Involvement of purinergic system in inflammation and toxicity induced by copper in zebrafish larvae.
Toxicol Appl Pharmacol
; 272(3): 681-9, 2013 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-23933163
ABSTRACT
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-1ß, 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.
Palavras-chave
ADA; ADO; ADP; AMP; ATP; Adenosine; CAT; COX-2; Copper; DAD; Diode array detector; E-NTPDase; Ecto-5'-NT; GSH; HPLC-FLD; ICP-MS; IL-10; IL-1ß; INO; Inductively coupled plasma mass spectrometry; Inflammation; Inosine; Interleukin 10; Interleukin 1ß; MPO; Myeloperoxidase; NO; Nitric oxide; PGE(2); Prostaglandin E(2); Purinergic system; SOD; Superoxide dismutase; TNF-α; Tumor necrosis factor α; UHPLC; Ultra high performance liquid chromatography coupled with mass spectrometry; Zebrafish; adenosine; adenosine deaminase; adenosine diphosphate; adenosine monophosphate; adenosine triphosphate; catalase; cyclooxygenase 2; ecto-5'-nucleotidase; ecto-nucleoside-trifosfo difosfoidrolases; high performance liquid chromatography with fluorescence detector; reduced glutathione
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nucleosídeos de Purina
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Nucleotídeos de Purina
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Estresse Oxidativo
/
Cobre
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article