TY - JOUR
T1 - Chronic exposure to realistic concentrations of metformin prompts a neurotoxic response in Danio rerio adults
AU - Elizalde-Velázquez, Gustavo Axel
AU - Gómez-Oliván, Leobardo Manuel
AU - García-Medina, Sandra
AU - Rosales-Pérez, Karina Elisa
AU - Orozco-Hernández, José Manuel
AU - Islas-Flores, Hariz
AU - Galar-Martínez, Marcela
AU - Hernández-Navarro, María Dolores
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/11/25
Y1 - 2022/11/25
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Behavior
KW - Emerging contaminant
KW - Neurotoxicity
KW - Oxidative damage
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=85135942011&partnerID=8YFLogxK
U2 - 10.1016/j.scitotenv.2022.157888
DO - 10.1016/j.scitotenv.2022.157888
M3 - Artículo
C2 - 35952892
AN - SCOPUS:85135942011
SN - 0048-9697
VL - 849
JO - Science of the Total Environment
JF - Science of the Total Environment
M1 - 157888
ER -