A indução do comportamento tipo ansiedade e estresse oxidativo pela indometacina no cérebro do Danio rerio (Zebrafish) é prevenida pelo alfa-tocoferol

Abstract

The non-steroidal anti-inflammatory drugs are among the most used and prescribed in the world, however this type of drug has several side effects at the neural level. Studies related to neurobehavioral and neurochemical damage of this class of drug are still necessary for a better understanding of all the possible damages that they can cause. As a result, indomethacin, which is an NSAID, has been widely used to treat pathologies such as rheumatoid arthritis, musculoskeletal injuries, osteoarthritis and postoperative pain. Indomethacin non-selectively blocks the enzymes COX-1 and COX-2, acting to decrease the production of prostaglandins. Therefore, this study proposed that the indomethacin could be generated anxiogenic effects and oxidative stress in the brain, and whether the antioxidant α-tocopherol exercised protection against the possible damage caused by indomethacin in zebrafish. The animals used were fish of the species Danio rerio (n=160), subdivided into the following groups: Control - Saline 0.9%; Indomethacin - INDO 0.5 mg/kg; INDO 0.75 mg/kg; INDO 1.0 mg/kg; INDO 2.0 mg/kg; INDO 3.0 mg/kg; α-Tocopherol - TF; TF + INDO 1 mg/kg; TF + INDO 2 mg/kg and were subjected novel tank diving test, the parameters time on top, freezing, erratic swimming and crossed quadrants were analyzed. The statistical analysis of the results was performed using one-way ANOVA with a post-test bonferroni or tukey for comparison between groups, with values with p <0.05 being considered significant. The results regarding the behavioral parameters and oxidative stress were expressed as mean ± standard error or standard deviation. The parameters that showed statistical differences were the time at the top and freezing, where the animals of the groups INDO 0.5 mg/kg, INDO 0.75 mg/kg, INDO 1 mg/kg and INDO 2 mg/kg explored for less the top of the apparatus compared to the CTRL group. In the freezing parameter the groups treated with indomethacin INDO 0.5 mg/kg, 0.75 mg/kg and 2 mg/kg did not show statistical differences with the CTRL group, however there was a difference between the CTRL and INDO groups 1 mg/kg. In the freezing parameter, the animals in the INDO 1 mg/kg group showed a longer time without movement compared to the CTRL group. In the other parameters, there were no significant differences between the groups treated with the control group. The analysis of lipid peroxidation, the INDO 1 mg/kg and INDO 2 mg/kg groups showed an increase in MDA production compared to the CTRL group, thus inferring that there was an increase in oxidative stress when animals were treated with indomethacin. The α-tocopherol exercised protection when animals were previously treated in both the TF + INDO 1 mg/kg group and the TF + INDO 2 mg/kg group compared to the INDO 1 mg/kg and INDO 2 mg/kg groups, respectively. Therefore, indomethacin is involved in inducing anxiety-like behavior and oxidative stress in zebrafish brains.