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

Abstract

The antidiabetic drug metformin is widely prescribed and found in high concentrations in the environment around the world, raising concern about potential impacts on aquatic life. Fish have a fundamental ecological role and are considered excellent experimental models in ecotoxicology studies. Gills of sh are extremely sensitive to even minor chemical or physical changes in the surroundings, mainly because of the large surface of the respiratory epithelium and the high perfusion rate, which both facilitate the entry of pollutants into this tissue.This study aimed to evaluate the occurrence of morphological changes in the gills of Astyanax lacustris exposed to metformin. The animals were subjected to different concentrations of the drug (50 ug/L, 100 ug/L, 1 mg/L and 10 mg/L) for a period of 90 days. Histopathological analyses were performed using light and Scanning Electron Microscopy. The main changes were lamellar fusion, telangiectasia hyperplasia and disappearance of microridges. The observed effects occurred at environmentally relevant concentrations, pointing to a concern that metformin may pose a risk to Astyanax lacustris and likely to other sh species.

Environmental concentrations of the antidiabetic Metformin cause liver damage in Astyanax lacustris (Lütken, 1875) individuals after chronic exposure

“…Adverse effects of the antidiabetic have been observed in some sh species, such as Pimephales promelas, Oryzias latipes, Betta splendens, and Astyanax lacustris. The observed changes include variations in vitellogenin levels, estrogen receptor levels, gonadotropin-releasing hormone levels, alterations in the expression of the CYP19A gene, presentation of oxidative stress, endocrine disruption, effects on animal behavior and morphological modi cations in gills (Crago et al, 2016;Lee et al, 2019; Maclaren; Wisniewski; Maclaren, 2018; Barbieri, 2022). Among the most notable effects of Metformin is the occurrence of intersex individuals in male P. promelas, induced by activation of vitellogenin mRNA transcription, a protein responsible for vitellogenesis that usually is only expressed in females (Niemuth et al, 2015).…”