Tissue Damage, Mutagenic Effect, and Alteration in Antioxidant Defense in Danio rerio (Cypriniformes: Cyprinidae) after Chronic Exposure to Metformin Hydrochloride.

Basic sanitation systems are not fully effective in removing all the contaminants, promoting contamination to rivers and supply reservoirs. The Metformin hydrochloride (MTF) is one of the most pharmaceutical contaminant found in rivers. The aim of this study was to test the potential effects of MTF sublethal concentrations on the antioxidant system, and mutagenic and tissue damages in Danio rerio. The animals were acclimatized and separated into six groups and exposed to different concentrations of MTF (0, 250, 500, 750, 1250 mg L-1) over 96 hours to determine the Lethal Concentration of 50% of the population (LC50). In another experiment, five groups of ten animals were separated: four groups for evaluation of the chronic effect of 450 g L-1 of MTF (15, 30, 45 and 60 days) and a negative control group (NC). The antioxidant system (SOD, CAT, GST, LPO) and the tissue damage (AST, ALT, CK, CK-MB) were analyzed in the muscle samples, and the mutagenicity assessment (MN and nucleus abnormalities) were performed in the blood samples. Univariate statistical analyzes were performed, as well as integrative analyzes of the Antioxidant System, Tissue Damage and Mutagenicity domains were performed using Principal Component Analysis. The results showed evidence of oxidative stress with changes in lipid peroxidation, mutagenicity with a significant increase in the frequency of micronucleus, and activation of the antioxidant system up to 30 days of treatment. There were also intense tissue damage and the emergence of apoptotic cells at 60 days. This evidence of the toxic effects promoted by sublethal concentrations of MTF can lead to irreversible metabolic damage which reduces the ability of nontarget animals to survive.