Effects of the acute and chronic exposures to simvastatin and clofibric acid in Danio rerio

• Autor(a) principal: Rebelo, Daniela Fonseca Costa
• Data de Publicação: 2019
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/29247
• topic: Fish; Antihyperlipidemic; Reproductive disruptors; Biomarkers; Histology; Zebrafish

Lipid-regulating drugs are one of the most prescribed medications around the world, to control human cholesterol levels, to more than 20 million patients. Due to their wide usage, pharmaceuticals can be discarded, metabolized and excreted into the environment, potentially affecting aquatic organisms. Despite this increasing use of lipid-regulating drugs, particularly simvastatin and clofibric acid, are not fully characterized and understood in terms of their potential toxicological effects at the environmental level, therefore being necessary to investigate them. Therefore, it emerges a new concern on their effects related to the potential environmental impact, particularly in the aquatic environment. This work intended to characterize the toxicity due to an acute (120 hours post-fertilization) and chronical (60 days) exposure to antihyperlipidemic drugs, namely simvastatin (92.45, 184.9, 369.8, 739.6 and 1479.2 ng L-1) and clofibric acid (10.35, 20.7, 41.4, 82.8 and 165.6 μg L-1), in the freshwater species of zebrafish (Danio rerio). The concentrations hereby selected were implemented in both exposures. The analysis of effects focused on the histological observation of tissues in individuals, concerning sex determination and maturation stages of gonads, behavior (small and large distance, total distance and swimming time), biomarkers of oxidative stress (superoxide dismutase, catalase and glutathione peroxidase), biotransformation (glutathione S-transferases) and lipid peroxidation (thiobarbituric acid reactive substances). In terms of acute exposure, it was observed behavioral alterations in both compounds, simvastatin caused hyperactivity and clofibric acid provoked hypoactivity in all behavioral parameters. Moreover, it was observed a significant decrease in all biomarkers in individuals exposed to simvastatin from 184.9 to 1479.2 ng L-1, except for catalase, for which no significant differences were found. Glutathione peroxidase selenium-dependent activity also showed a significant increase at 92.45 ng L-1. On the other hand, in individuals exposed to clofibric acid, there was a significant increase in all biomarkers, typically from 41.4 to 165.6 μg L-1. However, in catalase and glutathione S-transferases, in the highest concentration, the activity was significantly decreased. This study suggests that the chronic exposure of Danio rerio to simvastatin and clofibric acid does not interfere with the sex ratio and maturation stages of individuals. As antioxidant defenses are important in terms of the capacity of the organism to overcome oxidative stress, along with effects in locomotion, it can affect the metabolism or even the survival of organisms. Therefore, further studies in terms of mode of action of these two compounds, including reproductive disruption effects in longer exposures, are required to observe and characterize the long-term effects of simvastatin and clofibric acid in the aquatic compartment and its organisms.