Effect of adenosine treatment on ionizing radiation toxicity in zebrafish early life stages.

The danger of ionizing radiation exposure to human health is a concern. Since its wide use in medicine and industry, the development of radioprotectors has been very significant. Adenosine exerts anti-inflammatory actions and promotes tissue protection and repair, by activating the P1 receptors (A1, A2A, A2B, and A3). Zebrafish (Danio rerio) is an appropriate tool in the fields of toxicology and pharmacology, including the evaluation of radiobiological outcomes and in the search for radioprotector agents. This study aims to evaluate the effect of adenosine in the toxicity induced by radiation in zebrafish. Embryos were treated with 1, 10, or 100 µM adenosine, 30 min before the exposure to 15 Gy of gamma radiation. Adenosine potentiated the effects of radiation in heart rate, body length, and pericardial edema. We evaluated oxidative stress, tissue remodeling and inflammatory. It was seen that 100 µM adenosine reversed the inflammation induced by radiation, and that A2A2 and A2B receptors are involved in these anti-inflammatory effects. Our results indicate that P1R activation could be a promising pharmacological strategy for radioprotection.

Effects of lipoic acid supplementation on age- and iron-induced memory impairment, mitochondrial DNA damage and antioxidant responses.

PURPOSE: To investigate the effects of lipoic acid (LA) supplementation during adulthood combined with supplementation later in life or LA administration only at old age on age-induced cognitive dysfunction, mitochondrial DNA deletions, caspase 3 and antioxidant response enzymes expression in iron-treated rats. METHODS: Male rats were submitted to iron treatment (30 mg/kg body wt of Carbonyl iron) from 12 to 14th post-natal days. Iron-treated rats received LA supplementation (50 mg/kg, daily) in adulthood and old age or at old age only for 21 days. Memory, mitochondrial DNA (mtDNA) complex I deletions, caspase 3 mRNA expression and antioxidant response enzymes mRNA expression were analyzed in the hippocampus. RESULTS: LA administration in adulthood combined with treatment later in life was able to reverse age-induced effects on object recognition and inhibitory avoidance memory, as well as on mtDNA deletions, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression, and antioxidant enzymes disruption induced by iron in aged rats. LA treatment only at old age reversed iron-induced effects to a lesser extent when compared to the combined treatment. CONCLUSION: The present findings support the view that LA supplementation may be considered as an adjuvant against mitochondrial damage and cognitive decline related to aging and neurodegenerative disorders.

Characterization of the adenosinergic system in a zebrafish embryo radiotherapy model.

Adenosine is a nucleoside that acts as a signaling molecule by activating P1 purinergic receptors (A1, A2A, A2B and A3). This activation is involved in immune responses, inflammation, and tissue remodeling and tumor progression. Gamma rays are a type of ionizing radiation widely adopted in radiotherapy of tumors. Although it brings benefits to the success of the therapeutic scheme, it can trigger cellular damages, inducing a perpetual inflammatory response that culminates in adverse effects and severe toxicity. Our study aims to characterize the adenosinergic system in a zebrafish embryo radiotherapy model, relating the adenosine signaling to the changes elicited by radiation exposure. To standardize the radiotherapy procedure, we established a toxicological profile after exposure. Zebrafish were irradiated with different doses of gamma rays (2, 5, 10, 15 and 20 Gy) at 24 hpf. Survival, hatching rate, heartbeats, locomotor activity and morphological changes were determined during embryos development. Although without significant difference in survival, gamma-irradiated embryos had their heartbeats increased and presented decreased hatching time, changes in locomotor activity and important morphological alterations. The exposure to 10 Gy disrupted the ecto-5'-nucleotidase/CD73 and adenosine deaminase/ADA enzymatic activity, impairing adenosine metabolism. We also demonstrated that radiation decreased A2B receptor gene expression, suggesting the involvement of extracellular adenosine in the changes prompted by radiotherapy. Our results indicate that the components of the adenosinergic system may be potential targets to improve radiotherapy and manage the tissue damage and toxicity of ionizing radiation.