Pegylated liposomal doxorubicin (
PLD) has been widely used to treat
cancer. The adverse effects of
PLD noted in clinical practice, especially
hand-foot syndrome (HFS), are regarded as unique, and the management methods for them remain limited. This study was aimed at developing a feasible experimental model for translational medicine to solve this clinical issue by using skin fluorescent transgenic zebrafish. We established an optimal protocol for the administration of Lipo-Dox™, a
PLD in current clinical use, to the Tg(
k18:
dsred) zebrafish line expressing red fluorescence in keratinocytes. We made use of bodyweight, survival rate, gross observation, flssuorescent microscopic assessment, and pathological examination of the zebrafish to assess this model. The consecutive administration protocol of
PLD resulted in growth retardation of the zebrafish embryo and survival impairment, indicating establishment of a significant toxicity. We observed fin
necrosis and keratinocyte dissociation phenotypes in the
PLD-treated fish after consecutive administration. The skin toxicity induced by the Lipo-Dox injection was subsequently reversible, which might be compatible with a
clinical course of skin recovery after discontinuation of Lipo-Dox administration. Furthermore, we found that the number of intestinal goblet cells, an important marker of intestinal
inflammation, in the Lipo-Dox-injected zebrafish was markedly increased, accompanied by impaired mucosal integrity. The intestinal
inflammation induced by Lipo-Dox resembled the intestinal
mucositis the clinical patients suffered from after the administration of
PLD. In conclusion, we established a zebrafish model for
PLD-induced HFS. The intestinal
mucositis simultaneously noted in the
PLD-treated zebrafish validated the similarity of clinical courses after administration of
PLD. This model is easily assessable, efficient, and worthy for use in developing a new therapeutic protocol for prevention or treatment of HFS as well as intestinal
mucositis. Further clinical investigations to validate the correlation between human and zebrafish data are warranted.