P2X7R and PANX-1 channel relevance in a zebrafish larvae copper-induced inflammation model

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology Vol. 223; pp. 62 - 70
• Main Authors: de Marchi, F.O., Cruz, F.F., Menezes, F.P., Kist, L.W., Bogo, M.R., Morrone, F.B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2019
• Subjects: Acetamides - pharmacology; Animals; Connexins - antagonists & inhibitors; Connexins - genetics; Copper; Copper - toxicity; Disease Models, Animal; Female; Gene Expression Regulation - drug effects; Inflammation; Inflammation - chemically induced; Inflammation - mortality; Interleukin-10 - genetics; Interleukin-1beta - genetics; Larva - drug effects; Locomotion - drug effects; Male; Oxidative Stress; P2X7 receptor; PANX-1 channel; Probenecid - pharmacology; Purinergic P2X Receptor Antagonists - toxicity; Quinolines - pharmacology; Receptors, Purinergic P2X7 - genetics; Zebrafish; Zebrafish - genetics; Zebrafish - metabolism; Zebrafish Proteins - antagonists & inhibitors; Zebrafish Proteins - genetics; Zebrafish; Inflammation; Copper; P2X7 receptor; PANX-1 channel
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/j.cbpc.2019.05.012

Copper is a metal that participates in several essential reactions in living organisms, and it has been used as an inflammatory inducing agent in zebrafish larvae. In this study, we evaluated the effect P2X7 receptor and/or pannexin channel 1 (PANX-1) blockage in this inflammation model. To perform the experiments, 7 dpf larvae were exposed to 10 μM of copper and treated with 100 μM probenecid, PANX-1 inhibitor, and/or 300 nM A740003, a P2X7R selective antagonist. Larvae survival was assessed up to 24 h after treatments. The evaluation of larvae behavior was evaluated after acute (4 h) and chronic (24 h) exposure. The parameters of locomotor activity measured were: mobile time, average speed, distance and turn angle. We analyzed the gene expression of the P2X7 receptor, PANX1a and PANX1b channels and interleukins IL-10 and IL-1b after 24 h of treatment. Treatments did not decrease larval survival in the time interval studied. Changes in larvae locomotion were observed after the longest time of exposure to copper and the treatment with probenecid was able to reverse part of the effects caused by copper. No significant difference was observed in the oxidative stress assays and probenecid and copper treatment decrease partially PANX1a gene expression groups. The data presented herein shows the relevance of the blockage of P2X7-PANX-1 in copper-induced inflammation. [Display omitted] •Copper exposure for 24 h altered zebrafish larvae locomotor activity.•PANX1 channel inhibitor reversed the effect of copper on the larvae locomotion.•Larvae treated with probenecid showed PANX1a channel expression decreased.•Copper did not alter IL-1β and IL-10 gene expression nor oxidative stress markers.