Doxorubicin Impairs Skeletal Muscle Regeneration by Dysregulating the Early Inflammatory Response

For patients with certain types of malignant tumors, chemotherapy is administered before and/or after surgery. However, the potential impact of chemotherapeutic agents on tissue regeneration and wound healing after surgery is not fully understood. In this study, we examined the possible effects of doxorubicin (DOX), one of the most widely used chemotherapeutic agents, on muscle regeneration using a mouse muscle injury model. Histologic analysis revealed that DOX significantly impairs muscle regeneration, resulting in reduced muscle mass and fibrosis when administered during the early phase of the inflammatory response following injury. Contrary to our initial assumption, DOX administration did not suppress the proliferation of satellite cells or the expression of myogenic transcripts. Rather, DOX delayed the infiltration of immune cells to the injury site, which most likely resulted in insufficient clearance of necrotic tissues and prolonged immune cell infiltration. Taken together, our findings reveal an unrecognized effect of DOX on muscle regeneration and underscore the critical role of the early inflammatory response in initiating proper muscle regeneration after injury.