PUBLICATION
Thiacloprid-induced hepatotoxicity in zebrafish: Activation of the extrinsic and intrinsic apoptosis pathways regulated by p53 signaling pathway
- Authors
- Xie, Z., Lu, G., Zhou, R., Ma, Y.
- ID
- ZDB-PUB-220330-11
- Date
- 2022
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 246: 106147 (Journal)
- Registered Authors
- Keywords
- Danio rerio, Hepatotoxicity, Neonicotinoid, ROS
- MeSH Terms
-
- Animals
- Apoptosis
- Chemical and Drug Induced Liver Injury*
- Neonicotinoids/toxicity
- Oxidative Stress
- Reactive Oxygen Species/metabolism
- Signal Transduction
- Thiazines
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism
- Water Pollutants, Chemical*/toxicity
- Zebrafish/metabolism
- PubMed
- 35349858 Full text @ Aquat. Toxicol.
Citation
Xie, Z., Lu, G., Zhou, R., Ma, Y. (2022) Thiacloprid-induced hepatotoxicity in zebrafish: Activation of the extrinsic and intrinsic apoptosis pathways regulated by p53 signaling pathway. Aquatic toxicology (Amsterdam, Netherlands). 246:106147.
Abstract
Thiacloprid (THCP) is one of the major neonicotinoid insecticides, and its wide use has led to high detection in various media of aquatic environment, posing potential risks to aquatic organisms. This study was focused on the phenotypic responses and mechanisms of toxicity in zebrafish (Danio rerio) upon treatment with waterborne THCP (0.4, 4 and 40 μM) for 21 days in vivo or 412.9 μM for 24 h in vitro. In vivo, we found that THCP induced severe oxidative stress, hepatic abnormalities, leakage of alanine aminotransferase and aspartate aminotransferase and apoptosis. The analysis of RNA-sequencing suggested the activation of the p53 signaling pathway under THCP exposure. The following in vitro study showed that THCP intoxication activated reactive oxygen species (ROS)-dependent p53 signaling pathway and induced hepatotoxicity in the zebrafish liver cells. The addition of p53 inhibitor pifithrin-α (10 μM) exerted protection against of THCP-induced hepatotoxicity by reducing oxidative stress and inhibiting the p53 signaling pathway and apoptosis. Moreover, gene expression analyses indicated that both the extrinsic and intrinsic apoptosis pathways were involved in apoptosis induced by p53 activation. Overall, our results suggest that activation of the p53 signaling pathway is an important mechanism of THCP-induced hepatotoxicity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping