Low‐intensity pulsed ultrasound alleviates doxorubicin‐induced cardiotoxicity via inhibition of S100a8/a9‐mediated cardiac recruitment of neutrophils

Doxorubicin (DOX)-induced cardiotoxicity limits its broad use as a chemotherapy agent. The development of effective and non-invasive strategies to prevent DOX-associated adverse cardiac events is urgently needed. We aimed examine whether how low-intensity pulsed ultrasound (LIPUS) plays protective role in DOX-induced cardiotoxicity. Male C57BL/6J mice were used establish models both acute chronic cardiomyopathy. Non-invasive LIPUS therapy was conducted for four consecutive days after DOX administration. Cardiac contractile function evaluated by echocardiography. Myocardial apoptosis, oxidative stress, fibrosis analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining, dihydroethidium (DHE) picrosirius red staining assays. RNA-seq analysis performed unbiasedly explore the possible downstream regulatory mechanisms. Neutrophil recruitment infiltration heart flow cytometry. S100a8/a9 inhibitor ABR-238901 utilized identify effect signaling. found that elicited great benefit on dysfunction models. Chronic administration increased serum creatine kinase lactate dehydrogenase levels, well myocardial all which significantly mitigated LIPUS. In addition, treatment prevented stress fibrosis. revealed partially reversed alterations gene expression induced DOX. Gene ontology (GO) downregulated genes between DOX-LIPUS DOX-Sham groups indicated inhibition neutrophil chemotaxis might be involved effects therapy. Flow cytometry illustrated inhibitory heart. Moreover, S100 calcium binding protein A8/A9 (S100a8/a9) identified potential key target showed similar against cardiomyopathy treatment. prevents through S100a8/a9-mediated heart, suggesting application cancer patients undergoing with