https://doi.org/10.4081/ejh.2021.3285
Antioxidant support to ameliorate the oxaliplatin-dependent microglial alteration: morphological and molecular study
Submitted: 1 June 2021
Accepted: 20 October 2021
Published: 10 November 2021
Accepted: 20 October 2021
Abstract Views: 853
PDF: 523
HTML: 6
HTML: 6
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Oxaliplatin is a third-generation chemotherapy drug mainly used for colorectal cancer treatment. However, it is also known to trigger neuropathy whose underlying neurobiological mechanisms are still under investigation and currently available treatments show limited efficacy. It is now established that neurons are not the only cell type involved in chronic pain and that glial cells, mainly astrocytes and microglia, are involved in the initiation and maintenance of neuropathy. Among all the pathogenetic factors involved in neuropathic pain, an oxaliplatin-dependent oxidative stress plays a predominant role. In our study, the antioxidant properties of magnesium (Mg), manganese (Mn) and zinc (Zn) salts were evaluated in order to counteract microglial activation induced by oxaliplatin. The antioxidant efficacy of these metals was evaluated by the means of molecular and morphological assays on the BV-2 microglial cell line. Our data clearly show that Mg, Mn and Zn are able to prevent oxaliplatin-dependent microglial alterations by reducing both oxidative and endoplasmic reticulum stress.
Kanavos P. The rising burden of cancer in the developing world. Ann Oncol 2006;17:viii15-23.
DOI: https://doi.org/10.1093/annonc/mdl983
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
DOI: https://doi.org/10.3322/caac.21492
Alcindor T, Beauger N. Oxaliplatin: a review in the era of molecularly targeted therapy. Curr Oncol 2011;18:18-25.
DOI: https://doi.org/10.3747/co.v18i1.708
Fischer J, Ganellin CR. Analogue‐based drug discovery. Weinheim, Wiley-VCH; 2006.
DOI: https://doi.org/10.1002/3527608001
Di Cesare Mannelli L, Pacini A, Micheli L, Tani A, Zanardelli M, Ghelardini C. Glial role in oxaliplatin-induced neuropathic pain. Exp Neurol 2014;261:22-33.
DOI: https://doi.org/10.1016/j.expneurol.2014.06.016
Di Cesare Mannelli L, Pacini A, Bonaccini L, Zanardelli M, Mello T, Ghelardini C. Morphologic Features and glial activation in rat oxaliplatin-dependent neuropathic pain. J Pain 2013;14:1585-600.
DOI: https://doi.org/10.1016/j.jpain.2013.08.002
Branca JJV, Maresca M, Morucci G, Becatti M, Paternostro F, Gulisano M, et al. Oxaliplatin-induced blood brain barrier loosening: a new point of view on chemotherapy-induced neurotoxicity. Oncotarget 2018;9:23426-38.
DOI: https://doi.org/10.18632/oncotarget.25193
Stankovic JSK, Selakovic D, Mihailovic V, Rosic G. Antioxidant supplementation in the treatment of neurotoxicity induced by platinum-based chemotherapeutics - A review. Int J Mol Sci 2020;26:7753.
DOI: https://doi.org/10.3390/ijms21207753
Pickering G, Morel V, Simen E, Cardot J-M, Moustafa F, Delage N, et al. Oral magnesium treatment in patients with neuropathic pain: a randomized clinical trial. Magnes Res 2011;24:28-35.
DOI: https://doi.org/10.1684/mrh.2011.0282
Visovsky C. Calcium and magnesium for oxaliplatin-induced neurotoxicity: Issues in study design, measurement, and analysis. J Adv Pract Oncol 2015;6:272-6.
DOI: https://doi.org/10.6004/jadpro.2015.6.3.9
Bocchi L, Branca JJV, Pacini S, Cosentino A, Morucci G, Ruggiero M. Effect of ultrasounds on neurons and microglia: Cell viability and automatic analysis of cell morphology. Biomed Signal Proc 2015;22:44-53.
DOI: https://doi.org/10.1016/j.bspc.2015.06.011
Branca JJV, Morucci G, Becatti M, Carrino D, Ghelardini C, Gulisano M, et al. Cannabidiol protects dopaminergic neuronal cells from cadmium. Int J Environ Res Public Health 2019;16:4420.
DOI: https://doi.org/10.3390/ijerph16224420
Carrino D, Branca JJV, Becatti M, Paternostro F, Morucci G, Gulisano M, et al. Alcohol-induced blood-brain barrier impairment: An in vitro study. Int J Environ Res Public Health 2021;18:2683.
DOI: https://doi.org/10.3390/ijerph18052683
Di Cesare Mannelli L, Zanardelli M, Failli P, Ghelardini C. Oxaliplatin-induced oxidative stress in nervous system-derived cellular models: Could it correlate with in vivo neuropathy? Free Radic Biol Med 2013;61:143-50.
