Tissue damage, mutagenic effect and alteration in antioxidant defense in Danio rerio (Cypriniformes: Cyprinidae) after chronic exposure to Metformin hydrochloride.

Abstract Metformin hydrochloride (MET) is an oral medication very prescribed for patients with diabetes, with a large part of its metabolites being eliminated in the urine. Basic sanitation systems are not fully effective in removing all the contaminants, promoting contamination to rivers and supply reservoirs. The objective of this study was to test the potential acute and chronic effects of MET on the antioxidant system, mutagenicity effects and tissue damages in the bioindicator D. rerio. The animals were acclimatized and separated into six groups and exposed to different concentrations of MET (0.00, 0.25, 0.50, 0.75, 1.25 g.L− 1) over a 96 hour period to determine the LC50. In another experiment, five groups of ten animals were separated as follows: four groups for evaluation of the chronic effect of 0.45 g.L− 1 of metformin hydrochloride (15, 30, 45 and 60 days) and, a negative control group (NC). The antioxidant system and the tissue damages of the muscle samples and, the mutagenicity in the blood samples were evaluated. The presence of oxidative stress and mutagenicity, together with the activation of the antioxidant system, can be visualized up to 30 days of treatment, with intense tissue damages in 60 days and the emergence of apoptotic cells, which is evidence of the toxic potential of this drug to non-target aquatic populations.