Pharmaceuticals are emerging contaminants that are not regularly monitored and are constantly
being introduced into the aquatic ecosystem, and their impacts on non-target organisms are still
poorly understood. As a priority, metformin (MET) is one of the most widely used
hypoglycemic agents in the treatment of Type 2 Diabetes Mellitus, whose presence in aquatic
environments has been detected at concerning concentrations worldwide, causing undesirable
effects on aquatic biota and the local ecosystem. The aim of this study was to evaluate the
potentially toxic effects of acute exposure to MET on the Amazonian teleost Colossoma
macropomum, with emphasis on alterations in energy metabolism. The fish were randomly
divided into four groups (n=10) control and exposed to different environmental concentrations
of MET (10 μg L -1 , 80 μg L -1 , and 400 μg L -1 ) for 48 hours. Blood samples were collected for
hematological analysis and plasma separation. Liver and muscle samples were collected and
frozen for biochemical biomarker analysis of energy metabolism. Subsamples were fixed for
histopathological analysis. After the leukocyte differential analysis, a significant increase in
circulating monocytes was observed in the treated groups compared to the control group,
suggesting an immune system response to MET concentrations in a dose-dependent manner.
There were also adjustments in energy metabolism, evidenced by a reduction in hepatic
glycogen in the group exposed to 10 μg L -1 to maintain plasma glucose and a decrease in free
amino acids in plasma with a significant increase in white muscle, being the most pronounced
alterations. The increase in MET concentration indicates a concentration-dependent response,
suggesting that the exacerbated disposal of this drug into the environment may lead to
deleterious effects on fish when exposed to high concentrations and long exposures. In acute
exposure of 48 hours, no hepatotoxicity was observed in the analysis of hepatic morphology;
however, there is a metabolic recruitment for detoxification and animal survival.
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