Purinergic signaling as a potential target of hypoxia stress-induced impairment of the immune system in freshwater catfish Lophiosilurus alexandri

Purinergic signaling plays an important role in the immune and inflammatory responses through the hydrolysis of adenine nucleotides, such as adenosine triphosphate (ATP), and nucleosides, such as adenosine, which are involved in physiological and pathological events as pro-inflammatory and anti-inflammatory mediators. The aim of this study was to evaluate whether purinergic signaling can modulate the immune and inflammatory responses in the plasma of Lophiosilurus alexandri exposed to hypoxia. Plasma ectonucleoside triphosphate diphosphohydrolase (NTPDase) activity using ATP as a substrate decreased after 24 and 72 h of hypoxia exposure compared with the normoxia group, while no difference was observed for NTPDase (using ADP as a substrate) and 5′-nucleotidase activities. On the other hand, adenosine deaminase (ADA) activity increased after 24 and 72 h of hypoxia exposure compared with the normoxia group. Moreover, is important to emphasize that enzymatic activity of NTPDase (using ATP as a substrate) and ADA did return to control levels only after a 72 h recovery period. Also, plasmatic levels of pro-inflammatory cytokines (interleukin-1, interleukin-6 and tumor necrosis factor-alpha) and ATP increased after 24 and 72 h of hypoxia exposure compared with the normoxia group. Based on this evidence, our findings reveal that adenine nucleotide hydrolysis is not able to modulate the immune and inflammatory responses of fish exposed to hypoxia stress. Moreover, the downregulation of plasma NTPDase activity develops a pro-inflammatory profile due to the excessive ATP content in the extracellular medium elicited by interaction with the P2X7 purineceptor. In summary, purinergic signaling displays a pro-inflammatory profile in the plasma of L. alexandri exposed to hypoxia.