PUBLICATION
Benzydamine rescues ethanol-induced teratogenesis in zebrafish FASD model
- Authors
- Dasgupta, T., Manickam, V., Tamizhselvi, R.
- ID
- ZDB-PUB-250318-13
- Date
- 2025
- Source
- Scientific Reports 15: 90669066 (Journal)
- Registered Authors
- Keywords
- Cellular damage, Ethanol, FASD, Glutathione, Malformations, Oxidative stress
- MeSH Terms
-
- Benzydamine*/metabolism
- Oxidative Stress*/drug effects
- Zebrafish*/embryology
- Female
- Reactive Oxygen Species/metabolism
- Ethanol*/adverse effects
- Ethanol*/toxicity
- Antioxidants/metabolism
- Antioxidants/pharmacology
- Disease Models, Animal*
- Teratogenesis*/drug effects
- Lipid Peroxidation/drug effects
- Fetal Alcohol Spectrum Disorders*/metabolism
- Fetal Alcohol Spectrum Disorders*/prevention & control
- Animals
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Glutathione/metabolism
- PubMed
- 40097574 Full text @ Sci. Rep.
Citation
Dasgupta, T., Manickam, V., Tamizhselvi, R. (2025) Benzydamine rescues ethanol-induced teratogenesis in zebrafish FASD model. Scientific Reports. 15:90669066.
Abstract
Fetal alcohol spectrum disorders (FASD) are a group of physical, behavioral, and cognitive impairments caused by ethanol exposure during pregnancy. Zebrafish have emerged as a useful model for researching FASD and its variants in recent years. Oxidative stress has been identified as the primary damaging pathway, notwithstanding the possibility of other mechanisms at play. In this regard it's important to put an effort towards antioxidants which can exhibits and bare a potential to counteract the oxidative stress induced by ethanol during embryos development. Previosuly benzydamine has shown to protect macrophages against ethanol-induced condition by stabilizing redox homeostatis. This study aims to repurpose the Non-Steroidal Anti-Inflammatory Drug (NSAID) benzydamine to mitigate ethanol-induced teratogenesis during the early embryonic stage in Zebrafish. Zebrafish embryos were treated with 1% ethanol at 2 h post fertilization (hpf) and co-exposed with benzydamine (5-20 µM) after 2 h of ethanol treatment for 24 h. Reactive oxygen Species (ROS) and biochemical analysis was carried out at 48hpf. 1% ethanol significantly increased the production of ROS along with increased in lipid peroxidation followed by a decrease in glutathione (GSH) level when compoared to the control group (P < 0.001). These conditions were positively encountered by benzydamine (10, 15 µM) and returned to basal level. Involvement of two ethanol metabolizing enzymes cyp2y3 (Cytochrome P450, family 2, subfamily Y, polypeptide 3) and cyp3a65 Cytochrome P450, family 3, subfamily A, polypeptide 65 ) were also studied at 48hpf. 1% ethanol exposure aggregately elevated the expression of these two enzymes which showed a significant decrease in the benzydamine treated groups. Furthermore, the malformations and cellular damage due to 1% ethanol was studied at 96hpf, where 1% ethanol made severe malformation along with muscle fiber alteration, apoptosis in the brain and eye as manifested. These conditions were successfully reverted by benzydamine. In conclusion, ethanol causes oxidative stress, cellular damage along with severe malformation at early embryonic stage, which were partially prevented by the exposure of benzydamine.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping