LORRÂNNY PEREIRA DE ASSIS VALADARES

AUTHOR: LORRÂNNY PEREIRA DE ASSIS VALADARES

TITLE: NANOPARTICLES OF SILICA (SO2) AS DRUG DELIVERY OF DOMPERIDONA IN Danio rerio

ADVISOR: MÔNICA RODRIGUES FERREIRA MACHADO

DEFENSE DATE: 02/18/2020

ABSTRACT

Domperidone is a dopamine D2 receptor inhibitor that stimulates the release of pituitary gonadotropins. It is usually associated with synthetic GnRHa to promote spawning in fish. However, the route of administration used, intramuscular injection, can be quite stressful for the breeder. Little is known about the isolated effects of domperidone, nor whether, with other routes of administration, this drug would be able to promote spawning. Initially, Zebrafish embryo toxicity (ZET) was carried out according to OECD manuals. For that, the toxicity of silica nanoparticles (SiNPs), domperidone (DOMP) and their association (DOMP + SINPs) was evaluated, in different concentrations, during 168 hours of exposure. A higher survival rate was observed when testing the DOMP + SiNPs association when compared to the other treatments and controls. The DOMP and SiNPs treatments showed the highest number of teratogenic effects, in the highest concentrations. In the evaluation of heart rate, DOMP treatment 0.004 mg / mL, increased frequency, compared to control. The SiNPs 4.4 mg / mL treatment decreased the heart rate of the embryos, compared to the control. The DOMP + SiNPs treatment showed no difference in terms of teratogenic effects and heart rate compared to control. The results demonstrate that the use of SiNPs decreased the toxicity of domperidone, in addition to allowing administration by dilution. Subsequently, the effect of these treatments on follicular growth in prepubertal zebrafish was evaluated, using two routes of administration, dilution in water and feed, for 14 days. An increase in the gonadosomatic index was observed in fish fed with diets containing SiNPs. Regardless of the route of administration, treatment with DOMP showed greater follicular maturation. Evaluating the routes of administration, DOMP ration treatment increased follicular maturation. In the early stages of follicular maturation, the DOMP and DOMP + SINPs (water) treatments increased the follicular area. The results show that there was an increase in the quantity of vitellogenic follicles in the DOMP and DOMP + SiNPs treatments administered via feeding and dilution, which would allow their incorporation into the diet or addition to the breeding tanks to promote spawning.