Neurotoxicol Teratol 34:344–49. doi:10.1016/j.ntt.2012.03.005.
   PubMed Web of Science ®Google Scholar
• Guilherme, S., I. Gaivao, M. A. Santos, and M. Pacheco. 2010. European eel (Anguilla anguilla) genotoxic and pro-oxidant responses following short-term exposure to Roundup–a glyphosate-based herbicide. Mutagenesis 25:523–30. doi:10.1093/mutage/geq038.
   PubMed Web of Science ®Google Scholar
• Hao, Y., W. Xu, J. Gao, Y. Zhang, Y. Yang, and L. Tao. 2019. Roundup-induced AMPK/mTOR-mediated autophagy in human A549 cells. J. Agric. Food Chem. 67:11364–72. doi:10.1021/acs.jafc.9b04679.
   PubMed Web of Science ®Google Scholar
• Hemmer, W., E. Zanolla, E. M. Furter-Graves, H. M. Eppenberger, and T. Wallimann. 1994. Creatine kinase isoenzymes in chicken cerebellum: Specific localization of brain-type creatine kinase in Bergmann glial cells and muscle-type creatine kinase in Purkinje neurons. Eur. J. Neurosci. 6:538–49. doi:10.1111/j.1460-9568.1994.tb00298.x.
   PubMed Web of Science ®Google Scholar
• Hippert, M. M., P. S. O’Toole, and A. Thorburn. 2006. Autophagy in cancer: Good, bad, or both? Cancer Res. 66:9349–51. doi:10.1158/0008-5472.CAN-06-1597.
   PubMed Web of Science ®Google Scholar
• Hofmann, J. N., L. E. Beane Freeman, C. F. Lynch, G. Andreotti, K. W. Thomas, D. P. Sandler, S. A. Savage, and M. C. Alavanja. 2015. The biomarkers of exposure and effect in agriculture (BEEA) study: Rationale, design, methods, and participant characteristics. J. Toxicol. Environ. Health Part A 78:1338–47. doi:10.1080/15287394.2015.1091414.
   PubMed Web of Science ®Google Scholar
• Hughes, B. P. 1962. A method for the estimation of serum creatine kinase and its use in comparing creatine kinase and aldolase activity in normal and pathological sera. Clin. Chim. Acta 7:597–603. doi:10.1016/0009-8981(62)90137-7.
   PubMed Web of Science ®Google Scholar
• Islam, M. T. 2017. Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol. Res. 39:73–82. doi:10.1080/01616412.2016.1251711.
   PubMed Web of Science ®Google Scholar
• Itoh, K., T. Chiba, S. Takahashi, T. Ishii, K. Igarashi, Y. Katoh, T. Oyake, N. Hayashi, K. Satoh, I. Hatayama, et al. 1997. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun. 236:313–22. doi:10.1006/bbrc.1997.6943.
   PubMed Web of Science ®Google Scholar
• Kenyon, G. L. 1996. Energy metabolism. Creatine kinase shapes up. Nature 381:281–82. doi:10.1038/381281a0.
   PubMed Web of Science ®Google Scholar
• Kobayashi, A., M. I. Kang, Y. Watai, K. I. Tong, T. Shibata, K. Uchida, and M. Yamamoto. 2006. Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1. Mol. Cell. Biol. 26:221–29. doi:10.1128/MCB.26.1.221-229.2006.
   PubMed Web of Science ®Google Scholar
• Koller, V. J., M. Furhacker, A. Nersesyan, M. Misik, M. Eisenbauer, and S. Knasmueller. 2012. Cytotoxic and DNA-damaging properties of glyphosate and Roundup in human-derived buccal epithelial cells. Arch. Toxicol. 86:805–13. doi:10.1007/s00204-012-0804-8.
   PubMed Web of Science ®Google Scholar
• Konorev, E. A., N. Hogg, and B. Kalyanaraman. 1998. Rapid and irreversible inhibition of creatine kinase by peroxynitrite. FEBS Lett. 427:171–74. doi:10.1016/S0014-5793(98)00413-X.
