ZFIN ID: ZDB-PUB-191223-1
Isoniazid promotes the anti-inflammatory response in zebrafish associated with regulation of the PPARγ/NF-κB/AP-1 pathway
Zhang, Y., Wang, C., Jia, Z.L., Ma, R.J., Wang, X.F., Chen, W.Y., Liu, K.C.
Date: 2019
Source: Chemico-biological interactions   316: 108928 (Journal)
Registered Authors: Wang, Chao
Keywords: Anti-Inflammatory effect, Isoniazid, Zebrafish
MeSH Terms:
  • Animals
  • Cyclooxygenase 2/genetics
  • Cyclooxygenase 2/metabolism
  • Cytokines/genetics
  • Cytokines/metabolism*
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Female
  • Interleukin-1beta/genetics
  • Interleukin-1beta/metabolism
  • Isoniazid/pharmacology*
  • Lipopolysaccharides/toxicity
  • Male
  • NF-kappa B/metabolism
  • PPAR gamma/metabolism
  • Reactive Oxygen Species/metabolism
  • Signal Transduction/drug effects*
  • Transcription Factor AP-1/metabolism
  • Transforming Growth Factor beta/genetics
  • Transforming Growth Factor beta/metabolism
  • Zebrafish/metabolism
PubMed: 31857089 Full text @ Chem. Biol. Interact.
Zebrafish inflammation models were used to evaluate the anti-inflammatory activity of isoniazid (INH) and preliminarily investigate the underlying mechanism.
Local, acute, and systemic zebrafish inflammation models were established by tail cutting, copper sulfate (CuSO4), and lipopolysaccharide (LPS) endotoxin treatments, respectively, to evaluate the anti-inflammatory activity of INH. Zebrafish in the inflammatory state were exposed to different concentrations of INH (1, 2, and 4 mM) for 72 h to observe changes in the migration and accumulation of inflammatory cells and measure the reactive oxygen species (ROS) content in zebrafish after INH treatment. The transcription levels of inflammation-related genes in zebrafish from all groups were measured using real-time polymerase chain reaction (RT-PCR).
Compared to those observed in the control inflammation model group, the numbers of migrated and accumulated inflammatory cells in zebrafish in the INH-treated group significantly decreased. INH significantly decreased the ROS content induced by LPS. Compared to that observed in the LPS model group, INH at 1 and 2 mM significantly increased the expression of PPARγ and inhibited the expression of NF-κB, iκbαa, and AP-1 as well as the inflammatory factors TNF-ɑ, TGF-β, IL-1b, and COX-2.
In this study, different zebrafish inflammation models were used to confirm that INH has anti-inflammatory activity. The associated mechanism may occur through the inhibition of ROS release, activation of PPARγ expression, inhibition of the transcriptional regulatory activity of NF-κB and AP-1, and reduction of INH inflammatory factor expression to relieve inflammation. The results of this study provide references for the clinical application of INH.