PUBLICATION
Folic acid mitigates the developmental and neurotoxic effects of bisphenol A in zebrafish by inhibiting the oxidative stress/JNK signaling pathway
- Authors
- Li, R., Yang, W., Yan, X., Zhou, X., Song, X., Liu, C., Zhang, Y., Li, J.
- ID
- ZDB-PUB-241121-17
- Date
- 2024
- Source
- Ecotoxicology and environmental safety 288: 117363117363 (Journal)
- Registered Authors
- Keywords
- Bisphenol A, Developmental and neurotoxicity, Folic acid, JNK/MAPK, Oxidative stress, Zebrafish
- MeSH Terms
-
- Phenols*/toxicity
- MAP Kinase Signaling System*/drug effects
- Reactive Oxygen Species/metabolism
- Endocrine Disruptors/toxicity
- Animals
- Zebrafish*
- Embryo, Nonmammalian/drug effects
- Benzhydryl Compounds*/toxicity
- Water Pollutants, Chemical/toxicity
- Folic Acid*
- Oxidative Stress*/drug effects
- Antioxidants/pharmacology
- PubMed
- 39566264 Full text @ Ecotoxicol. Environ. Saf.
Citation
Li, R., Yang, W., Yan, X., Zhou, X., Song, X., Liu, C., Zhang, Y., Li, J. (2024) Folic acid mitigates the developmental and neurotoxic effects of bisphenol A in zebrafish by inhibiting the oxidative stress/JNK signaling pathway. Ecotoxicology and environmental safety. 288:117363117363.
Abstract
Bisphenol A (BPA) is a widespread environmental endocrine disruptor (EED) that can cause various environmental and health issues by inducing oxidative stress. The c-Jun N-terminal kinase (JNK) signaling pathway plays a crucial role in oxidative stress-mediated cellular damage. Although folic acid (FA) has demonstrated antioxidant properties, its potential protective effects against BPA-induced developmental and neurotoxicity, as well as the mechanisms involved in the JNK signaling pathway, are still not completely understood. Zebrafish embryos were exposed to different concentrations of BPA ranging from 20 to 40 µM, with or without treatment of 50 µM FA, starting at 6 hours post-fertilization (hpf). Various parameters such as hatchability, survival rate, body length, and heart rate were measured and analyzed. Transcriptome sequencing was conducted to study the changes in gene expression. Oxidative stress markers, including reactive oxygen species (ROS), lipid peroxidation (LPO), hydrogen peroxide (H2O2), and catalase (CAT) activity, were assessed. The expression of proteins related to the mitogen-activated protein kinase (MAPK)/JNK pathway was analyzed using western blot. Neurodevelopmental and apoptotic outcomes were evaluated through behavioral tests, immunofluorescence and RT-qPCR examinations. The study found that exposure to BPA led to a decrease in hatchability, survival, body length, heart rate, total antioxidant capacity and promoted apoptosis in zebrafish larvae. However, supplementation with FA was able to alleviate these negative effects. BPA exposure increased levels of ROS, LPO, and H2O2, while decreasing CAT activity in zebrafish larvae. Treatment with FA effectively reduced BPA-induced oxidative stress and restored antioxidant defense systems. Moreover, KEGG pathway enrichment analysis revealed that the MAPK signaling pathway was the most enriched signaling pathway. Further studies revealed that BPA activated the JNK signaling pathway, while FA suppressed this activation. Additionally, FA significantly improved BPA-induced neurobehavioral deficits and protected against neurocytological alterations. Our findings demonstrate that FA effectively protects against BPA-induced developmental and neurotoxic effects in zebrafish by suppressing oxidative stress and inhibiting the JNK signaling pathway. This study provides new strategies and insights for preventing BPA-induced developmental and neurotoxicity in aquatic organisms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping