Ilex paraguariensis Attenuates Changes in Mortality, Behavioral and Biochemical Parameters Associated to Methyl Malonate or Malonate Exposure in Drosophila melanogaster
Methylmalonic acidemia is a genetic disease characterized by accumulation of organic acids, such as methylmalonic (MMA) and malonic (MA) acids. Considering that the accumulation of MMA and MA causes several damages due to oxidative stress, antioxidants are thought to play a pivotal role in preventing deleterious effects associated with exposure to such compounds. Ilex paraguariensis (IP) was used here to test the hypothesis that supplementation with the aqueous extract of this plant could exert protective effect against MMA or MA induced mortality, behavioral and/or biochemical changes in Drosophila melanogaster (DM). Initially, a curve time- and dose–response to MMA (1–10 mM), MA (1–10 mM) and IP (63–500 μM) was performed. Thereafter, flies were concomitantly exposed to MA (5 mM), MMA (5 mM) and/or IP (250 μg/mL) during 15 days for survival assay, and for 48 hs to MA (1 or 5 mM), MMA (1 or 5 mM) and/or IP (250 μg/mL) for subsequent investigations. Both MMA and MA exposure resulted in higher incidence of mortality, a worse performance in the negative geotaxis assay and increased locomotion in open-field test as compared with control group. Furthermore, a marked increase in non-protein thiol (NPSH) and in thiobarbituric acid reactive substances (TBARS) levels, decrease in superoxide dismutase (SOD), catalase and acetylcholinesterase (AChE) activities, and decrease in MTT and resazurin reduction were noted in MMA or MA treated groups. IP treatment offered significant protection against all alterations associated to MMA or MA exposure. This study confirm the hypothesis that supplementation with IP offers protection against changes associated to MMA or MA exposure in DM, due, at least in part, to its antioxidant effect.
KeywordsMethylmalonic acid Malonic acid Ilex paraguariensis Drosophila Oxidative stress
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. The authors are also grateful to FAPERGS, CNPq, FINEP, INCT-EN and UNIPAMPA. Additional support was given by CNPq/FAPERGS/DECIT/SCTIE-MS/PRONEM #16/2551-0000248-7, CNPq (Universal) research grant #449428/2014-1 and CNPq scholarship (#301807/2018-3).
Compliance with Ethical Standards
Conflict of interest
The authors declare that there is no conflict of interest.
- 1.Panigrahi I, Bhunwal S, Varma H, Singh S (2017) Methylmalonic acidemia with novel MUT gene mutations. Case Rep Genet 2017:8984951Google Scholar
- 11.Portela JL, Soares D, Rosa H, Roos DH, Pinton S, Avila DS, Puntel RL (2017) Ilex paraguariensis crude extract acts on protection and reversion from damage induced by t-butyl hydroperoxide in human erythrocytes: a comparative study with isolated caffeic and/or chlorogenic acids. J Sci Food Agric 97:2007–2014CrossRefGoogle Scholar
- 13.Courtes AA, Arantes LP, Barcelos RP, da Silva IK, Boligon AA, Athayde ML, Puntel RL, Soares FA (2015) Protective effects of aqueous extract of Luehea divaricata against behavioral and oxidative changes induced by 3-nitropropionic acid in rats. Evid Complement Altern Med 2015:723431Google Scholar
- 15.Colpo AC, Rosa H, Lima ME, Pazzini CE, de Camargo VB, Bassante FE, Puntel R, Avila DS, Mendez A, Folmer V (2016) Yerba mate (Ilex paraguariensis St. Hill.)-based beverages: how successive extraction influences the extract composition and its capacity to chelate iron and scavenge free radicals. Food Chem 209:185–195CrossRefGoogle Scholar
- 20.Fernandes CEF, Scapinello J, Bohn A, Boligon AA, Athayde ML, Magro JD, Palliga M, Oliveira JV, Tres MV (2017) Phytochemical profile, antioxidant and antimicrobial activity of extracts obtained from erva-mate (Ilex paraguariensis) fruit using compressed propane and supercritical CO2. J Food Sci Technol 54:98–104CrossRefGoogle Scholar
- 22.Bianchini MC, Gularte COA, Nogara PA, Krum BN, Gayer MC, Bridi JC, Roos DH, Roehrs R, Fachinetto R, Pinton S, Avila DS, Hirth F, Rocha JBT, Puntel RL (2019) Thimerosal inhibits Drosophila melanogaster tyrosine hydroxylase (DmTyrH) leading to changes in dopamine levels and impaired motor behavior: implications for neurotoxicity. Metallomics 11:362–374CrossRefGoogle Scholar
- 26.Soares DCS, Portela JLR, Roos DH, Rodrigues NR, Gomes KK, Macedo GE, Posser T, Franco JL, Hassan W, Puntel RL (2018) Treatment with pentylenetetrazole (PTZ) and 4-aminopyridine (4-AP) differently affects survival, locomotor activity, and biochemical markers in Drosophila melanogaster. Mol Cell Biochem 442:129–142CrossRefGoogle Scholar
- 27.Araujo SM, de Paula MT, Poetini MR, Meichtry L, Bortolotto VC, Zarzecki MS, Jesse CR, Prigol M (2015) Effectiveness of gamma-oryzanol in reducing neuromotor deficits, dopamine depletion and oxidative stress in a Drosophila melanogaster model of Parkinson's disease induced by rotenone. Neurotoxicology 51:96–105CrossRefGoogle Scholar
- 29.Gabbi P, Ribeiro LR, Jessie Martins G, Cardoso AS, Haupental F, Rodrigues FS, Machado AK, Sperotto Brum J, Medeiros Frescura Duarte MM, Schetinger MR, da Cruz IB, Flavia Furian A, Oliveira MS, Dos Santos AR, Royes LF, Fighera MR, de Freitas ML (2017) Methylmalonate induces inflammatory and apoptotic potential: a link to glial activation and neurological dysfunction. J Neuropathol Exp Neurol 76:160–178CrossRefGoogle Scholar
- 30.Valdeolivas S, Pazos MR, Bisogno T, Piscitelli F, Iannotti FA, Allara M, Sagredo O, Di Marzo V, Fernandez-Ruiz J (2013) The inhibition of 2-arachidonoyl-glycerol (2-AG) biosynthesis, rather than enhancing striatal damage, protects striatal neurons from malonate-induced death: a potential role of cyclooxygenase-2-dependent metabolism of 2-AG. Cell Death Dis 4:e862CrossRefGoogle Scholar
- 40.Branco Cdos S, Scola G, Rodrigues AD, Cesio V, Laprovitera M, Heinzen H, Dos Santos MT, Fank B, de Freitas SC, Coitinho AS, Salvador M (2013) Anticonvulsant, neuroprotective and behavioral effects of organic and conventional yerba mate (Ilex paraguariensis St. Hil.) on pentylenetetrazol-induced seizures in Wistar rats. Brain Res Bull 92:60–68CrossRefGoogle Scholar