Erythrocyte alterations in specimens of Danio rerio caused by exposure to metformin.

The antidiabetic drug metformin is widely prescribed around the world. However, its permanence in different environmental concentrations has been associated with adverse toxicological effects in organisms that do not target its therapeutic action. In the aquatic environment, fish such as the Zebrafish (Danio rerio) have been considered potential bioindicators of environmental impacts and used as experimental models in toxicological studies due to the sensitivity of these species to different types of contaminants, including pharmaceuticals. Thus, this study aimed to analyze metformin's cytotoxic effects on Danio rerio erythrocytes. The animals were submitted to different concentrations of the drug (50 µg/L, 100 µg/L, 150 µg/L, and 10000 µg/L) for 365 days and subsequently observed employing light microscopy and scanning electron microscopy (SEM) to evaluate the alterations that occurred. Exposure of animals to metformin led to significant erythrocyte cell abnormalities across all tested concentrations, with a particularly pronounced effect at the higher concentration previously defined as the NOEC (No Observed Effect Concentration). Remarkable abnormalities included cytoplasmic vacuoles, echinocytes, and vesicle-like cytoplasmic fragments. These findings suggest that metformin, even at concentrations similar to those found in nature and at the NOEC level, exhibits cytotoxic potential in D. rerio, raising concerns about its potential health impacts.

Metformin-induced alterations in gills of the freshwater fish Astyanax lacustris (Lütken, 1875) detected by histological and scanning electron microscopy.

The antidiabetic drug metformin is widely prescribed and found in different concentrations in the environment around the world, raising concern about potential impacts on aquatic life. Analyses of the effects of exposure of biological models to aquatic contaminants are important for assessing pollution effects on fish health. The gills of fishes represent primary targets of disturbance by pollutants, mainly because of the large surface of the respiratory epithelium and the high perfusion rate, which both help the entry of pollutants into this tissue. In this context, the aim of this work was to use gill histological analyses biomarkers to evaluate the toxicity of metformin on aquatic environmental systems, by means of chronic exposure for 90 days of Astyanax lacustris (lambari), an ecologically important neotropical species that can be used as an environmental bioindicator. Histopathological analyses were performed using Light and Scanning Electron Microscopy. The main changes were lamellar fusion, telangiectasia hyperplasia and disappearance of microridges. The morphological changes observed possibly interfere with the gill physiology, indicating an unfavorable situation to the presence of metformin in the water, pointing to a concern that metformin may pose a risk to Astyanax lacustris and likely to other fish species, compromising the dynamics of the aquatic ecosystem as a whole. Graphical abstract.

Metformin environmental exposure: A systematic review.

This review discussed the occurrence, ecological impacts, and effects of metformin, a drug used for type 2 diabetes among other diseases. It is one of the most commonly found medicines in aquatic environments owing to its incomplete metabolism in the human body, and is eventually disposed in wastewater. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed as a guide. After searching various databases, 48 eligible studies were selected for the review. Metformin reportedly occurs in different environmental matrices, as measurable concentrations of metformin are found in sewage (urban and hospital), influent/sludge/effluent from wastewater treatment plants, surface water (rivers, lakes, estuaries, oceans, and non-specific sources), tap/drinking water, and sediment (lake and recipient seawaters). Data on metformin detection in aquatic environments in 14 countries were studied, but a consensus on the risk patterns of pharmaceutical products was not determined. Many studies have been conducted on different test organisms, demonstrating that metformin can drive the expression of diverse genes, particularly those responsible for endocrine hormone pathways. Chronic exposure to metformin can be tested using models and other tools to understand this field, which remains largely unexplored. Our results contribute to the current ecotoxicology knowledge related to typically used drugs and provide a basis for further investigations.