Upregulation of Nrf2-regulated gene expression by tBHQ alleviates cyclophosphamide-induced hematotoxicity in mice

doi:10.5246/jcps.2014.01.006

Journal of Chinese Pharmaceutical Sciences

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Upregulation of Nrf2-regulated gene expression by tBHQ alleviates cyclophosphamide-induced hematotoxicity in mice

Linling Que, Xinzhu Wang, Pengzhan Qian, Baoshan Cao, Kui Wang, Siwang Yu^*

1. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Department of Oncology, Cancer Center, Peking University Third Hospital, Beijing 100191, China

Received:2013-06-17 Revised:2013-07-10 Online:2014-01-23 Published:2014-01-22
Contact: Siwang Yu*
About author:*Corresponding author. Tel.: +86-10-82801539; E-mail: swang_yu@bjmu.edu.cn
Supported by:
National Natural Science Foundation (Grant No. 81272468 and 21001011) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, Ministry of Education.

Abstract

Abstract:

Hematological toxicity (bone marrow suppression) is the most common dose-limiting adverse effect of chemotherapies. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal coordinator of cellular defensive responses against chemical insults in many tissues including bone marrow. In the present study, the effects of tert-butylhydroquinone (tBHQ) on the expression of Nrf2-regulated genes in peripheral blood cells and cyclophosphamide (CTX)-induced hematotoxicity in mice were investigated. CTX induced apoptosis of peripheral blood nucleated cells and leukopenia in mice, accompanied by mobilization of bone marrow hematopoietic cells. tBHQ treatment induced the expression of Nrf2-regulated genes such as heme oxygenase 1 (HO1) and glutamate-cysteine ligase catalytic subunit (GCLC) in RAW264.7 mouse macrophage cells and peripheral blood cells both in vitro and in vivo. Interestingly, pretreatment with tBHQ alleviated CTX-induced mouse peripheral blood cell apoptosis and leukopenia in vivo, indicating possible involvement of Nrf2 in the protection against CTX-induced hematotoxicity. This study provides new information on the chemotherapy-induced hematotoxicity, and suggests Nrf2 could serve as a target for the development of chemoprotectants against hematotoxicity.

Key words: Cyclophosphamide, Hematotoxicity, Peripheral blood cells, Bone marrow, tBHQ, Nrf2

CLC Number:

R915

Supporting:

Linling Que, Xinzhu Wang, Pengzhan Qian, Baoshan Cao, Kui Wang, Siwang Yu* . Upregulation of Nrf2-regulated gene expression by tBHQ alleviates cyclophosphamide-induced hematotoxicity in mice[J]. Journal of Chinese Pharmaceutical Sciences, DOI: 10.5246/jcps.2014.01.006.

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Upregulation of Nrf2-regulated gene expression by tBHQ alleviates cyclophosphamide-induced hematotoxicity in mice

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