The role of NLRP3 inflammasome in psychotropic drug-induced hepatotoxicity.

ABSTRACT: Increased medical application of psychotropic drugs raised attention concerning their toxicological effects. In fact, more than 160 psychotropic drugs including antidepressants and antipsychotics, have been shown to cause liver side effects, but the underlying mechanisms are still poorly understood. Here, we discovered that fluoxetine, a common antidepressant, was specifically sensed by NLRP3 inflammasome, whose subsequent activation resulted in the maturation of caspase-1 and IL-1β, as well as gasdermin D (GSDMD) cleavage, which could be completely abrogated by a selective NLRP3 inhibitor MCC950 or Nlrp3 knockout (Nlrp3^-/-). Mechanistically, mitochondrial damage and the subsequent mitochondrial reactive oxygen species (mtROS) accumulation were crucial upstream signaling events

SUBMITTER: Mu W 

PROVIDER: S-EPMC9271040 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature