Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/119545
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Type: Journal article
Title: Flavonoid genistein protects bone marrow sinusoidal blood vessels from damage by methotrexate therapy in rats
Author: Hassanshahi, M.
Su, Y.
Khabbazi, S.
Fan, C.
Chen, K.
Wang, J.
Qian, A.
Howe, P.
Yan, D.
Zhou, H.
Xian, C.
Citation: Journal of Cellular Physiology, 2019; 234(7):11276-11286
Publisher: Wiley Online Library
Issue Date: 2019
ISSN: 0021-9541
1097-4652
Statement of
Responsibility: 
Mohammadhossein Hassanshahi, Yu‐Wen Su, Samira Khabbazi, Chia‐Ming Fan, Ke‐Ming Chen, Ju‐Fang Wang, Airong Qian, Peter R. Howe, De‐Wen Yan, Hou‐De Zhou, Cory J. Xian
Abstract: Cancer chemotherapy can cause significant damage to the bone marrow (BM) microvascular (sinusoidal) system. Investigations must now address whether and how BM sinusoidal endothelial cells (SECs) can be protected during chemotherapy. Herein we examined the potential protective effects of genistein, a soy-derived flavonoid, against BM sinusoidal damage caused by treatment with methotrexate (MTX). The groups of young adult rats were gavaged daily with genistein (20 mg/kg) or placebo. After 1 week, rats also received daily injections of MTX (0.75 mg/kg) or saline for 5 days and were killed after a further 4 days. Histological analyses showed that BM sinusoids were markedly dilated ( p < 0.001) in the MTX-alone group but were unaffected or less dilated in the genistein+MTX group. In control rats, genistein significantly enhanced expression of vascular endothelial growth factor (VEGF; p < 0.01), particularly in osteoblasts, and angiogenesis marker CD31 ( p < 0.001) in bone. In MTX-treated rats, genistein suppressed MTX-induced apoptosis of BM SECs ( p < 0.001 vs MTX alone group) and tended to increase expression of CD31 and VEGF ( p < 0.05). Our in vitro studies showed that genistein in certain concentrations protected cultured SECs from MTX cytotoxic effects. Genistein enhanced tube formation of cultured SECs, which is associated with its ability to induce expression of endothelial nitric oxide synthase and production of nitric oxide. These data suggest that genistein can protect BM sinusoids during MTX therapy, which is associated, at least partially, with its indirect effect of promoting VEGF expression in osteoblasts and its direct effect of enhancing nitric oxide production in SECs.
Keywords: angiogenesis; apoptosis; bone marrow sinusoidal endothelial cells (BM SECs); genistein
Rights: © 2018 Wiley Periodicals, Inc.
RMID: 0030106018
DOI: 10.1002/jcp.27785
Grant ID: http://purl.org/au-research/grants/nhmrc/508046
http://purl.org/au-research/grants/nhmrc/508047
http://purl.org/au-research/grants/nhmrc/1010752
http://purl.org/au-research/grants/nhmrc/1127396
http://purl.org/au-research/grants/nhmrc/1042105
Appears in Collections:Psychology publications

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