Induction of time-dependent oxidative stress and related transcriptional effects of perfluorododecanoic acid in zebrafish liver

Liu, Y., Wang, J., Wei, Y., Zhang, H., Xu, M., and Dai, J.
Aquatic toxicology (Amsterdam, Netherlands)   89(4): 242-250 (Journal)
Registered Authors
PFDoA, Female zebrafish, Hepatotoxicity, Oxidative stress, Fatty acid β-oxidation, Real-time PCR
MeSH Terms
  • Acyl-CoA Dehydrogenase/genetics
  • Acyl-CoA Dehydrogenase/metabolism
  • Animals
  • Carnitine O-Palmitoyltransferase/genetics
  • Carnitine O-Palmitoyltransferase/metabolism
  • Catalase/metabolism
  • Electron Transport Complex IV/genetics
  • Electron Transport Complex IV/metabolism
  • Fatty Acid-Binding Proteins/genetics
  • Fatty Acid-Binding Proteins/metabolism
  • Female
  • Glutathione/metabolism
  • Glutathione Peroxidase/metabolism
  • Ion Channels/genetics
  • Ion Channels/metabolism
  • Lauric Acids/metabolism
  • Lauric Acids/toxicity*
  • Lipid Peroxidation/drug effects
  • Liver/drug effects*
  • Liver/enzymology
  • Liver/metabolism
  • Liver/pathology
  • Mitochondrial Proteins/genetics
  • Mitochondrial Proteins/metabolism
  • Mitochondrial Proton-Translocating ATPases/genetics
  • Mitochondrial Proton-Translocating ATPases/metabolism
  • NADH Dehydrogenase/genetics
  • NADH Dehydrogenase/metabolism
  • Oxidative Stress/drug effects
  • PPAR alpha/genetics
  • PPAR alpha/metabolism
  • Proto-Oncogene Proteins c-bcl-2/genetics
  • Proto-Oncogene Proteins c-bcl-2/metabolism
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Random Allocation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Superoxide Dismutase/metabolism
  • Zebrafish/metabolism*
18760846 Full text @ Aquat. Toxicol.
The effects of acute perfluorododecanoic acid (PFDoA) exposure on the induction of oxidative stress and alteration of mitochondrial gene expression were studied in the livers of female zebrafish (Danio rerio). Female zebrafish were exposed to PFDoA via a single intraperitoneal injection (0, 20, 40, or 80mug PFDoA/g body weight) and were then sacrificed 48h, 96h, or seven days post-PFDoA administration. PFDoA-treated fish exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. Glutathione (GSH) content and catalase (CAT) activity decreased significantly at 48h post-injection while superoxide dismutase (SOD) activity was initially decreased at 48h post-injection but was then elevated by seven days post-injection. The activity of glutathione peroxidase (GPx) increased at 48h and seven days compared to control fish, although the increased level at seven days post-injection was decreased compared to the level at 48h post-injection. Lipid peroxidation levels were increased at seven days post-injection, while no apparent induction was observed at 48h or 96h post-injection. The mRNA expression of medium-chain fatty acid dehydrogenase (MCAD) was induced, while the transcriptional expression of liver fatty acid binding protein (L-FABP), peroxisome proliferating activating receptor alpha (PPARalpha), carnitine palmitoyl-transferase I (CPT-I), uncoupling protein 2 (UCP-2), and Bcl-2 were significantly inhibited. Furthermore, the transcriptional expression of peroxisomal fatty acyl-CoA oxidase (ACOX), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain acyl-CoA dehydrogenase (LCAD) did not exhibit significant changes following PFDoA treatment. No significant changes were noted in the transcriptional expression of genes involved in mitochondrial respiratory chain and ATP synthesis, including cytochrome c oxidase subunit I (COXI), NADH dehydrogenase subunit I (NDI), and ATP synthase F0 subunit 6 (ATPo6). These results demonstrate that turbulence of fatty acid beta-oxidation and oxidative stress responses were involved in the PFDoA-induced hepatotoxicity.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes