Involvement of purinergic system in inflammation and toxicity induced by copper in zebrafish larvae

Autor: Talita Carneiro Brandão Pereira, Maurício Reis Bogo, Maria M. Campos, Lucas de Oliveira Maboni, Fernanda Francine Zimmermann, Fernanda Fernandes Cruz, Ana Maria Oliveira Battastini, Fernanda Bueno Morrone, Carla Denise Bonan, Carlos Eduardo Leite, Denis B. Rosemberg
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Repositório Institucional PUCRS
Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
instacron:PUC_RS
Popis: The use of zebrafish (Danio rerio) is increasing as an intermediate preclinical model, to prioritize drug candidates for mammalian testing. As the immune system of the zebrafish is quite similar to that of mammals, models of inflammation are being developed for the screening of new drugs. The characterization of these models is crucial for studies that seek for mechanisms of action and specific pharmacological targets. It is well known that copper is a metal that induces damage and cell migration to hair cells of lateral line of zebrafish. Extracellular nucleotides/nucleosides, as ATP and adenosine (ADO), act as endogenous signaling molecules during tissue damage by exerting effects on inflammatory and immune responses. The present study aimed to characterize the inflammatory status, and to investigate the involvement of the purinergic system in copper-induced inflammation in zebrafish larvae. Fishes of 7 days post-fertilization were exposed to 10 μM of copper for a period of 24 h. The grade of oxidative stress, inflammatory status, copper uptake, the activity and the gene expression of the enzymes responsible for controlling the levels of nucleotides and adenosine were evaluated. Due to the copper accumulation in zebrafish larvae tissues, the damage and oxidative stress were exacerbated over time, resulting in an inflammatory process involving IL-1β, TNF-α, COX-2 and PGE2. Within the purinergic system, the mechanisms that control the ADO levels were the most involved, mainly the reactions performed by the isoenzyme ADA 2. In conclusion, our data shed new lights on the mechanisms related to copper-induced inflammation in zebrafish larvae.
Databáze: OpenAIRE