Archives of Toxicology

, Volume 84, Issue 2, pp 89–97 | Cite as

Comparative study of quercetin and its two glycoside derivatives quercitrin and rutin against methylmercury (MeHg)-induced ROS production in rat brain slices

  • Caroline Wagner
  • Alessandra P. Vargas
  • Daniel H. Roos
  • Ademir F. Morel
  • Marcelo Farina
  • Cristina W. Nogueira
  • Michael Aschner
  • João B. Rocha
Inorganic Compounds


The hypothesis that methylmercury (MeHg) potently induces formation of reactive oxygen species (ROS) in the brain is supported by observations on the neuroprotective effects of various classes of antioxidants. Flavonoids have been reported to possess divalent metal chelating properties, antioxidant activities and to readily permeate the blood–brain barrier. They can also provide neuroprotection in a wide array of cellular and animal models of neurological diseases. Paradoxically, in vivo administration of quercetin displays unexpected synergistic neurotoxic effect with MeHg. Considering this controversy and the limited data on the interaction of MeHg with other flavonoids, the potential protective effect of quercetin and two of its glycoside analogs (i.e., rutin and quercitrin) against MeHg toxicity were evaluated in rat cortical brain slices. MeHg (100 μM) caused lipid peroxidation and ROS generation. Quercitrin (10 μg/mL) and quercetin (10 μg/mL) protected mitochondria from MeHg (5 μM)-induced changes. In contrast, rutin did not afford a significant protective effect against MeHg (100 μM)-induced lipid peroxidation and ROS production in cortical brain slices. MeHg-generated ROS in cortical slices was dependent upon an increase in intracellular Ca2+ levels, because the over-production of MeHg-induced H2O2 in mitochondria occurred with a concomitant increase in Ca2+ transient. Here, we have extended the characterization of mechanisms associated with the neuroprotective effects of quercetin against MeHg-induced toxicity in isolated mitochondria, by performing an array of parallel studies in brain slices. We provide novel data establishing that (1) Ca2+ plays a central role in MeHg toxicity and (2) in brain slices MeHg induces mitochondrial oxidative stress both via direct interaction with mitochondria (as previously reported in in vitro studies) as well as via mitochondria-independent (or indirect) mechanisms.


MeHg toxicity Quercetin Quercitrin Rutin ROS Mitochondria 

Supplementary material

204_2009_482_MOESM1_ESM.doc (34 kb)
Supplementary material 1 (DOC 34 kb)


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Caroline Wagner
    • 1
  • Alessandra P. Vargas
    • 1
  • Daniel H. Roos
    • 1
  • Ademir F. Morel
    • 1
  • Marcelo Farina
    • 2
  • Cristina W. Nogueira
    • 1
  • Michael Aschner
    • 3
  • João B. Rocha
    • 1
  1. 1.Centro de Ciências Naturais e Exatas, Departamento de QuímicaUniversidade Federal de Santa MariaSanta MariaBrazil
  2. 2.Departamento de Bioquímica, Centro de Ciências BiológicasUniversidade Federal de FlorianópolisFlorianópolisBrazil
  3. 3.Department of Pediatrics and PharmacologyVanderbilt University School of MedicineNashvilleUSA

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