EVALUATION OF THE COCKTAIL EFFECT OF DIPYRONE, PARACETAMOL AND NIMESULIDE ON THE INITIAL DEVELOPMENT OF ZEBRAFISH (Danio rerio)
Acetaminophen, Combination, Embryotoxic assay, Metamizole, Emerging pollutants, Xenobiotics.
Pharmaceutical products, especially medicines, are of great importance to society. Growing consumption and inappropriate disposal are inserting these products into a new class of xenobiotics distributed as emerging pollutants, becoming a major public health concern. Fish, in particular the embryonic development of zebrafish, have been widely used in environmental toxicology research. Most works using fish have been focused mainly on the toxicological evaluation of isolated drugs, however, the effects of the mixture (cocktail) of these xenobiotics have been little explored and this is the possible scenario found in the environment. A previous study indicated that the most incorrectly discarded drugs by users of drugstores in the city of Divinópolis, MG were dipyrone, paracetamol and nimesulide. In this sense, our objective was to evaluate the cocktail effect of dipyrone, paracetamol and nimesulide during the embryonic development of zebrafish. The lethal concentration of 50% of the embryos at 96 h (CL 50-96 h) for the drugs of interest was determined. After this step, the following experimental groups were associated with the mixture: Control (E3 medium), CL 50/2, CL 50/5, CL 50/10 and CL 50/20. Embryos with 6-8 hours post fertilization (hpf) were submitted to the treatment and the following times were evaluated: 24, 48, 72 and 96 h. In the morphometric evaluation of the embryos, the number of heart beats, hatching rate and embryo mortality by development time, as well as the total length, size of the heart area and yolk sac edema were obtained. In addition, teratogenic effects have been verified. The LC 50/96 h calculated for dipyrone, paracetamol and nimesulide were, respectively, 4.69 mg/ml, 799.98 μg/ml and 0.92 μg/ml. After the toxicological tests, it was possible to observe that the exposure of the embryos to the mixture induced a significant increase in the mortality rate and a decrease in the hatching rate, being more frequent in the CL 50/5 and CL 50/2 concentrations, in addition, teratogenic effects were observed in the embryos, such as malformation of the head, curvature of the tail and spine, vitelline and pericardial edema and loss of pigmentation, with the most intense depigmentation in the eyeballs and dorsal region of the larvae, mainly in CL 50/5 and CL 50/2 concentrations . Finally, we believe that the present work, based on the results obtained, will make it possible to understand and extrapolate to nature the damage caused to living beings due to the accidental exposure of these xenobiotics released into the environment.