Cytotoxicity of catechol towards human glioblastoma cells via superoxide and reactive quinones generation

Abstract

It is known that the exposure to benzene in the petroleum industry causes lympho-haematopoietic cancer among workers. However, there is little data concerning the toxicity of benzene to the central nervous system. Benzene easily penetrates the brain where it is metabolized to catechol. Since catechol autoxidizes in physiological phosphate buffer, we hypothesized that it could be toxic towards glial cells due to the generation of reactive oxygen species and quinones. In this work we studied the cytotoxic properties of catechol towards human glioblastoma cells. We found that catechol was toxic towards these cells after 72 hours and this toxicity was related to the formation of quinones. Catechol at 230µM killed 50% of cells. The catechol-induced cytotoxicity was prevented by the addition of 100U superoxide dismutase, which also inhibited the formation of quinones. These data suggest that catechol induces cytotoxicity via the extracellular generation of superoxide and quinones. Catechol Cytotoxicity 1,2-dihydroxybenzene Glioblastoma Superoxide resumo Sabe-se que a exposição de trabalhadores ao benzeno na indústria petrolífera é uma causa de câncer do sistema linfo-hematopoiético. Pouco se sabe, contudo, a respeito da toxicidade do benzeno no sistema nervoso central. O benzeno penetra facilmente no cérebro, onde é metabolizado a catecol. Como o catecol se auto-oxida em tampão fosfato no pH fisiológico, supôs-se que esse composto poderia ser tóxico para células gliais por gerar espécies reativas do oxigênio e quinonas. Nesse trabalho estudou-se a citotoxicidade do catecol para células de glioblastoma humano. O catecol foi tóxico após 72 horas e essa toxicidade relacionou-se com a formação de quinonas. O catecol a 230µM matou metade das células em cultura. A toxicidade do catecol e a produção de quinonas foram inibidas por 100U de superóxido dismutase. Esses dados sugerem que a toxicidade induzida pelo catecol deve-se à produção extracelular de superóxido e quinonas reativas. Catecol Citotoxicidade 1,2-diidroxibenzeno Glioblastoma Superóxido unitermos y key words J Bras Patol Med Lab • v. 40 • n. 4 • p. 280-5 • agosto 2004 ARTIGO ORIGINAL

The role of catechols and free radicals in benzene toxicity: An oxidative DNA damage pathway

“…Catechol can act as pro-oxidant, and as a consequence of its redox cycling activity may damage macromolecules such as DNA and proteins and destroy membrane function [Schweigert et al, 2001b]. It has been shown that catechol-induced cytotoxicity towards glioblastoma cells in vitro is because of the production of superoxide and reactive quinones [Pereira et al, 2004]. Environmental and Molecular Mutagenesis.…”

Investigation of toxic factors affecting cells of rat brains exposed to 3-methylcatechol

“…In a previous study (Pereira et al, 2004), it was demonstrated that catechol was cytotoxic to human glioblastoma cells via the production of superoxide and reactive quinones. Catechol at 230 µM killed 50% of these cells after 72 h. In another work , the neurotoxicity of apomorphine, a catechol (potent dopamine agonist), was studied.…”

Mitochondrial KATPChannel and Dopaminergic Vulnerability Neurons in Parkinson’s Disease

“…0-Quinones derived from dopamine to form aminochrome are rapidly mopped by cysteines (or other thiols present) generating forms that are oxidized to form melanotic pigments [32][33][34]. The action of flavenzyme FADH, such as DT-diaphorase induce the formation of hydroquinone and ROS from reduction of o-quinones derived of freely dopamine in the cytosol [35,36]. Semiquinone is a highly reactive radical, and under aerobic conditions, it catalyzes the reduction reaction of oxygen to the superoxide that activates the redox cycle between the leucoaminochrome o-semiquinone radical and the aminochrome [37,38].…”