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

被引:61
作者
Franco, Jeferson L. [1 ,5 ]
Posser, Thais [1 ,4 ]
Missau, Fabiana [3 ]
Pizzolatti, Moacir G. [3 ]
Santos, Adair R. S. [2 ]
Souza, Diogo O. [6 ]
Aschner, Michael [7 ]
Rocha, Joao B. T. [4 ]
Dafre, Alcir L. [1 ]
Farina, Marcelo [1 ]
机构
[1] Univ Fed Santa Catarina, Dept Bioquim, Ctr Ciencias Biol, BR-88040900 Florianopolis, SC, Brazil
[2] Univ Fed Santa Catarina, Dept Ciencias Fisiol, Ctr Ciencias Biol, BR-88040900 Florianopolis, SC, Brazil
[3] Univ Fed Santa Catarina, Dept Quim, Ctr Ciencias Fis & Matemat, BR-88040900 Florianopolis, SC, Brazil
[4] Univ Fed Santa Maria, Dept Quim, Ctr Ciencias Nat & Exatas, BR-97119900 Santa Maria, RS, Brazil
[5] Univ Fed Pampa, Sao Gabriel, RS, Brazil
[6] Univ Fed Rio Grande do Sul, Dept Bioquim, Inst Ciencias Basicas Saude, Porto Alegre, RS, Brazil
[7] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA
基金
美国国家卫生研究院;
关键词
Methylmercury; Toxicity; Mitochondria; Flavonoids; Myricetin; 2,3-DIMERCAPTO-1-PROPANESULFONIC ACID DMPS; MERCURY-INDUCED NEUROTOXICITY; OXIDATIVE STRESS; ANTIOXIDANT ACTIVITY; EXPOSURE; GLUTATHIONE; TRANSPORT; INHIBITION; GLUTAMATE; TOXICITY;
D O I
10.1016/j.etap.2010.07.003
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
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. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:272 / 278
页数:7
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