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

## TL;DR

Dexrazoxane reduces skin damage caused by a cancer drug in mice, potentially by protecting skin cells from DNA damage.

## Contribution

A new mouse model of hand-foot syndrome was developed, and dexrazoxane's protective effects against drug-induced skin damage were demonstrated.

## Key findings

- Dexrazoxane reduced epidermal thickening and skin damage in mice treated with pegylated liposomal doxorubicin.
- Dexrazoxane suppressed γH2AX and Topo IIβ expression in PLD-treated mice.
- The protective effect of dexrazoxane was observed at both tested doses (50 and 250 mg/kg).

## Abstract

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.