PUBLICATION
Chronic exposure to realistic concentrations of metformin prompts a neurotoxic response in Danio rerio adults
- Authors
- Elizalde-Velázquez, G.A., Gómez-Oliván, L.M., García-Medina, S., Rosales-Pérez, K.E., Orozco-Hernández, J.M., Islas-Flores, H., Galar-Martínez, M., Hernández-Navarro, M.D.
- ID
- ZDB-PUB-220812-3
- Date
- 2022
- Source
- The Science of the total environment 849: 157888 (Journal)
- Registered Authors
- Keywords
- Apoptosis, Behavior, Emerging contaminant, Neurotoxicity, Oxidative damage, Zebrafish
- MeSH Terms
-
- Amyloid Precursor Protein Secretases/metabolism
- Animals
- Aspartic Acid Endopeptidases/metabolism
- Behavior, Animal
- Caspase 3/metabolism
- Metformin*/toxicity
- NF-E2-Related Factor 2/metabolism
- Swimming
- Tumor Suppressor Protein p53/metabolism
- Water/metabolism
- Water Pollutants, Chemical*/metabolism
- Water Pollutants, Chemical*/toxicity
- Zebrafish/physiology
- bcl-2-Associated X Protein/metabolism
- PubMed
- 35952892 Full text @ Sci. Total Environ.
Citation
Elizalde-Velázquez, G.A., Gómez-Oliván, L.M., García-Medina, S., Rosales-Pérez, K.E., Orozco-Hernández, J.M., Islas-Flores, H., Galar-Martínez, M., Hernández-Navarro, M.D. (2022) Chronic exposure to realistic concentrations of metformin prompts a neurotoxic response in Danio rerio adults. The Science of the total environment. 849:157888.
Abstract
Metformin (MET) is among the most consumed drugs around the world, and thus, it is considered the uppermost drug in mass discharged into water settings. Nonetheless, data about the deleterious consequences of MET on water organisms are still scarce and require further investigation. Herein, we aimed to establish whether or not chronic exposure to MET (1, 20, and 40 μg/L) may alter the swimming behavior and induce neurotoxicity in Danio rerio adults. After 4 months of exposure, MET-exposed fish exhibited less swimming activity when compared to control fish. Moreover, compared with the control group, MET significantly inhibited the activity of AChE and induced oxidative damage in the brain of fish. Concerning gene expression, MET significantly upregulated the expression of Nrf1, Nrf2, BAX, p53, BACE1, APP, PSEN1, and downregulated CASP3 and CASP9. Although MET did not overexpress the CASP3 gene, we saw a meaningful rise in the activity of this enzyme in the blood of fish exposed to MET compared to the control group, which we then confirmed by a high number of apoptotic cells in the TUNEL assay. Our findings demonstrate that chronic exposure to MET may impair fish swimming behavior, making them more vulnerable to predators.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping