TY - JOUR
T1 - Antidiabetic drug metformin disrupts the embryogenesis in zebrafish through an oxidative stress mechanism
AU - Elizalde-Velázquez, Gustavo Axel
AU - Gómez-Oliván, Leobardo Manuel
AU - García-Medina, Sandra
AU - Islas-Flores, Hariz
AU - Hernández-Navarro, María Dolores
AU - Galar-Martínez, Marcela
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/12
Y1 - 2021/12
N2 - In recent years, the consumption of metformin has increased not only due to the higher prevalence of type 2 diabetes, but also due to their usage for other indications such as cancer and polycystic ovary syndrome. Consequently, metformin is currently among the highest drug by weight released into the aquatic environments. Since the toxic effects of this drug on aquatic species has been scarcely explored, the aim of this work was to investigate the influence of metformin on the development and redox balance of zebrafish (Danio rerio) embryos. For this purpose, zebrafish embryos (4 hpf) were exposed to 1, 10, 20, 30, 40, 50, 75 and 100 μg/L metformin until 96 hpf. Metformin significantly accelerated the hatching process in all exposure groups. Moreover, this drug induced several morphological alterations on the embryos, affecting their integrity and consequently leading to their death. The most frequent malformations found on the embryos included malformation of tail, scoliosis, pericardial edema and yolk deformation. Regarding oxidative balance, metformin significantly induced the activity of antioxidant enzymes and the levels of oxidative damage biomarkers. However, our IBR analisis demonstrated that oxidative damage biomarkers got more influence over the embryos. Together these results demonstrated that metformin may affect the embryonic development of zebrafish and that oxidative stress may be involved in the generation of this embryotoxic process.
AB - In recent years, the consumption of metformin has increased not only due to the higher prevalence of type 2 diabetes, but also due to their usage for other indications such as cancer and polycystic ovary syndrome. Consequently, metformin is currently among the highest drug by weight released into the aquatic environments. Since the toxic effects of this drug on aquatic species has been scarcely explored, the aim of this work was to investigate the influence of metformin on the development and redox balance of zebrafish (Danio rerio) embryos. For this purpose, zebrafish embryos (4 hpf) were exposed to 1, 10, 20, 30, 40, 50, 75 and 100 μg/L metformin until 96 hpf. Metformin significantly accelerated the hatching process in all exposure groups. Moreover, this drug induced several morphological alterations on the embryos, affecting their integrity and consequently leading to their death. The most frequent malformations found on the embryos included malformation of tail, scoliosis, pericardial edema and yolk deformation. Regarding oxidative balance, metformin significantly induced the activity of antioxidant enzymes and the levels of oxidative damage biomarkers. However, our IBR analisis demonstrated that oxidative damage biomarkers got more influence over the embryos. Together these results demonstrated that metformin may affect the embryonic development of zebrafish and that oxidative stress may be involved in the generation of this embryotoxic process.
KW - Antidiabetic drug
KW - Embryotoxicity
KW - Metformin
KW - Oxidative stress
KW - Teratogenesis
UR - http://www.scopus.com/inward/record.url?scp=85109433200&partnerID=8YFLogxK
U2 - 10.1016/j.chemosphere.2021.131213
DO - 10.1016/j.chemosphere.2021.131213
M3 - Artículo
C2 - 34246938
AN - SCOPUS:85109433200
SN - 0045-6535
VL - 285
JO - Chemosphere
JF - Chemosphere
M1 - 131213
ER -