Doxorubicin primarily targets topoisomerase IIβ (Top2β) and induces DNA double-strand breaks.7 It also disrupts cardiac pro-survival pathway, the neuregulin/ErbB signalling which results in mitochondrial dysfunction and apoptosis. Since the three antiinflammatory drugs tested are all cyclooxygenase inhibitors, but only ibuprofen inhibits neutrophil infiltration, the latter mechanism is proposed as the primary basis for the observed protection. Elsevier Science Doxorubicin-induced cardiotoxicity is dose dependent. Epub 2018 Nov 16.Cell Physiol Biochem. The mechanism of doxorubicin is intercalated with the DNA and inhibits topoisomerase 2. Figure 5. Mechanism of doxorubicin cardiotoxicity evaluated by integrating multiple molecular effects into a biophysical model. The effects of DOX and its metabolite doxorubicinol (DOXL) on individual channels have been well characterized in isolation. Generally, doxorubicin toxicity is originated from the myocardium and then other organs are also ruined. 2020 Jun 30;53(2):201-215. doi: 10.5115/acb.19.236.Ouyang J, Yang M, Gong T, Ou J, Tan Y, Zhang Z, Li S.PLoS One. 2018 Dec;16(6):4457-4462. doi: 10.3892/etm.2018.6777. 2018 Jun 1;348:1-13. doi: 10.1016/j.taap.2018.04.009. Myofibrillar deterioration and intracellular calcium dysregulation are also important mechanisms commonly associated with doxorubicin-induced cardiac toxicity. Generally, doxorubicin toxicity is originated from the myocardium and then other organs are also ruined. Epub 2019 Sep 19.Trends Pharmacol Sci. Epub 2014 Feb 6.Amgalan D, Garner TP, Pekson R, Jia XF, Yanamandala M, Paulino V, Liang FG, Corbalan JJ, Lee J, Chen Y, Karagiannis GS, Sanchez LR, Liang H, Narayanagari SR, Mitchell K, Lopez A, Margulets V, Scarlata M, Santulli G, Asnani A, Peterson RT, Hazan RB, Condeelis JS, Oktay MH, Steidl U, Kirshenbaum LA, Gavathiotis E, Kitsis RN.Nat Cancer. Three nonsteroidal anti-inflammatory drugs, aspirin, ibuprofen and sulindac were tested for effects upon survival in the chronic mouse model of doxorubicin cardiotoxicity. 2014 Apr 5;728:107-18. doi: 10.1016/j.ejphar.2014.01.065. Clipboard, Search History, and several other advanced features are temporarily unavailable. The upregulated DRs may undergo clustering or engage their cognate ligands, thereby triggering a caspase cascade and ultimate apoptosis in cardiomyocytes. Epub 2018 Sep 19. doi: 10.1371/journal.pone.0235090. The mechanisms of doxorubicin-induced cardiotoxicity remain incompletely understood. 2014 Oct;35(10):520-36. doi: 10.1016/j.tips.2014.07.004. TRAIL enhances doxorubicin-induced cytotoxicity in… Figure 3. Please enable it to take advantage of the complete set of features! Ibuprofen-treated mice also lost less weight during the treatment period than all other doxorubicin injected animals (p less than 10(-6]. The present study was designed to further investigate any effect that ibuprofen might have on doxorubicin toxicity. Doxorubicin is utilized for anti-neoplastic treatment for several decades. 2002 Oct;50(4):277-84. doi: 10.1007/s00280-002-0485-8. Additionally, the age of the patients plays a role in susceptibility with younger patients having a greater risk for cardiotoxicity and heart failure years after treatment is complete. Graphical Abstract The cardiotoxic mechanism of doxorubicin (DOX) and pegylated liposomal DOX (PL-DOX). Unable to load your collection due to an error The utility of this drug is limited due to its side effects. Please enable it to take advantage of the complete set of features! TRAIL augments doxorubicin-induced alterations in… Figure 5. 2015 Nov;51(16):2314-20. doi: 10.1016/j.ejca.2015.07.031.