Neurochemical Research

, Volume 44, Issue 9, pp 2202–2214 | Cite as

Ilex paraguariensis Attenuates Changes in Mortality, Behavioral and Biochemical Parameters Associated to Methyl Malonate or Malonate Exposure in Drosophila melanogaster

  • José Luiz Portela
  • Matheus Chimelo Bianchini
  • Aline Augusti Boligon
  • Murilo Ricardo Sigal Carriço
  • Rafael Roehrs
  • Félix Alexandre Antunes Soares
  • Marcelo Gomes de Gomes
  • Waseem Hassan
  • Robson Luiz PuntelEmail author
Original Paper


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.


Methylmalonic 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.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • José Luiz Portela
    • 1
  • Matheus Chimelo Bianchini
    • 1
  • Aline Augusti Boligon
    • 2
  • Murilo Ricardo Sigal Carriço
    • 1
  • Rafael Roehrs
    • 1
  • Félix Alexandre Antunes Soares
    • 2
  • Marcelo Gomes de Gomes
    • 1
  • Waseem Hassan
    • 3
  • Robson Luiz Puntel
    • 1
    • 4
    Email author
  1. 1.Programa de Pós-graduação Em BioquímicaUniversidade Federal Do Pampa (UNIPAMPA)UruguaianaBrazil
  2. 2.Programa de Pós-graduação Em Bioquímica Toxicológica, Departamento de Bioquímica E Biologia Molecular, Centro de Ciências Naturais E Exatas (CCNE)Universidade Federal de Santa Maria (UFSM)Santa MariaBrazil
  3. 3.Institute of Chemical SciencesUniversity of PeshawarPeshawarPakistan
  4. 4.Universidade Federal Do PampaUruguaianaBrazil

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