Estudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra.

Abstract

Clioquinol (CQ) belongs to the class of anti-infective and antimicrobial agents. In the 1970s, CQ was withdrawn from the market due to reports of neurotoxicity in patients in Japan, and being associated with the manifestation of a neurodegenerative syndrome (SMON). Despite the exclusion of the drug for oral treatments, topical formulations for treating fungal and parasitic infections remained available. CQ is currently available as a topical antibiotic under the tradename Vioformi®. Given the potential reintroduction of oral QC formulations for novel indications, a better understanding of its toxicity is needed. This study intends to enhance our knowledge about the potential toxicity caused by CQ evaluating its effects on the embryonic development of zebrafish (Danio rerio). The embryos were exposed the concentrations of 0.1, 0.5, 1.0, 1.5 and 2.0 μg/ml of the CQ for 168 hours, evaluating the physiological, morphological and behavioral parameters. It was found that CQ exhibits a wide spectrum of toxicity and causes 100% mortality in the first 48 hours at concentrations of 1.5 and 2.0 μg/ml therefore; these concentrations were excluded from further evaluations. We observed a delay in hatching rate evaluated after 72 hours of exposure to 1 μg/ml; in addition, at the concentrations of 0.5 and 1.0 μg/ml, four main types of morphological abnormalities were observed. The exploratory behavior of the larvae was also examined in 7 dpf (days after fertilization) to determine if the exposure to CQ could alter the locomotion and orientation of the larvae. The behavior was evaluated only at the lowest CQ concentration tested in which the morphological alterations were not severe. Exposure of larva to CQ 0.1 μg/ml resulted in altered swimming patterns and it is suggested that the observed locomotor alterations may be associated with damage caused by CQ. In summary, this study is the first to demonstrate the potential embryotoxicity induced by CQ in zebrafish.