Efeitos tóxicos da finasterida e testosterona livres e complexadas a ciclodextrina na fisiologia e comportamento de Danio rerio

Abstract

Finasteride and testosterone are hormones that have anti-androgenic action (inhibition of 5α-reductase) and androgen respectively, which can act as endocrine disruptors causing negative effects on aquatic animals and their offspring. Finasteride was initially developed to treat benign prostatic hyperplasia, however, was presented as a major discovery in the treatment of androgenetic alopecia (baldness) already the testosterone is the hormone responsible for secondary sexual characteristics and has the most active metabolite the dihydrotestosterone, main responsible for baldness. However, finasteride as well as testosterone are commonly used in various situations, both by men in the treatment against hair loss (finasteride) or sexual reversal of fish (testosterone), which increases the presence of these hormones in the aquatic environment. Once in the environment both finasteride and testosterone begin to have action of endocrine disruptors, being one of the most powerful aquatic pollutants. Because it has hydrophobic properties which reduces their bioavailability, such hormones can be complexed to cyclodextrins (CDs) to reduce this limitation, therefore its use in inclusion complexes would increase its solubility and absorption, and may change one or more hormonal pathways. In view of the foregoing, the present study aims to evaluate the toxic effects of the inclusion complex Finasteride β-cyclodextrin (β-CD) and Testosterone β-cyclodextrin (β-CD), through chronic exposure to sublethal concentrations under the embryos and adults of the zebrafish (Danio rerio). The work was aimed to evaluate the toxic effects of finasteride and testosterone free and complexed into cyclodextrin on the physiological and behavioral parameters of embryos and adults of the Danio rerio fish. The embryos were exposed for periods of 96 hours post-fertilization for the evaluation of mortality, teratogenic effects, and heart rate. The groups were divided into control, free finasteride (FIN) and testosterone (T) at the concentrations of 280, 560, 1120, 2240, 4480 ng/L, and finasteride (FIN-β-CD) and testosterone (T-β-CD) complexed into β-CD at concentrations of 280 and 4480 ng/L. Adults were exposed for a period of 60 days to evaluate behavioral changes and daily survival related to exposure to free finasteride (FIN) and testosterone (T) complexed into β-CD at concentrations 280 and 4480 ng/L. The embryos did not exhibit mortality at concentrations of 280 - 4480 ng/L in the all groups exposed. Similarly, it was not observed teratogenic effects in the groups exposed to different concentrations. In the heart frequencies of the embryos, significant variations were observed (p < 0 .05) when compared to the control group. Adults exposed to free andcomplexed finasteride and testosterone had significant alterations (p < 0.05) in the most active behaviors such as slow swim and fast swim, as well as in agonistic behaviors. It can be concluded that in tests with embryos, FIN and FIN-β-CD as well T and T- β-CD, may interfere in the heart rate and the exposure of adults to the same hormones promoted a reduction in their locomotor capacity and can increase in the aggressiveness of the animals.