Resveratrol protects against copper and iron toxicity in Drosophila melanogaster
Main Article Content
Copper (Cu) and iron (Fe) are essential trace elements that when in excess are capable of causing cytotoxic effects leading to lipid peroxidation and promoting oxidative stress. Resveratrol (RES) is a natural polyphenol with antioxidant and anti-inflammatory properties. This study was carried out to evaluate the protective role of RES in Fe and Cu sulphate-induced oxidative stress in Drosophila melanogaster.
Adult wild type flies were fed Cu2+ and Fe2+ (1 mM each) and/or RES (30 and 60 mg/kg diet) for 7 days. Survival, negative geotaxis and emergence rate were evaluated by daily recording of fruit fly mortality and final analysis. Fruit flies were anaesthetized using CO2 gas, homogenized and centrifuged at 4,000 rpm for 10 minutes at 4 °C. Aliquots of the supernatants were used for the estimation of biochemical markers using spectrophotometry.
Fruit flies co-treated with FeSO4 + CuSO4 (1 mM each) + RES (30 and 60 mg/Kg) significantly elevated H2O2, NO, lipid peroxidation, acetylcholinesterase as well as GSH, GST, catalase and total thiols (p<0.05) compared with the Cu2+ + Fe2+ (1mM each) treated group. Flies co-treated with FeSO4 + CuSO4 (1mM each) + RES (30 and 60mg/Kg) also had significantly improved (p< 0.05) eclosion and climbing rates compared with the Cu2+ + Fe2+ (1mM each) treated group.
This study demonstrated that RES reduced Cu2+ and Fe2+-induced radical generation in D. melanogaster and improved the antioxidant buffering capability of the flies. Therefore, RES could be used in management of disorders involving oxidative stress.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The journal allows the authors to hold the copyright without restrictions and allow the authors to retain publishing rights without restrictions.
Pavelková M, Vysloužil J, Kubová K, Vetchý D. Biologická role mìdi jako základního stopového prvku v lidském organismu. [Biological role of copper as an essential trace element in the human organism]. Ceska Slov Farm 2018;67:143-53.Czech.
Dusek P, Litwin T, Czlonkowska A. Wilson disease and other neurodegenerations with metal accumulations. Neuro Clin 2015;33: 175–204. doi: 10.1016/j.ncl.2014.09.006 .
Lone AA, Ganai SA, Ahanger RA, Bhat HA, Bhat TA, Wani IA. Free radicals and antioxidants: myths, facts and mysteries. Afr J Pure Appl Chem 2013;7:91–113. DOI: 10.5897/AJPAC12.074.
Southon A, Burke S, Camakaris R. What can flies tell us about copper homeostasis? Metallomics 2013;5:1346–56. DOI: 10.1039/c3mt00105a.
Engwa GA, Ferdinand PU, Nwalo FN, Unachukwu MN. Mechanism and health effects of heavy metal toxicity in humans. In: Karcýoðlu O, Arslan B. Poisoning in the modern world - new tricks for an old dog? Intechopen;2019.pp.70-90. DOI: 10.5772/intechopen.82511.
Valko M, Jomova K, Rhodes CJ, Kuca K, Musílek K. Redox-and non-redox-metal-induced formation of free radicals and their role in human disease. Arch Toxicol 2016;90:1-37. doi: 10.1007/s00204-015-1579-5.
Aschner M. Copper in the human body. Scholarly Community Encyclopedia; 2021.
Pastor RF, Restani P, Di Lorenzo C, et al. Resveratrol, human health and winemaking perspectives. Crit Rev Food Sci Nutr 2019;59: 1237–55. DOI: 10.1080/10408398.2017. 1400517.
Yeh CB, Hsieh MJ, Lin CW, et al. Correction: The antimetastatic effects of resveratrol on hepatocellular carcinoma through the downregulation of a metastasis-associated protease by SP-1 modulation. PLoS ONE 2017;12:e0174494. https://doi.org/10.1371/journal.pone.0174494.
Li J, Wang S, Duan J, et al. The protective mechanism of resveratrol against hepatic injury induced by iron overload in mice. Toxicol Appl Pharmacol 2021;424:115596. doi: 10.1016/j.taap.2021.115596.
Jovicicì A, Mertens J, Boeynaems S, et al. Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS. Nat Neurosci 2015;18:1226-9. DOI: https://doi.org/10.1038/nn.4085.
Becker LA, Huang B, Bieri G, et al. Therapeutic reduction of ataxin 2 extends lifespan and reduces pathology in TDP-43 mice. Nature 2017;544:367-71. DOI: https://doi.org/10.1038/nature22038.
Pizzino G, Irrera N, Cucinotta M, et al. Oxidative stress: harms and benefits for human health. Oxid Med Cell Longev 2017, Article ID 8416763, 13 pages. https://doi.org/10.1155/2017/8416763.
