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. 2023 Nov 20;24(22):16545. doi: 10.3390/ijms242216545

Figure 2.

Figure 2

Proposed mechanism of cisplatin-induced cochlear inflammation. Following its entry into the cochlea and uptake by cells via either simple or facilitated diffusion, cisplatin induces an inflammatory response through various signaling pathways, including TLR4–NF-κB activation, TLR4–NF-κB–NLRP3 inflammasome activation, NOX3–NF-κB activation, NOX3–STAT1 activation, XO–NF-κB/STAT1 activation, reductions in antioxidant enzyme levels, STAT3 inhibition, and mast cell degranulation. The upregulation of pro-inflammatory mediators in the cochlea leads to the infiltration and activation of macrophages. Abbreviations: COX-2, cyclooxygenase 2; CTR1, copper-like transporter-1; CXCL1, chemokine (C-X-C motif) ligand 1; IL-1β, interleukin-1β; IL-18, interleukin-18; IL-6, interleukin-6; iNOS, inducible nitric oxide synthase; NF-κB, nuclear factor kappa B; NLRP3, NOD-like receptor protein 3; NOX3, NADPH oxidase 3; OCT2, organic cation transporter-2; ROS, reactive oxygen species; STAT1, signal transducer and activator of transcription-1; STAT3, signal transducer and activator of transcription-3; TNF-α, tumor necrosis factor-alpha; TLR4, Toll-like receptor 4; TMC1, transmembrane channel-like protein 1; XO, xanthine oxidase. This figure was created using BioRender.com (accessed on 16 November 2023).