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Reactive Oxygen Species-Mediated Inflammation and Apoptosis in Hand-Foot Syndrome Induced by PEGylated Liposomal Doxorubicin

Authors Hu X, Dong M, Liang X, Liu Z, Li Q

Received 4 September 2020

Accepted for publication 28 December 2020

Published 18 January 2021 Volume 2021:16 Pages 471—480

DOI https://doi.org/10.2147/IJN.S280187

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang


Xiaolin Hu,1,2 Mengmeng Dong,2 Xiao Liang,2 Ziling Liu,1 Quanshun Li2

1Cancer Center, The First Hospital of Jilin University, Changchun 130012, People’s Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, People’s Republic of China

Correspondence: Quanshun Li; Ziling Liu Tel +86-431-85155201
Fax +86-431-85155200
Email quanshun@jlu.edu.cn; ziling@jlu.edu.cn

Background: Doxil® (PEGylated liposomal doxorubicin, PLD) has been widely used in cancer treatment due to its excellent therapeutic efficacy, but it can simultaneously cause severe adverse effects such as hand-foot syndrome (HFS). To date, the pathophysiologic mechanism of HFS development induced by PLD administration has not been well understood.
Materials and Methods: The histological features of skin lesion in PLD-induced HFS model were characterized by hematoxylin and eosin (H&E) staining and picrosirius red staining, and the induction of inflammation and apoptosis in the epidermal layer was detected by immunohistochemical and TUNEL staining. Moreover, the generation of reactive oxygen species (ROS) was determined to elucidate the potential mechanism of skin lesion in the development of HFS.
Results: The administration of PLD has been demonstrated to induce the histological damage of skin tissues including the destruction of collagen fibers and the induction of severe inflammation and apoptosis of epidermal cells. The mechanism was probably attributed to the accumulation of PLD in the skin tissues during the long-term circulation and further the induction of ROS to cause the oxidative damage of keratinocytes owing to the sustained release of doxorubicin from PLD.
Conclusion: The ROS generation induced by the administration of PLD has been identified to be a crucial factor in the development of HFS, which could be used as a potential therapeutic target to alleviate the HFS symptom of PLD administration.

Keywords: PEGylated liposomal doxorubicin, hand-foot syndrome, reactive oxygen species, skin lesion

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