   PubMed Web of Science ®Google Scholar
• Kubli, D. A., M. Q. Cortez, A. G. Moyzis, R. H. Najor, Y. Lee, and A. B. Gustafsson. 2015. PINK1 is dispensable for mitochondrial recruitment of Parkin and activation of mitophagy in cardiac myocytes. PLoS ONE 10:e0130707. doi:10.1371/journal.pone.0130707.
   PubMed Web of Science ®Google Scholar
• Kwiatkowska, M., E. Reszka, K. Wozniak, E. Jablonska, J. Michalowicz, and B. Bukowska. 2017. DNA damage and methylation induced by glyphosate in human peripheral blood mononuclear cells (in vitro study). Food Chem. Toxicol. 105:93–98. doi:10.1016/j.fct.2017.03.051.
   PubMed Web of Science ®Google Scholar
• Larsen, K., R. Najle, A. Lifschitz, and G. Virkel. 2012. Effects of sub-lethal exposure of rats to the herbicide glyphosate in drinking water: Glutathione transferase enzyme activities, levels of reduced glutathione and lipid peroxidation in liver, kidneys and small intestine. Environ. Toxicol. Pharmacol. 34:811–18. doi:10.1016/j.etap.2012.09.005.
   PubMed Web of Science ®Google Scholar
• Larsen, K., R. Najle, A. Lifschitz, M. L. Mate, C. Lanusse, and G. L. Virkel. 2014. Effects of sublethal exposure to a glyphosate-based herbicide formulation on metabolic activities of different xenobiotic-metabolizing enzymes in rats. Int. J. Toxicol. 33:307–18. doi:10.1177/1091581814540481.
   PubMed Web of Science ®Google Scholar
• Lin, M. T., and M. F. Beal. 2006. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–95. doi:10.1038/nature05292.
   PubMed Web of Science ®Google Scholar
• Liu, H., C. Dai, Y. Fan, B. Guo, K. Ren, T. Sun, and W. Wang. 2017. From autophagy to mitophagy: The roles of P62 in neurodegenerative diseases. J. Bioenerg. Biomembr. 49:413–22. doi:10.1007/s10863-017-9727-7.
   PubMed Web of Science ®Google Scholar
• Lowry, O. H., N. J. Rosebrough, A. L. Farr, and R. J. Randall. 1951. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193:265–75.
   PubMed Web of Science ®Google Scholar
• Ma, Q. 2013. Role of Nrf2 in oxidative stress and toxicity. Annu. Rev. Pharmacol. Toxicol. 53:401–26. doi:10.1146/annurev-pharmtox-011112-140320.
   PubMed Web of Science ®Google Scholar
• Martindale, J. L., and N. J. Holbrook. 2002. Cellular response to oxidative stress: Signaling for suicide and survival. J. Cell. Physiol. 192:1–15. doi:10.1002/(ISSN)1097-4652.
   PubMed Web of Science ®Google Scholar
• Martinez, M. A., J. L. Rodriguez, B. Lopez-Torres, M. Martinez, M. R. Martinez-Larranaga, J. E. Maximiliano, A. Anadon, and I. Ares. 2020. Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways. Environ Int 135:105414. doi:10.1016/j.envint.2019.105414.
   PubMed Web of Science ®Google Scholar
• Martini, C. N., M. Gabrielli, J. N. Brandani, and C. Vila Mdel. 2016. Glyphosate inhibits PPAR amma induction and differentiation of preadipocytes and is able to induce oxidative tress. J. Biochem. Mol. Toxicol. 30:404–13. doi:10.1002/jbt.21804.
   PubMed Web of Science ®Google Scholar
• Medhora, M., Y. Chen, S. Gruenloh, D. Harland, S. Bodiga, J. Zielonka, D. Gebremedhin, Y. Gao, J. R. Falck, S. Anjaiah, et al. 2008. 20-HETE increases superoxide production and activates NAPDH oxidase in pulmonary artery endothelial cells. Am. J. Physiol. Lung Cell Mol. Physiol. 294:L902–L911. doi:10.1152/ajplung.00278.2007.
   PubMed Web of Science ®Google Scholar
• Menendez-Helman, R. J., G. V. Ferreyroa, M. D. S. Afonso, and A. Salibian. 2012. Glyphosate as an acetylcholinesterase inhibitor. Cnesterodon Decemmaculatus. Bull Environ Contam Toxicol 88:6–9. doi:10.1007/s00128-011-0423-8.
   PubMed Web of Science ®Google Scholar
• Mesnage, R., B. Bernay, and G. E. Seralini. 2013. Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity. Toxicol. 313:122–28. doi:10.1016/j.tox.2012.09.006.
   PubMed Web of Science ®Google Scholar
• Mladinic, M., P. Perkovic, and D. Zeljezic. 2009. Characterization of chromatin instabilities induced by glyphosate, terbuthylazine and carbofuran using cytome FISH assay. Toxicol. Lett. 189:130–37. doi:10.1016/j.toxlet.2009.05.012.
   PubMed Web of Science ®Google Scholar
• Modesto, K. A., and C. B. Martinez. 2010a. Effects of roundup transorb on fish: Hematology, antioxidant defenses and acetylcholinesterase activity. Chemosphere 81:781–87. doi:10.1016/j.chemosphere.2010.07.005.
   PubMed Web of Science ®Google Scholar
• Modesto, K. A., and C. B. Martinez. 2010b. Roundup causes oxidative stress in liver and inhibits acetylcholinesterase in muscle and brain of the fish. Prochilodus Lineatus. Chemosphere 78:294–99. doi:10.1016/j.chemosphere.2009.10.047.
   PubMed Web of Science ®Google Scholar
• Morais, V. A., and B. De Strooper. 2010. Mitochondria dysfunction and neurodegenerative disorders: Cause or consequence. J. Alzheimers Dis. 20 (Suppl 2):S255–S263. doi:10.3233/JAD-2010-100345.
   PubMedGoogle Scholar
• Moretto, A., and C. Colosio. 2011. Biochemical and toxicological evidence of neurological effects of pesticides: The example of Parkinson’s disease. Neurotoxicol. 32:383–91. doi:10.1016/j.neuro.2011.03.004.
   PubMed Web of Science ®Google Scholar
• Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Meth. 65:55–63. doi:10.1016/0022-1759(83)90303-4.
   PubMed Web of Science ®Google Scholar
• Mostafalou, S., and M. Abdollahi. 2013. Pesticides and human chronic diseases: evidences, mechanisms, and perspectives. Toxicol. Appl. Pharmacol. 268:157–77. doi:10.1016/j.taap.2013.01.025.
   PubMed Web of Science ®Google Scholar
• Nel, A., T. Xia, L. Madler, and N. Li. 2006. Toxic potential of materials at the nanolevel. Science 311:622–27. doi:10.1126/science.1114397.
   PubMed Web of Science ®Google Scholar
• Park, J. H., J. E. Lee, I. C. Shin, and H. C. Koh. 2013. Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells. Toxicol. Appl. Pharmacol. 268:55–67. doi:10.1016/j.taap.2013.01.013.
   PubMed Web of Science ®Google Scholar
• Peixoto, F. 2005. Comparative effects of the Roundup and glyphosate on mitochondrial oxidative phosphorylation. Chemosphere 61:1115–22. doi:10.1016/j.chemosphere.2005.03.044.
   PubMed Web of Science ®Google Scholar
• Pereira, A. G., M. L. Jaramillo, A. P. Remor, A. Latini, C. E. Davico, M. L. da Silva, Y. M. R. Muller, D. Ammar, and E. M. Nazari. 2018. Low-concentration exposure to glyphosate-based herbicide modulates the complexes of the mitochondrial respiratory chain and induces mitochondrial hyperpolarization in the Danio rerio brain. Chemosphere 209:353–62. doi:10.1016/j.chemosphere.2018.06.075.
   PubMed Web of Science ®Google Scholar
• Pieniążek, D., B. Bukowska, and W. Duda. 2004. Comparison of the effect of roundup ultra 360 SL pesticide and its active compound glyphosate on human erythrocytes. Pest Biochem Physiol. 79:6. doi:10.1016/j.pestbp.2004.03.003.
   Web of Science ®Google Scholar
• Qin, Y., X. Li, Y. Xiang, D. Wu, L. Bai, Z. Li, and Y. Liang. 2017. Toxic effects of glyphosate on diploid and triploid fin cell lines from misgurnus anguillicaudatus. Chemosphere 180:356–64. doi:10.1016/j.chemosphere.2017.03.098.
