PUBLICATION
Relationship between fluoroquinolone structure and neurotoxicity revealed by zebrafish neurobehavior
- Authors
- Xiao, C., Han, Y., Liu, Y., Zhang, J., Hu, C.Q.
- ID
- ZDB-PUB-180322-11
- Date
- 2018
- Source
- Chemical Research in Toxicology 31(4): 238-250 (Journal)
- Registered Authors
- Zhang, Jing-pu
- Keywords
- none
- MeSH Terms
-
- Animals
- Behavior, Animal/drug effects*
- Chromatography, Liquid
- Fluoroquinolones/analysis
- Fluoroquinolones/chemistry*
- Fluoroquinolones/toxicity*
- Locomotion/drug effects*
- Molecular Structure
- Neurotoxicity Syndromes/embryology
- Neurotoxicity Syndromes/pathology*
- Tandem Mass Spectrometry
- Zebrafish
- PubMed
- 29561132 Full text @ Chem. Res. Toxicol.
Citation
Xiao, C., Han, Y., Liu, Y., Zhang, J., Hu, C.Q. (2018) Relationship between fluoroquinolone structure and neurotoxicity revealed by zebrafish neurobehavior. Chemical Research in Toxicology. 31(4):238-250.
Abstract
Central nervous system side effects are one of the most frequently reported adverse reactions of fluoroquinolones (FQs). However, the mechanism is not fully understood. In this study, zebrafish ( Danio rerio) were used as a model system. We quantified neurobehavior by recording indicators with automated video-tracking and used liquid chromatography-tandem mass spectrometry to detect drug absorption in vivo. We studied embryotoxicity and effects on zebrafish locomotor activity of 17 typical FQs. In addition, we calculated the stable conformation of typical FQs in aqueous conditions. The relationships between structure, neurotoxicity, and embryotoxicity were analyzed. The results indicate: (1) The effects of FQs on zebrafish neurobehavior can be divided into four categories. Type I has no significant influence on locomotor activity. Type II suppresses locomotor activity. Type III inhibits at low concentration and stimulates at high concentration. Type IV stimulates and then suppresses (biphasic response). (2) Structural modifications of FQs can change toxicity properties in zebrafish. Cleavage of the C-7 piperazinyl structure decreases neurotoxicity but enhances embryotoxicity. The C-3 decarboxyl formation and 5-NH2 derivatives might enhance embryotoxicity and neurotoxicity. (3) There are two toxic functional groups. The piperazinyl structure at position C-7 (toxic functional group I) can cause primary reactions which may be by the inhibition of γ-aminobutyric acid receptors, and the nucleus containing a carboxyl group at position 3 (toxic functional group II) might cause a reaction secondary to the effect of toxic functional group I and reverse its effects.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping