Antiresistin Neutralizing Antibody Alleviates Doxorubicin-Induced Cardiac Injury in Mice

Abstract

Background. Resistin is closely related to cardiovascular diseases, and this study is aimed at examining the role of resistin in doxorubicin- (DOX-) induced cardiac injury. Methods. First, 48 mice were divided into 2 groups and treated with saline or DOX, and the expression of resistin at different time points was examined ( $N=24$ ). A total of 40 mice were pretreated with the antiresistin neutralizing antibody (nAb) or isotype IgG for 1 hour and further administered DOX or saline for 5 days. The mice were divided into 4 groups: saline-IgG, saline-nAb, DOX-IgG, and DOX-nAb ( $N=10$ ). Cardiac injury, cardiomyocyte apoptosis, inflammatory factors, and the biomarkers of M1 and M2 macrophages in each group were analyzed. Result. DOX administration increased the expression of resistin. DOX treatment exacerbated the loss of body and heart weight and cardiac vacuolation in mice. The antiresistin nAb reversed these conditions, downregulated the expression of myocardial injury markers, and decreased apoptosis. In addition, the antiresistin nAb decreased p65 pathway activation, decreased M1 macrophage differentiation and the expression of related inflammatory factors, and increased M2 macrophage differentiation and the expression of related inflammatory factors. Conclusion. The antiresistin nAb protected against DOX-induced cardiac injury by reducing cardiac inflammation and may be a promising target to relieve DOX-related cardiac injury.