Efeitos da cloroquina sobre biomarcadores de peixe-zebra (Danio rerio)

Abstract

Chloroquine is used to treat malaria and autoimmune diseases such as lupus and rheumatoid arthritis due to its anti-inflammatory and immunomodulatory properties, but its use increased significantly during the COVID-19 pandemic due to its recommendation as a prophylactic treatment. This increase in consumption, associated with inadequate disposal, resulted in the presence of the drug in wastewater and surface waters in several countries. In this context, this study aimed to compile environmental and ecotoxicological data on Chloroquine and Hydroxychloroquine in the aquatic environment and to reproduce in the laboratory a chronic toxicity test of Chloroquine Diphosphate (CQD), lasting 21 days, in a semi-static system, using the model species zebrafish (Danio rerio), exposed to environmentally relevant concentrations detected before the pandemic (0.6 µg/L) and during the pandemic (1.8; 5.4; 16.2 and 48.6 µg/L), to evaluate the changes caused by the drug. Biomarkers were analyzed in biochemical functions, including changes in the concentration of total proteins, glucose, triglycerides and immunoglobulins (Ig); enzymatic activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and glutathione S-transferase (GST); and oxidative stress measured by protein carbonyls (PCO) and thiobarbituric acid reactive substances (TBARs). Histological analyses evaluated gill, liver and kidney changes. Data were statistically compared between the control and exposed groups, using the nonparametric Kruskal-Wallis test with Dunn's post-test, through the PAST® software. The results showed metabolic, enzymatic and histopathological disturbances in the organs from the concentrations recorded in surface waters (0.6 µg/L and 1.8 µg/L). In addition, the concentration of 1.8 µg/L was the most responsive to biomarkers of oxidative stress. In the principal component analysis (PCA), the most responsive biomarkers to DCQ exposures were AST enzyme activity, TBARs in the brain, dilation of the central venous sinus in the gills, hepatocytes with pyknotic nuclei in the liver and reduction of Bowman's space in the kidney. The innovative aspect of this research lies in the understanding of the chronic toxicity of environmental concentrations of DCQ on biomarkers of D. rerio and underscores the importance of greater awareness about the responsible use and disposal of drugs, reinforcing the need for monitoring and remediation policies to protect water resources and aquatic life.