TB Research

Yes-associated protein inhibitor verteporfin rescues anti-tuberculosis drug-induced liver injury by downregulating NLRP3

Yifei Long, Xueying Li, Yue Liu, Mi Zhang, Fumin Feng

Abstract

The precise mechanism of underlying antituberculous drug-induced liver injury caused by tuberculosis during clinical treatment remains unknown. In this study, we investigated the impact of verteporfin (VP), a YAP inhibitor, on the expression of NLRP3 inflammasome-related factors in antituberculosis drug-induced liver injury (ADLI). After adaptive feeding, sixty male SPF Kunming mice aged 6-7 weeks were randomly assigned to different groups, and each group was administered the corresponding doses of drug solvents and inhibitors. The mRNA and protein expression levels of YAP, NLRP3, caspase-1, and IL-1β in serum were quantified using qPCR and ELISA techniques respectively; Western Blotting was employed to assess the protein levels of YAP and NLRP3 in liver tissue. The finds suggest that high expression of YAP is associated with antituberculosis drug-induced liver injury, and inhibiting its expression could reduce the level of NLRP3 inflammasome-related factors.

MeSH terms

  • Liver injury
  • Inflammasome
  • Drug
  • Pharmacology
  • Tuberculosis
  • Medicine
  • Verteporfin
  • Blot
  • Messenger RNA
  • Protein expression
  • Internal medicine