PUBLICATION
Structure-toxicity relationship of cefoperazone and its impurities to developing zebrafish by transcriptome and Raman analysis
- Authors
- Han, Y., Qian, J., Zhang, J., Hu, C., Wang, C.
- ID
- ZDB-PUB-170504-10
- Date
- 2017
- Source
- Toxicology and applied pharmacology 327: 39-51 (Journal)
- Registered Authors
- Zhang, Jing-pu
- Keywords
- Cefoperazone, Differentially expressed genes, Impurities, Raman mapping, Transcriptomics, Zebrafish embryos
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/chemistry
- Anti-Bacterial Agents/toxicity*
- Cefoperazone/chemistry
- Cefoperazone/toxicity*
- Embryo, Nonmammalian/pathology
- Embryonic Development/drug effects
- Embryonic Development/genetics
- Gene Expression/drug effects
- Gene Expression Profiling
- Gene Regulatory Networks/drug effects
- Microarray Analysis
- Signal Transduction
- Spectrum Analysis, Raman
- Structure-Activity Relationship
- Transcriptome/drug effects*
- Zebrafish
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/genetics
- PubMed
- 28465218 Full text @ Tox. App. Pharmacol.
- CTD
- 28465218
Citation
Han, Y., Qian, J., Zhang, J., Hu, C., Wang, C. (2017) Structure-toxicity relationship of cefoperazone and its impurities to developing zebrafish by transcriptome and Raman analysis. Toxicology and applied pharmacology. 327:39-51.
Abstract
Cefoperazone (CFP) is a potent antibacterial agent that is widely used for the treatment of bacterial infections. Previously, we found that both the C-7 and C-3 substituents of CFP are toxic functional groups, and two groups could affect gene expression in zebrafish embryos, thereby resulting in variable abnormal phenotypes. (6R, 7S)-cefoperazone (7S-CFP) is the 7-epimer of CFP and 1-methyl-1H-tetrazole-5-thiol (MTT) is the C-3 substituent of CFP. Both molecules are impurities isolated from CFP that can induce adverse effects. Transcriptome analysis was performed in the present study to identify differentially expressed genes (DEGs), coupled with Raman mapping of individual organ regions to detect changes in the biochemical composition of zebrafish embryos, which reflect the differences in distribution of the compounds. CFP, 7S-CFP, and MTT exposure altered the expression of 254, 368, and 1153 genes, respectively. Gene ontology analysis revealed that various processes related to development, growth, and morphology of tissues were significantly enriched with DEGs. We integrated seven co-DEGs with protein-protein interaction networks and identified various developmental processes that were regulated by the three compounds, including vasodilation, eye, brain, melanogenesis, and heart looping. Our findings suggested that Calca and Ptger4a may be potentially utilized as novel biomarkers for CFP, which causes bleeding. Raman analysis indicated that CFP, 7S-CFP, and MTT exhibited abnormal maps in tissues, which coincided with changes in their expression and morphological features. This study may provide bioinformatics and spectral information that may be used in further investigations on the relationship between structure and toxicity of drugs and impurities.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping