Purinergic signaling is linked to neurodegenerative and proinflammatory damage during pathological conditions such as
hypoxia, but involvement of this pathway in brain damage in fish exposed to environmental
hypoxia remains unknown, and we propose dietary supplementation with
caffeine in order to improve the immune response. Therefore, the aim of the study was to evaluate whether the enzymatic purinergic signaling pathway is associated with inflammatory brain damage in Nile tilapia (Oreochromis niloticus) exposed to environmental
hypoxia and whether dietary supplementation with
caffeine (5% and 8%) can prevent these changes in purinergic signaling. Animals were randomly divided into six groups (A-F, n = 6 per group, in triplicate), as follows: groups A-C were submitted to normoxia, while groups D-F were submitted to
hypoxia. Groups A and D received the basal diet, while groups B and D and groups C and F received a diet containing 5% and 8%
caffeine, respectively, and fed with their respective diets for 21 days. After 21 days, aeration was disconnected (groups D-F) and the dissolved
oxygen levels were maintained as follows: group A (6.55 ± 0.23 mg/L), group B (6.51 ± 0.24 mg/L), group C (6.58 ± 0.22 mg/L), group D (1.23 ± 0.11 mg/L), group E (1.20 ± 0.15 mg/L), and group F (1.18 ± 0.13 mg/L). Cerebral
triphosphate diphosphohydrolase (NTPDase) using
adenosine triphosphate (
ATP) as a substrate and
5'-nucleotidase activities decreased in fish exposed to 72 h of
hypoxia compared with the normoxia group, while
adenosine deaminase (ADA) activity and levels of
nitric oxide (NOx) metabolites were higher. Dietary supplementation with 5% and 8%
caffeine prevented all alterations elicited by
hypoxia, with the exception of ADA activity in the case of 5%
caffeine. Based on this evidence, our findings reveal that
nucleotide/
nucleoside hydrolysis is modified in the brains of fish exposed to 72 h of
hypoxia, contributing to inflammatory damage, which apparently is mediated by excessive
ATP content in the extracellular medium and by excessive NOx production. Also, the use of a diet containing 5% and 8%
caffeine prevented these alterations (except 5% of dietary
caffeine on ADA activity) and can be considered an interesting approach to preventing the impairment of immune and inflammatory responses elicited by
hypoxia, principally the inclusion of 8%
caffeine.