Structure-activity relationship of flavonoids derived from medicinal plants in preventing methylmercury-induced mitochondrial dysfunction

Jeferson L. Franco, Thais Posser, Fabiana Missau, Moacir G. Pizzolatti, Adair R.S. Santos, Diogo O. Souza, Michael Aschner, João B.T. Rocha, Alcir L. Dafre, Marcelo Farina

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

In the present study, we investigated the potential protective effects of three flavonoids (myricetin, myricitrin and rutin) derived from medicinal plants against methyl mercury (MeHg)-induced mitochondrial dysfunction in vitro. Incubation of mouse brain mitochondria with MeHg induced a significant decrease in mitochondrial function, which was correlated with decreased glutathione (GSH) levels and increased generation of reactive oxygen species (ROS) and lipid peroxidation. The co-incubation of mouse brain mitochondria with myricetin or myricitrin caused a concentration-dependent decrease of MeHg-induced mitochondrial dysfunction and oxidative stress. The flavonoid rutin was ineffective in counteracting MeHg toxicity. Among the three tested flavonoids, myricetin was the most efficient in protecting against MeHg-induced mitochondrial dysfunction. Moreover, myricetin completely blocked MeHg-induced ROS formation and lipid peroxidation and partially prevented MeHg-induced GSH depletion. The ability of myricetin to attenuate MeHg-induced mitochondrial dysfunction and oxidative stress appears to be related to its higher scavenging capability when compared to myricitrin and rutin. Overall, the results suggest that MeHg-induced mitotoxicity is associated with oxidative stress. The ability of myricetin to prevent MeHg-induced oxidative damage in brain mitochondria renders this flavonoid a promising molecule for further in vivo studies in the search for potential antidotes to counteract MeHg-induced neurotoxicity.

Original languageEnglish (US)
Pages (from-to)272-278
Number of pages7
JournalEnvironmental Toxicology and Pharmacology
Volume30
Issue number3
DOIs
StatePublished - Nov 2010

Keywords

  • Flavonoids
  • Methylmercury
  • Mitochondria
  • Myricetin
  • Toxicity

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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    Franco, J. L., Posser, T., Missau, F., Pizzolatti, M. G., Santos, A. R. S., Souza, D. O., Aschner, M., Rocha, J. B. T., Dafre, A. L., & Farina, M. (2010). Structure-activity relationship of flavonoids derived from medicinal plants in preventing methylmercury-induced mitochondrial dysfunction. Environmental Toxicology and Pharmacology, 30(3), 272-278. https://doi.org/10.1016/j.etap.2010.07.003