NLRP3 inflammasome as a therapeutic target in doxorubicin-induced cardiotoxicity: role of phytochemicals

FIGURE 1. The main pathological mechanisms of doxorubicin-induced cardiotoxicity. Doxorubicin-induced cardiotoxicity involves multiple pathological mechanisms. The main can include oxidative stress, apoptosis, ferroptosis, pyroptosis, autophagy, inflammation, endoplasmic reticulum stress, epigenetics, Ca2+ overload, disturbed energy metabolism and mitochondrial dysfunction (Created with BioRender.com).

FIGURE 2. The activation process of NLRP3 inflammasome. The activation of NLRP3 inflammasome depends on two main signals. First is the “priming” signal. This signal is primarily mediated by a variety of PRRs, including TLRs. These receptors recognize PAMPs or DAMPs, thereby triggering the nuclear translocation of NF-κB. This process subsequently induces the transcription of NLRP3, IL-1β, and IL-18. The next is the “triggering” signal. The signal promotes NLRP3 oligomerization and NLRP3 interacts with ASC. ASC binds to pro-caspase-1 to form the NLRP3 inflammasome. Pro-caspase-1 is cleaved into active caspase-1, which activates pro-IL-1β, pro-IL-18 and GSDMD. Activated NT-GSDMD forms membrane pores, releasing IL-1β and IL-18 and inducing pyroptosis. This signal is triggered by factors like ion flow (K+ efflux, Na+ influx), ATP, pore-forming toxins, particulate matter and silica crystals (Created with BioRender.com). (PRRs, pattern recognition receptors; PAMPs, pathogen-associated molecular patterns; DAMPs, damage-associated molecular patterns; TLRs, toll-like receptors; NF-κB, nuclear factor kappa B; IκK, IkappaB kinase; IL-1β, interleukin-1beta; NLRP3, nod-like receptor family pyrin…