Asset Details
Do you wish to reserve the book?
Tricyclic antidepressants induce liver inflammation by targeting NLRP3 inflammasome activation
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Tricyclic antidepressants induce liver inflammation by targeting NLRP3 inflammasome activation
Do you wish to request the book?
Tricyclic antidepressants induce liver inflammation by targeting NLRP3 inflammasome activation
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Tricyclic antidepressants induce liver inflammation by targeting NLRP3 inflammasome activation
2023
Overview
Background
Idiosyncratic drug-induced liver injury (IDILI) is common in hepatology practices and, in some cases, lethal. Increasing evidence show that tricyclic antidepressants (TCAs) can induce IDILI in clinical applications but the underlying mechanisms are still poorly understood.
Methods
We assessed the specificity of several TCAs for NLRP3 inflammasome via MCC950 (a selective NLRP3 inhibitor) pretreatment and
Nlrp3
knockout (
Nlrp3
−/−
) BMDMs. Meanwhile, the role of NLRP3 inflammasome in the TCA nortriptyline-induced hepatotoxicity was demonstrated in
Nlrp3
−/−
mice.
Results
We reported here that nortriptyline, a common TCA, induced idiosyncratic hepatotoxicity in a NLRP3 inflammasome-dependent manner in mildly inflammatory states. In parallel in vitro studies, nortriptyline triggered the inflammasome activation, which was completely blocked by
Nlrp3
deficiency or MCC950 pretreatment. Furthermore, nortriptyline treatment led to mitochondrial damage and subsequent mitochondrial reactive oxygen species (mtROS) production resulting in aberrant activation of the NLRP3 inflammasome; a selective mitochondrial ROS inhibitor pretreatment dramatically abrogated nortriptyline-triggered the NLRP3 inflammasome activation. Notably, exposure to other TCAs also induced aberrant activation of the NLRP3 inflammasome by triggering upstream signaling events.
Conclusion
Collectively, our findings revealed that the NLRP3 inflammasome may act as a crucial target for TCA agents and suggested that the core structures of TCAs may contribute to the aberrant activation of NLRP3 inflammasome induced by them, an important factor involved in the pathogenesis of TCA-induced liver injury.
DBhggTBWtuReWsEtfqqAGm
Video Abstract
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Antidepressive Agents, Tricyclic - adverse effects
/ Biomedical and Life Sciences
/ Cellular signal transduction
/ Chemical and Drug Induced Liver Injury
/ Cytokines and Growth Factors
/ Enzymes
/ Ethylenediaminetetraacetic acid
/ Furans
/ Idiosyncratic hepatotoxicity
/ Liver
/ Mice
/ NLR Family, Pyrin Domain-Containing 3 Protein
/ NLRP3
/ Nortriptyline - adverse effects
/ Toxicity