   PubMed Web of Science ®Google Scholar
• Samsel, A., and S. Seneff. 2015. Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies. Surg Neurol Int. 6:45. doi:10.4103/2152-7806.153876.
   PubMedGoogle Scholar
• Solomon, K. R., E. J. Marshall, and G. Carrasquilla. 2009. Human health and environmental risks from the use of glyphosate formulations to control the production of coca in Colombia: Overview and conclusions. J. Toxicol. Environ. Health Part A 72:914–20. doi:10.1080/15287390902929659.
   PubMed Web of Science ®Google Scholar
• Steinrucken, H. C., and N. Amrhein. 1980. The herbicide glyphosate is a potent inhibitor of 5-enolpyruvyl-shikimic acid-3-phosphate synthase. Biochem. Biophys. Res. Commun. 94:1207–12. doi:10.1016/0006-291X(80)90547-1.
   PubMed Web of Science ®Google Scholar
• Taguchi, K., H. Motohashi, and M. Yamamoto. 2011. Molecular mechanisms of the keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells 16:123–40.
   PubMed Web of Science ®Google Scholar
• Tizhe, E. V., N. D. Ibrahim, M. Y. Fatihu, I. I. Onyebuchi, B. D. George, S. F. Ambali, and J. M. Shallangwa. 2014. Influence of zinc supplementation on histopathological changes in the stomach, liver, kidney, brain, pancreas and spleen during subchronic exposure of wistar rats to glyphosate. Comp. Clin. Pathol. 23:1535–43.
   PubMedGoogle Scholar
• Tomimoto, H., K. Yamamoto, H. A. Homburger, and T. Yanagihara. 1993. Immunoelectron microscopic investigation of creatine kinase BB-isoenzyme after cerebral ischemia in gerbils. Acta Neuropathol. 86:447–55.
   PubMed Web of Science ®Google Scholar
• Tsui, M. T., and L. M. Chu. 2003. Aquatic toxicity of glyphosate-based formulations: Comparison between different organisms and the effects of environmental factors. Chemosphere 52:1189–97.
   PubMed Web of Science ®Google Scholar
• Twig, G., A. Elorza, A. J. Molina, H. Mohamed, J. D. Wikstrom, G. Walzer, L. Stiles, S. E. Haigh, S. Katz, G. Las, et al. 2008. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. Embo J. 27:433–46.
   PubMed Web of Science ®Google Scholar
• Uren Webster, T. M., and E. M. Santos. 2015. Global transcriptomic profiling demonstrates induction of oxidative stress and of compensatory cellular stress responses in brown trout exposed to glyphosate and roundup. BMC Genomics 16:32.
   PubMed Web of Science ®Google Scholar
• Vaccari, C., R. El Dib, H. Gomaa, L. C. Lopes, and J. L. de Camargo. 2019. Paraquat and Parkinson’s disease: A systematic review and meta-analysis of observational studies. J Toxixol Environ. Health B 22:172–202.
   PubMed Web of Science ®Google Scholar
• Voorhees, J. R., D. S. Rohlman, P. J. Lein, and A. A. Pieper. 2016. Neurotoxicity in preclinical models of occupational exposure to organophosphorus compounds. Front. Neurosci. 10:590.
   PubMed Web of Science ®Google Scholar
• Wallimann, T., and W. Hemmer. 1994. Creatine kinase in non-muscle tissues and cells. Mol. Cell. Biochem. 133-134:193–220.
   PubMed Web of Science ®Google Scholar
• Wang, P. F., M. J. McLeish, M. M. Kneen, G. Lee, and G. L. Kenyon. 2001. An unusually low pK(a) for Cys282 in the active site of human muscle creatine kinase. Biochem. 40:11698–705.
   PubMed Web of Science ®Google Scholar
• Zouaoui, K., S. Dulaurent, J. M. Gaulier, C. Moesch, and G. Lachatre. 2013. Determination of glyphosate and AMPA in blood and urine from humans: About 13 cases of acute intoxication. Forensic Sci. Int. 226:e20–e25.
   PubMed Web of Science ®Google Scholar