Mercurial-Induced Hydrogen Peroxide Generation in Mouse Brain Mitochondria: Protective Effects of Quercetin

Abstract

Plants of the genus Polygala have been shown to possess protective effects against neuronal death and cognitive impairments in neurodegenerative disorders related to excitotoxicity. Moreover, previous reports from our group have shown the neuroprotective effects of the plant Polygala paniculata against methylmercury (MeHg)-induced neurotoxicity. In this work, we have examined the potential protective effects of three compounds (7-prenyloxy-6-methoxycoumarin, quercetin, and 1,5-dihidroxi-2,3-dimethoxy xanthone) from Polygala species against MeHg- and mercuric chloride (HgCl2)-induced disruption of mitochondrial function under in vitro conditions using mitochondrial-enriched fractions from mouse brain. MeHg and HgCl2 (10-100 microM) significantly decreased mitochondrial viability; this phenomenon was positively correlated to mercurial-induced glutathione oxidation. Among the isolated compounds, only quercetin (100-300 microM) prevented mercurial-induced disruption of mitochondrial viability. Moreover, quercetin, which did not display any chelating effect on MeHg or HgCl2, prevented mercurial-induced glutathione oxidation. The present results suggest that the protective effects of quercetin against mercurial-induced mitochondrial dysfunction is related to the removal of oxidant species generated in the presence of either MeHg or HgCl2. Reinforcing this hypothesis, MeHg and HgCl2 increased the production of hydrogen peroxide in the brain mitochondria, as well as the levels of malondialdehyde. These oxidative phenomena were prevented by co-incubation with quercetin or catalase. These results are the first to show the involvement of hydrogen peroxide as a crucial molecule related to the toxic effects of both organic and inorganic mercurials in brain mitochondria. In addition, the study is the first to show the protective effect of quercetin against mercurial-induced toxicity, pointing to its capability to counteract mercurial-dependent hydrogen peroxide generation as a potential molecular mechanism of protection. Taken together, these data render quercetin a promising molecule for pharmacological studies with respects to mercurials' poisoning.

Mercury Toxicity and Neurodegenerative Effects

“…Studies on the neurotoxicity induced by MeHg have described the following phenomena: depletion of intracellular antioxidants (Franco et al 2007 ;Johansson et al 2007 ), inhibition of specifi c enzymes (Rocha et al 1993 ;Franco et al 2009 ;Wagner et al 2010 ) and modulation of transporter or neuromodulator activities of receptors (Fitsanakis and Aschner 2005 ;Yin et al 2007 ).…”

Dechampsia Antarctica Crude Extract Protects Against Hg(Ii) Induced Toxicity in Drosophila Melanogaster

“…us, compounds that possess antioxidant activity may be potential candidates in the treatment of mercury poisoning. Studies in literature have shown that plant extracts and natural compounds are able to block the toxic actions of mercury in animal models (Farina et al, 2005;Franco et al, 2007). (Betina et al, 2009).…”

Avaliação dos efeitos tóxicos resultantes da exposição crônica a baixas doses de chumbo e metilmercúrio, associados ou não, e do possível efeito protetor da niacina diante desta exposição

“…Além disso, o cérebro possui uma grande proporção de lipídeos insaturados que o torna mais susceptível à peroxidação (Kidd, 1997;Villeda-Hernández et al, 2001). Um possível mecanismo que explica a peroxidação lipídica observada no cérebro dos animais expostos ao MeHg envolve o aumento na concentração de peróxido de hidrogênio (H 2 O 2 ) devido a exposição a este metal (Franco et al, 2007). Embora seja reconhecido que o H 2 O 2 tenha um importante papel fisiológico modulando funções celulares (Droge & Droge, 2002), concentrações elevadas deste composto são perigosas para as células, principalmente devido a formação de radicais hidroxila via reação de Fenton (McCord & Day, 1978).…”