Abolaji AO, Fasae KD, Iwezor CE, Aschner M, Farombi EO. Curcumin attenuates copper-induced oxidative stress and neurotoxicity in Drosophila melanogaster. Toxicol Rep 2020;7:261–8. DOI: https://doi.org/10.1016/j.toxrep.2020.01.01.
Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121–6.
Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7:88–95.
Wolff SP. Ferrous ion oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Meth Enzymol 1994;233:182–9.
Habig WH, Jakoby WB. Assays for differentiation of glutathione-S-transferases. Meth Enzymol 1981;77:398–405.
Vashney R, Kale RK. Effects of calmodulin antagonist. Int J Radiat Biol 1990;58:733-73.
Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1993;61:882–90.
Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR. Bromobenzene induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as a hepatotoxic metabolite. Pharmacol 1974;1: 151–69.
Abolaji AO, Kamdem JP, Lugokenski TH, et al. Ovotoxicants 4-vinylcyclohexene 1, 2-monoepoxide and 4 vinylcyclohexene diepoxide disrupt redox status and modify different electrophile sensitive target enzymes and genes in Drosophila melanogaster. Redox Biol 2015;5:328–39.
Rajendran P, Rengarajan T, Thangavel J, et al. The vascular endothelium and human diseases. Int J Biol Sci 2013;9:1057–69.
Konyalioglu S, Armagan G, Yalcin A, Atalayin C, Dagci T. Effects of resveratrol on hydrogen peroxide-induced oxidative stress in embryonic neural stem cells. Neural Regen 2013;8:485–95. DOI: 10.3969/j.issn.1673-5374.2013.06.001.
Rege SD, Geetha T, Broderick TL, Babu JR. Resveratrol protects a amyloid-induced oxidative damage and memory associated proteins in H19-7 hippocampal neuronal cells. Curr Alzheimer Res 2015;12:147–56. DOI: 10.2174/1567205012666150204130009.
Dasari S, Ganjayi MS, Oruganti L, Balaji H, Meriga B. Glutathione S-transferases detoxify endogenous and exogenous toxic agents - mini review. J Dairy Vet Anim Res 2017;5:157 9.
Zhao D, Shah NP, Concomitant ingestion of lactic acid bacteria and black tea synergistically enhances flavonoid bioavailability and attenuates D-galactose-induced oxidative stress in mice via modulating glutathione antioxidant system. J Nutr Biochem 2016;38:116–24. DOI: 10.1016 /j.jnutbio.2016.09.005.
Comba A, Gureser AS, Karasartova D, Senat A, Erel O, Ozkan AT. Thiol-disulfide homeostasis in children with celiac disease. Pediatr Int 2020;10:111-43. DOI: 10.1111/ped.14243.
Farkhondeh T, Folgado SL, Pourbagher-Shahri AM, Ashrafizadeh M, Samarghandian S. The therapeutic effect of resveratrol: focusing on the Nrf2 signaling pathway. Biomedicine Pharmacotherapy 2020;127: 110234, https://doi.org/10.1016/j.biopha.2020. 110234.
Li XN, Ma LY, Ji H, Qin YH, Jin SS, Xu LX. Resveratrol protects against oxidative stress by activating the Keap 1/Nrf2 antioxidant defense system in obese asthmatic rats. Exp Ther Med 2018;16:4339-48. DOI: 10.3892/etm.2018.6747
Adedara AO, Babalola AD, Stephano F, et al. An assessment of the rescue action of resveratrol in parkin loss of function-induced oxidative stress in Drosophila melanogaster. Sci Rep 2022;12:3922. https://doi.org/10.1038/s41598-022-07909-7.
Man AWC, Li H, Xia N. The role of sirtuin1 in regulating endothelial function, arterial remodeling and vascular aging. Front Physiol 2019;10:1173. doi: 10.3389/fphys.2019.01173.
Oh YS, Jun HS. Role of bioactive food components in diabetes prevention: effects on beta-cell function and preservation. Nutrition Metabolic Insights 2014;7:51–59. doi:10.4137/NMI.S13589.
Chen ML, Yi L, Jin X, et al. Resveratrol attenuates vascular endothelial inflammation by inducing autophagy through the cAMP signaling pathway. Autophagy 2013;9:2033–45. DOI: 10.4161/auto.26336.
Frozza RL, Bernardi A, Hoppe JB, et al. Lipid-core nanocapsules improve the effects of resveratrol against Abeta-induced neuroinflammation. J Biomed Nanotech 2013;9:2086–104. DOI: 10.1166/jbn.2013. 1709.
Iwasaki K, Ray PD, Huang BW, Sakamoto K, Kobayashi T, Tsuji Y. Role of AMP-activated protein kinase in ferritin H gene expression by resveratrol in human T cells. Biochemistry 2013;52:5075-83. doi: 10.1021/bi400399f.