Cardinale D, Colombo A, Bacchiani G, Tedeschi I, Meroni CA, Veglia F, Civelli M, Lamantia G, Colombo N, Curigliano G, Fiorentini C, Cipolla CM. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;131:1981–8.

Article  PubMed  CAS  Google Scholar 

Swain S, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97:2869–79.

Article  PubMed  CAS  Google Scholar 

Lyon AR, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS): Developed by the task force on cardio-oncology of the European Society of Cardiology (ESC). Eur Heart J. 2022;43(41):4229–361.

Article  PubMed  Google Scholar 

Cova D, De Angelis L, Monti E, Piccinini F. Subcellular distribution of two spin trapping agents in rat heart: possible explanation for their different protective effects against doxorubicin-induced cardiotoxicity. Free Radic Res Commun. 1992;15:353–60.

Article  PubMed  CAS  Google Scholar 

Zhang S, Liu X, Bawa-Khalfe T, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 2012;18:1639–42.

Article  PubMed  Google Scholar 

Yang F, Teves SS, Kemp CJ, Henikoff S. Doxorubicin, DNA torsion, and chromatin dynamics. Biochim Biophys Acta. 2014;1845:84–9.

PubMed  CAS  Google Scholar 

Sardão VA, Oliveira PJ, Holy J, Oliveira CR, Wallace KB. Doxorubicin-induced mitochondrial dysfunction is secondary to nuclear p53 activation in H9c2 cardiomyoblasts. Cancer Chemother Pharmacol. 2009;64:811–2.

Article  PubMed  Google Scholar 

Davies KJ, Doroshow JH. Redox cycling of anthracyclines by cardiac mitochondria. I. Anthracycline radical formation by NADH dehydrogenase. J Biol Chem. 1986;261(7):3060–7.

Doroshow JH, Davies KJ. Redox cycling of anthracyclines by cardiac mitochondria. II. Formation of superoxide anion, hydrogen peroxide, and hydroxyl radical. J Biol Chem. 1986;261(7):3068–74.

Ichikawa Y, Ghanefar M, Bayeva M, Wu R, Khechaduri A, Naga Prasad SV, Mutharasan RK, Naik TJ, Ardehali H. Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J Clin Invest. 2014;124:617–30.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Lebrecht D, Setzer B, Ketelsen UP, Haberstroh J, Walker UA. Time-dependent and tissue-specific accumulation of mtDNA and respiratory chain defects in chronic doxorubicin cardiomyopathy. Circulation. 2003;108(19):2423–9.

Wallace KB, Sardão VA, Oliveira PJ. Mitochondrial Determinants of Doxorubicin-Induced Cardiomyopathy. Circ Res. 2020;126(7):926–41.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Varricchi G, Ameri P, Cadeddu C, Ghigo A, Madonna R, Marone G, Mercurio V, Monte I, Novo G, Parrella P, Pirozzi F, Pecoraro A, Spallarossa P, Zito C, Mercuro G, Pagliaro P, Tocchetti CG. Antineoplastic drug-induced cardiotoxicity: a redox perspective. Front Physiol. 2018;9:167.

Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007;13:1050–9.

Article  PubMed  CAS  Google Scholar 

Casares N, Pequignot MO, Tesniere A, Ghiringhelli F, Roux S, Chaput N, et al. Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. J Exp Med. 2005;202:1691–701.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Dhalla NS, Elmoselhi AB, Hata T, Makino N. Status of myocardial antioxidants in ischemia-reperfusion injury. Cardiovasc Res. 2000;47:446–56.

Article  PubMed  CAS  Google Scholar 

Bhagat A, et al. Doxorubicin-induced cardiotoxicity is mediated by neutrophils through release of neutrophil elastase. Front Oncol. 2022;12:947604.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Zitvogel L, Kepp O, Kroemer G. Decoding cell death signals in inflammation and immunity. Cell. 2010;140:798–804.

Article  PubMed  CAS  Google Scholar 

Kaczmarek A, Krysko O, Heyndrickx L, et al. TNF/TNF-R1 pathway is involved in doxorubicin-induced acute sterile inflammation. Cell Death Dis. 2013;4:e961.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ma Y, Zhang X, Bao H, Mi S, Cai W, Yan H, Wang Q, Wang Z, Yan J, Fan G, Lindsey ML, Hu Z. Toll-like receptor (TLR) 2 and TLR4 differentially regulate doxorubicin induced cardiomyopathy in mice. PLoS One. 2012;7:e40763.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Krysko DV, Kaczmarek A, Krysko O, Heyndrickx L, Woznicki J, Bogaert P, Cauwels A, Takahashi N, Magez S, Bachert C, Vandenabeele P. TLR-2 and TLR-9 are sensors of apoptosis in a mouse model of doxorubicin-induced acute inflammation. Cell Death Differ. 2011;18:1316–25.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Wang L, Chen Q, Qi H, Wang C, Wang C, Zhang J, Dong L. Doxorubicin-induced systemic inflammation is driven by upregulation of toll-like mediators of inflammation receptor TLR4 and endotoxin leakage. Cancer Res. 2016;76:6631–42.

Article  PubMed  CAS  Google Scholar 

Nozaki N, Shishido T, Takeishi Y, Kubota I. Modulation of doxorubicin induced cardiac dysfunction in toll-like receptor-2-knockout mice. Circulation. 2004;110:2869–74.

Article  PubMed  CAS  Google Scholar 

Yu L. Feng Z (2018) The role of toll-like receptor signaling in the progression of heart failure. Mediators Inflamm. 2018;1:9874109.

Google Scholar 

Medzhitov R, Preston-Hurlburt P, Janeway C. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997;399:394–7.

Article  Google Scholar 

Aggarwal B. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol. 2003;3:745–56.

Article  PubMed  CAS  Google Scholar 

Maayah ZH, et al. Resveratrol reduces cardiac NLRP3-inflammasome activation and systemic inflammation to lessen doxorubicin-induced cardiotoxicity in juvenile mice. FEBS Lett. 2021;595(12):1681–95.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Swanson KV, Deng M, Ting JPY. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019;19(8):477–89.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Sauter KA, Wood LJ, Wong J, Iordanov M, Magun BE. Doxorubicin and daunorubicin induce processing and release of interleukin-1β through activation of the NLRP3 inflammasome. Cancer Biol Ther. 2011;11(12):1008–16.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Yang F, et al. Pyroptosis and pyroptosis-inducing cancer drugs. Acta Pharmacol Sin. 2022;43(10):2462–73.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Sun Z, Lu W, Lin N, Lin H, Zhang J, Ni T, Meng L, Zhang C, Guo H. Dihydromyricetin alleviates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome through activation of SIRT1. Biochem Pharmacol. 2020;175:113888.

Article  PubMed  CAS  Google Scholar 

Jadapalli JK, Wright GW, Kain V, Sherwani MA, Sonkar R, Yusuf N, et al. Doxorubicin triggers splenic contraction and irreversible dysregulation of COX and LOX that alters the inflammation-resolution program in the myocardium. Am J Physiol Heart Circ. 2018;315(5):H1091–100.

Article  CAS  Google Scholar 

Buoncervello M, et al. Inflammatory cytokines associated with cancer growth induce mitochondria and cytoskeleton alterations in cardiomyocytes. J Cell Physiol. 2019;234(11):20453–68.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Stein-Merlob AF, Ganatra S, Yang EH. T-cell Immunotherapy and Cardiovascular Disease. Heart Fail Clin. 2022;18(3):443–54.

Article  PubMed