PUBLICATION

Microcystin-LR exposure induced nephrotoxicity by triggering apoptosis in female zebrafish

Authors
Wang, Z., Li, G., Wu, Q., Liu, C., Shen, J., Yan, W.
ID
ZDB-PUB-181006-12
Date
2018
Source
Chemosphere   214: 598-605 (Journal)
Registered Authors
Keywords
Apoptosis, Microcystin-LR, Nephrotoxicity, Transcriptome, Zebrafish
MeSH Terms
  • Animals
  • Apoptosis/drug effects*
  • Enzyme Inhibitors/toxicity
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation/drug effects*
  • Kidney Diseases/chemically induced*
  • Kidney Diseases/genetics
  • Kidney Diseases/metabolism
  • Microcystins/toxicity*
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
PubMed
30290360 Full text @ Chemosphere
Abstract
Recently, several studies showed that microcystin-LR (MCLR) can accumulate and induce toxicity in kidney. However, the exact mechanism is unknown. The aim of this study was to explore the mechanism of MCLR-induced nephrotoxicity. To this end, adult zebrafish were exposed to MCLR (0, 1, 5 and 25 μg/L) for 60 days. Exposure to MCLR caused histopathological lesions, which were characterized by renal tubules filled with eosinophilic casts, abnormal renal tubules, intertubular space decrease, and blood infiltration in renal cells. RNA-Seq analysis indicated that exposure to MCLR significantly interfered with renal gene expressions, and these genes were enriched in various pathways, such as oxidative phosphorylation, cell cycle, and protein processing in endoplasmic reticulum, which were related to apoptosis. Furthermore, terminal deoxynucleotide transferase-mediated deoxy-UTP nick end labelling (TUNEL) assay showed that MCLR exposure induced renal cell apoptosis. In addition, negative changes of the reactive oxygen species (ROS) level as well as apoptotic-related gene, protein expressions and enzyme activities suggested that MCLR could induce production of ROS, subsequently triggering apoptosis via p53-bcl-2 and caspase-dependent pathway in the kidney of zebrafish. Therefore, it can be concluded that apoptosis is a primary case of MCLR-induced nephrotoxicity.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping