title: Assessment of mercury chloride-induced toxicity and the relevance of P2X7 receptor activation in zebrafish larvae.
abstract: Zebrafish (Danio rerio) has been adopted as a model for behavioral, immunological and toxicological studies. Mercury is a toxic heavy metal released into the environment. There is evidence indicating that heavy metals can modulate ionotropic receptors, including the purinergic receptor P2X7. Therefore, this study evaluated the in vivo effects of acute exposure to mercury chloride (HgCl2) in zebrafish larvae and to investigate the involvement of P2X7R in mercury-related toxicity. Larvae survival was evaluated for 24 h after exposure to HgCl2, ATP or A740003. The combination of ATP (1 mM) and HgCl2 (20 μg/L) decreased survival when compared to ATP 1 mM. The antagonist A740003 (300 and 500 nM) increased the survival time, and reversed the mortality caused by ATP and HgCl2 in association. Quantitative real time PCR showed a decrease of P2X7R expression in the larvae treated with HgCl2 (20 μg/L). Evaluating the oxidative stress our results showed decreased CAT (catalase) activity and increased MDA (malondialdehyde) levels. Of note, the combination of ATP with HgCl2 showed an additive effect. This study provides novel evidence on the possible mechanisms underlying the toxicity induced by mercury, indicating that it is able to modulate P2X7R in zebrafish larvae.
authors.affiliation: Instituto de Toxicologia e Farmacologia, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, 90619-900 Porto Alegre, RS, Brazil; Faculdade de Farmácia, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Fernanda Fernandes
authors.initials: FF
authors.lastname: Cruz
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Leite
authors.forename: Talita Carneiro Brandão
authors.initials: TC
authors.lastname: Pereira
authors.forename: Maurício Reis
authors.initials: MR
authors.lastname: Bogo
authors.forename: Carla Denise
authors.initials: CD
authors.lastname: Bonan
authors.forename: Ana Maria Oliveira
authors.initials: AM
authors.lastname: Battastini
authors.forename: Maria Martha
authors.initials: MM
authors.lastname: Campos
authors.forename: Fernanda Bueno
authors.initials: FB
authors.lastname: Morrone
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000096:biosynthesis; D005260:Female; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008627:Mercuric Chloride / Q000633:toxicity*; D018384:Oxidative Stress; D011804:Quinolines / Q000494:pharmacology; D058486:Receptors, Purinergic P2X7 / Q000096:biosynthesis / Q000378:metabolism*; D015027:Zebrafish
chemical_list: C515928:(N-(1-(((cyanoimino)(5-quinolinylamino) methyl) amino)-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide); D000081:Acetamides; D011804:Quinolines; D058486:Receptors, Purinergic P2X7; D008315:Malondialdehyde; D008627:Mercuric Chloride; D000255:Adenosine Triphosphate; D002374:Catalase
keywords: Mercury; Oxidative stress; P2X7R; Zebrafish larvae