title: Superoxide anion generation and oxidative stress in methylmercury-induced endothelial toxicity in vitro.
abstract: Emerging evidence has pointed to mercury exposure as a risk factor for hypertension, atherosclerosis, myocardial infarction and coronary heart disease. However, the underlying mechanisms are not well understood. This study investigated potential toxic effects of low concentrations of methylmercury (MeHg) in cultured bovine aortic endothelial cells (BAECs) and the possible involvement of reactive species, particularly superoxide anion, in mediating such toxicity. MeHg treatment increased the oxidation of 2',7'-dichlorodihydrofluorescein diacetate (a general probe for reactive species) and dihydroethidium, a specific probe for superoxide anion. MeHg-induced 2',7'-dichlorodihydrofluorescein diacetate and dihydroethidium oxidations were significantly decreased by apocynin, an inhibitor of the enzyme NADPH oxidase, which represents a main source of superoxide anion in endothelial cells. MeHg treatment significantly disrupted mitochondrial membrane potential and this event was also reversed by apocynin. MeHg treatment also decreased glutathione levels and this event preceded glutathione peroxidase inhibition, which was observed only at 24h after treatment. These results indicate that MeHg induces oxidative stress in cultured BAECs and that this event is related to the production of superoxide anion. Moreover, the observed protective effects of apocynin in BAECs suggest the potential involvement of NADPH-oxidase in MeHg-induced endothelial dysfunction, which represents a pivotal event in most cardiovascular diseases.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Heloisa
authors.initials: H
authors.lastname: Ghizoni
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Viviane
authors.initials: V
authors.lastname: de Souza
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Marcos Raniel
authors.initials: MR
authors.lastname: Straliotto
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Andreza Fabro
authors.initials: AF
authors.lastname: de Bem
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: marcelo.farina@ufsc.br.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil. Electronic address: marianaappel@gmail.com.
authors.forename: Mariana Appel
authors.initials: MA
authors.lastname: Hort
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008767:Methylmercury Compounds / Q000633:toxicity*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D008767:Methylmercury Compounds; D013481:Superoxides; C056165:acetovanillone; D005979:Glutathione Peroxidase; D019255:NADPH Oxidases; D005978:Glutathione
keywords: Cardiovascular; Endothelial cells; Methylmercury; Oxidative stress; Superoxide