Fig. 1
Schematic representation of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy. DOX induces overgeneration of ROS and RNS and leads to oxidative stress by activating Nrf2/Keap1/ARE, SIRT1/p66Shc, Sirt1/PPAR/PGC-1α pathway as well as interfering with NOS, NOX and Fe2+ signaling. DOX increases the secretion and release of inflammatory cytokines by acting on NLRP3/caspase-1/GSDMD, HMGB1/TLR4/MAPKs/NF-κB, mTOR/TFEB/NF-κB pathway, and further cause cell and tissue damage. DOX: doxorubicin, ROS: reactive oxygen species, RNS: reactive nitrogen species, Sirt1: Silent information regulator 1, Nrf2: Nuclear factor E2-related factor 2, Keap1: kelch-like ECH associated protein 1, sMaf: small Maf proteins, ARE: antioxidant response element, NQO-1: NAD(P)H quinone oxidoreductase-1, SOD: superoxide dismutase, GPX: Glutathione peroxidase 4, HO-1: heme oxygenase-1, P66Shc: The 66-kDa Src homology 2 domain-containing protein, NOX: NAD(P)H oxidase, iNOS: inducible nitric oxide synthas, eNOS: endothelial nitric oxide synthase, PPAR: Peroxisome proliferator-activated receptors, PGC-1α: PPAR coactivator 1α, NRF-1: nuclear respiratory factor 1, TFAM: mitochondrial transcription factor A, Acot1: acyl-coenzyme A thioesterase 1, IRP: iron regulins protein, FtMt: Mitochondrial ferritin, TfR: transferrin receptor, ABCB8: ATP-binding cassette transporter protein B8, NLRP3: nucleotide-binding domain-like receptor protein 3, GSDMD: gasdermin D, GSDME: gasdermin E, MyD88: myeloid differentiation factor 88, IRF3: interferon regulator 3, NF-κB: nuclear factor-κB, TLR: Toll-like receptors, TNF-α: tumor necrosis factor-α, IL: interleukin, IKK: IκB kinase, mTOR: Mechanistic target of rapamycin, TFEB: transcription factor EB