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

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)89-97
Number of pages9
JournalArchives of Toxicology
Volume84
Issue number2
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

Rutin
Mitochondria
Quercetin
Glycosides
Rats
Reactive Oxygen Species
Brain
Derivatives
Toxicity
Neuroprotective Agents
Flavonoids
Lipid Peroxidation
Antioxidants
Lipids
Animal Disease Models
Oxidative stress
Chelation
Blood-Brain Barrier
Animals
Oxidative Stress

Keywords

  • MeHg toxicity
  • Mitochondria
  • Quercetin
  • Quercitrin
  • ROS
  • Rutin

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Comparative study of quercetin and its two glycoside derivatives quercitrin and rutin against methylmercury (MeHg)-induced ROS production in rat brain slices. / Wagner, Caroline; Vargas, Alessandra P.; Roos, Daniel H.; Morel, Ademir F.; Farina, Marcelo; Nogueira, Cristina W.; Aschner, Michael; Rocha, João B.

In: Archives of Toxicology, Vol. 84, No. 2, 2010, p. 89-97.

Research output: Contribution to journalArticle

Wagner, Caroline ; Vargas, Alessandra P. ; Roos, Daniel H. ; Morel, Ademir F. ; Farina, Marcelo ; Nogueira, Cristina W. ; Aschner, Michael ; Rocha, João B. / Comparative study of quercetin and its two glycoside derivatives quercitrin and rutin against methylmercury (MeHg)-induced ROS production in rat brain slices. In: Archives of Toxicology. 2010 ; Vol. 84, No. 2. pp. 89-97.
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