Isoniazid promotes the anti-inflammatory response in zebrafish associated with regulation of the PPARγ/NF-κB/AP-1 pathway.

OBJECTIVE:Zebrafish inflammation models were used to evaluate the anti-inflammatory activity of isoniazid (INH) and preliminarily investigate the underlying mechanism. METHODS: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 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). RESULTS: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 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. CONCLUSION: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 duanyu1670 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.

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