Dexrazoxane Protects Against Hand–Foot Syndrome–Like Skin Damage in Pegylated Liposomal Doxorubicin‐Treated Mice

The anticancer drug pegylated liposomal doxorubicin (PLD) can cause hand-foot syndrome (HFS), a condition that develops in the palms and soles when pressure is frequently applied. Strategies to address HFS are insufficient. Dexrazoxane (DXZ) protects against doxorubicin-induced cardiotoxicity, possibly via reducing topoisomerase (Topo) IIβ levels in myocytes. Previously, we developed a rat model that used three tail-vein doses of PLD to induce HFS-like skin damage. In this study, we generated a simple mouse model of HFS-like skin damage using rubber fastening and PLD treatment to examine potential protective effects from DXZ. Male ddY mice received PLD (16.5 mg/kg) intravenously, with the flank skin compressed by a rubber band for 48 h. DXZ (50 and 250 mg/kg) was administered intraperitoneally twice prior to PLD. Skin tissues were removed on Day 12, fixed, and stained with hematoxylin-eosin to assess epidermal thickening. Western blotting identified the expression of γH2AX (a DNA damage marker) and the doxorubicin targets Topo IIα/β. After Day 8, DXZ (both concentrations) + PLD groups exhibited less skin damage than the PLD group. The PLD group showed greater epidermal layer thickening than both the control and DXZ + PLD groups. γH2AX and Topo IIβ expression increased in the back and flank regions of PLD-treated mice but was suppressed under DXZ + PLD treatment. Although not significant, Topo IIα expression followed an analogous pattern to Topo IIβ expression. In conclusion, we demonstrated that DXZ inhibited PLD-induced skin damage.