Uso do peixe-zebra Danio rerio (Hamilton, 1822) como modelo alternativo para avaliação da toxicidade de novos compostos com ação antimicrobiana

Abstract

The discovery of antibiotics is considered one of the major scientific revolutions of mankind because it allowed a significant increase in life expectancy and made possible the existence of effective therapy for infections that until then were fatal. Social neglect in the use of antibiotics contributes directly to the emergence of a major problem in the area of public health, antimicrobial resistance. The scarcity of new antimicrobial agents to replace those already ineffective makes the development of new drugs urgently. The use of heterocyclic rings has shown advantages for the synthesis of pharmaceutical compounds with different pharmacological activities. Recent studies have revealed that indole and pyrazole derivatives have a broad spectrum of biological activities, and their antimicrobial potential is highlighted. Recently, zebrafish (Danio rerio), in its embryo-larval stage, has emerged as an efficient model for the characterization of the toxicological properties of new compounds. Its high degree of homology with mammals allows the extrapolation of the results to humans more directly than the other invertebrate models and in a more economical way in relation to rodents. The study aimed to use zebrafish embryos to evaluate the toxicity of two new heterocyclic synthetic compounds that present potential for the development of new antimicrobial agents derived from indole and pyrazole compounds. Embryos with 3 hours post-fertilization (hpf) were exposed by immersion at concentrations of 0 (Control), 1, 8 and 32 μg/mL of the compounds, diluted in DMSO (0.005%), statically for 7 days. Mortality and hatch rate were evaluated daily and, at the end of the exposure period, the larvae were submitted to the Novel Tank exploratory behavioral test. Embryos exposed to the compounds had a significant increase in mortality, when compared to the control group. This effect was concentration-dependent. Significant decreases in hatching rate were also evident at the highest concentrations tested. It was possible to observe changes in the exploratory behavior of the embryos at the end of the exposure, even at the lowest concentration tested (1 μg/mL), in relation to the control. Our results quickly and satisfactorily demonstrate the embryotoxic effects of different candidate drug compounds on the development of zebrafish. Thus, D. rerio is shown as a predictive correlative model for the study of new molecules with antimicrobial potential capable of presenting the complexity of a vertebrate animal with the advantages of an invertebrate.