DOI: https://doi.org/10.1016/j.freeradbiomed.2013.03.019
Fumagalli G, Monza L, Cavaletti G, Rigolio R, Meregalli C. Neuroinflammatory process involved in different preclinical models of chemotherapy-induced peripheral neuropathy. Front Immunol 2021;11:626687.
DOI: https://doi.org/10.3389/fimmu.2020.626687
Di Cesare Mannelli L, Pacini A, Corti F, Boccella S, Luongo L, Esposito E, et al. Antineuropathic profile of N-palmitoylethanolamine in a rat model of oxaliplatin-induced neurotoxicity. PLoS One 2015;10:e0128080.
DOI: https://doi.org/10.1371/journal.pone.0128080
Di Cesare Mannelli L, Pacini A, Matera C, Zanardelli M, Mello T, De Amici M, et al. Involvement of α7 nAChR subtype in rat oxaliplatin-induced neuropathy: Effects of selective activation. Neuropharmacology 2014;79:37-48.
DOI: https://doi.org/10.1016/j.neuropharm.2013.10.034
Micheli L, Mattoli L, Maidecchi A, Pacini A, Ghelardini C, Di Cesare Mannelli L. Effect of Vitis vinifera hydroalcoholic extract against oxaliplatin neurotoxicity: in vitro and in vivo evidence. Sci Rep 2018;8:14364.
DOI: https://doi.org/10.1038/s41598-018-32691-w
Shim HS, Bae C, Wang J, Lee K-H, Hankerd KM, Kim HK, et al. Peripheral and central oxidative stress in chemotherapy-induced neuropathic pain. Mol Pain 2019;15:174480691984009.
DOI: https://doi.org/10.1177/1744806919840098
Loane DJ, Kumar A. Microglia in the TBI brain: The good, the bad, and the dysregulated. Exp Neurol 2016;275:316-27.
DOI: https://doi.org/10.1016/j.expneurol.2015.08.018
Segawa S, Tatsumi N, Ohishi A, Nishida K, Nagasawa K. Characterization of zinc uptake by mouse primary cultured astrocytes and microglia. Metallomics 2015;7:1067-77.
DOI: https://doi.org/10.1039/C5MT00085H
Sun Y, Sukumaran P, Singh BB. Magnesium-induced cell survival is dependent on TRPM7 expression and function. Mol Neurobiol 2020;57:528-38.
DOI: https://doi.org/10.1007/s12035-019-01713-7
Rivas-García L, Quiles JL, Varela-López A, Arredondo M, Lopez P, Diéguez AR, et al. In vitro study of the protective effect of manganese against vanadium-mediated nuclear and mitochondrial DNA damage. Food Chem Toxicol 2020;135:110900.
DOI: https://doi.org/10.1016/j.fct.2019.110900
Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 2010;140:900-17.
DOI: https://doi.org/10.1016/j.cell.2010.02.034
Sen T, Saha P, Gupta R, Foley LM, Jiang T, Abakumova OS, et al. Aberrant ER stress induced neuronal-IFNβ elicits white matter injury due to microglial activation and T-cell infiltration after TBI. J Neurosci 2020;40:424-46.
DOI: https://doi.org/10.1523/JNEUROSCI.0718-19.2019
Hovens I, Nyakas C, Schoemaker R. A novel method for evaluating microglial activation using ionized calcium-binding adaptor protein-1 staining: cell body to cell size ratio. Neuroimmunol Neuroinflam 2014;1:82.
DOI: https://doi.org/10.4103/2347-8659.139719
Jurga AM, Paleczna M, Kuter KZ. Overview of general and discriminating markers of differential microglia phenotypes. Front Cell Neurosci 2020 6;14:198.
DOI: https://doi.org/10.3389/fncel.2020.00198
Ma Q. Role of Nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 2013;53:401-26.
DOI: https://doi.org/10.1146/annurev-pharmtox-011112-140320
Wei S-P, Jiang W-D, Wu P, Liu Y, Zeng Y-Y, Jiang J, et al. Dietary magnesium deficiency impaired intestinal structural integrity in grass carp (Ctenopharyngodon idella). Sci Rep 2018;8:12705.
DOI: https://doi.org/10.1038/s41598-018-30485-8
Simón J, Goikoetxea-Usandizaga N, Serrano-Maciá M, Fernández-Ramos D, Sáenz de Urturi D, Gruskos JJ, et al. Magnesium accumulation upon cyclin M4 silencing activates microsomal triglyceride transfer protein improving NASH. J Hepatol 2021;75:34-45.
DOI: https://doi.org/10.1016/j.jhep.2021.01.043
How to Cite
Branca, J. J., Carrino, D., Paternostro, F., Gulisano, M., Becatti, M., Di Cesare Mannelli, L., & Pacini, A. (2021). Antioxidant support to ameliorate the oxaliplatin-dependent microglial alteration: morphological and molecular study. European Journal of Histochemistry, 65(s1). https://doi.org/10.4081/ejh.2021.3285
Copyright (c) 2021 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
