Calcium Chloride Toxicology for Food Safety Assessment Using Zebrafish (Danio rerio) Embryos.

The salt calcium chloride (CaCl2) is widely used in industry as a food additive; levels for human consumption are regulated by international or governmental agencies. Generally, the food industry relies on toxicity studies conducted in mammals such as mice, rats, and rabbits for determining food safety. However, testing in mammals is time-consuming and expensive. Zebrafish have been used in a range of toxicological analyses and offer advantages with regard to sensitivity, time, and cost. However, information in not available with regard to whether the sensitivity of zebrafish to CaCl2 is comparable to the concentrations of CaCl2 used as food additives. The aim of this study was to compare the CaCl2 tolerance of zebrafish embryos and larvae with concentrations currently approved as food additives. Acute toxicity, embryotoxicity, cardiotoxicity, and neurotoxicity assays were used to determine the threshold toxic concentration of CaCl2 in zebrafish embryos and larvae. The data showed that doses above 0.4% had toxic effects on development and on the activity of the cardiac and neuronal systems. Furthermore, all embryos exposed to 0.8 and 1.6% of CaCl2 died after 24 hpf. These findings are consistent with the limits of CaCl2 concentrations approved by Codex Alimentarius. Therefore, zebrafish embryos could be suitable for screening food additives.

The endocannabinoid system in zebrafish and its potential to study the effects of Cannabis in humans.

Zebrafish is considered an unprecedented animal model in drug discovery. A review of the literature presents highlights and elucidates the biological effects of chemical components found in Cannabis sativa. Particular attention is paid to endocannabinoid system (eCB) and its main receptors (CB1 and CB2). The zebrafish model is a promising one for the study of cannabinoids because of the many similarities to the human system. Despite the recent advances on the eCB system, there is still the need to elucidate some of the interactions and, thus, the zebrafish model can be used for that purpose as it respects the 3Rs concept and reduced time and costs. In view of the relevance of cannabinoids in the treatment and prevention of diseases, as well as the importance of the zebrafish animal model in elucidating the biological effects of new drugs, the aim of this study was to bring to light information on the use of the zebrafish animal model in testing C. sativa-based medicines.

Zebrafish toxicological screening could aid Leishmaniosis drug discovery.

BACKGROUND: Recently a screen from a library of 1.8 million compounds identified in vitro a potent activity of the 2-aminobenzimidazoles series against Leishmania infantum, the etiological agent responsible by over 20.000 deaths each year. Several analogs were synthesized and in vitro tested through an optimization program, leading to a promising 2-aminobenzimidazoles derived compound (2amnbzl-d) that was progressed to in vivo mice studies. However, the not expected toxic effects prevented its progression to more advanced preclinical and clinical phases of drug development. Due to limitations of cell models in detecting whole organism complex interactions, 90% of the compounds submitted to pre-clinical tests are reproved. The use of Zebrafish embryo models could improve this rate, saving mammals, time and costs in the development of new drugs. To test this hypothesis, we compared 2amnbzl-d with two compounds with already established safety profile: carbamazepine and benznidazole, using an embryo Zebrafish platform based on acute toxicity, hepatotoxicity, neurotoxicity and cardiotoxicity assays (Pltf-AcHpNrCd). RESULTS: Tests were performed blindly, and the results demonstrated the presence of lethal and teratogenic effects (CL50%: 14.8 µM; EC50%: 8.6 µM), hepatotoxic in concentrations above 7.5 µM and neurotoxic in embryos exposed to 15 µM of 2amnbzl-d. Nevertheless, benznidazole exposition showed no toxicity and only the 100 µM of carbamazepine induced a bradycardia. CONCLUSIONS: Results using Pltf-AcHpNrCd with zebrafish reproduced that found in the toxicological tests with mammals to a portion of the costs and time of experimentation.

Zebrafish as an alternative animal model in human and animal vaccination research.

Much of medical research relies on animal models to deepen knowledge of the causes of animal and human diseases, as well as to enable the development of innovative therapies. Despite rodents being the most widely used research model worldwide, in recent decades, the use of the zebrafish (Danio rerio) model has exponentially been adopted among the scientific community. This is because such a small tropical freshwater teleost fish has crucial genetic, anatomical and physiological homology with mammals. Therefore, zebrafish constitutes an excellent experimental model for behavioral, genetic and toxicological studies which unravels the mechanism of various human diseases. Furthermore, it serves well to test new therapeutic agents, such as the safety of new vaccines. The aim of this review was to provide a systematic literature review on the most recent studies carried out on the topic. It presents numerous advantages of this type of animal model in tests of efficacy and safety of both animal and human vaccines, thus highlighting gains in time and cost reduction of research and analyzes.