- Title
- Flavonoid genistein protects bone marrow sinusoidal blood vessels from damage by methotrexate therapy in rats
- Creator
- Hassanshahi, Mohammadhossein; Su, Yu-Wen; Xian, Cory J.; Khabbazi, Samira; Fan, Chia-Ming; Chen, Ke-Ming; Wang, Ju-Fang; Qian, Airong; Howe, Peter R.; Yan, De-Wen; Zhou, Hou-De
- Relation
- NHMRC.1042105 http://purl.org/au-research/grants/nhmrc/1042105
- Relation
- Journal of Cellular Physiology Vol. 234, Issue 7, p. 11276-11286
- Publisher Link
- http://dx.doi.org/10.1002/jcp.27785
- Publisher
- John Wiley & Sons
- Resource Type
- journal article
- Date
- 2019
- Description
- 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.
- Subject
- angiogenesis; apoptosis; bone marrow sinusoidal endothelial cells (BM SECs); genistein; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1424900
- Identifier
- uon:38163
- Identifier
- ISSN:0021-9541
- Rights
- This is the peer reviewed version of the following article: Hassanshahi, Mohammadhossein; Su, Yu-Wen; Xian, Cory J.; Khabbazi, Samira; Fan, Chia-Ming; Chen, Ke-Ming; Wang, Ju-Fang; Qian, Airong; Howe, Peter R.; Yan, De-Wen; Zhou, Hou-De. “Flavonoid genistein protects bone marrow sinusoidal blood vessels from damage by methotrexate therapy in rats”. Journal of Cellular Physiology Vol. 234, Issue 7, p. 11276-11286 (2019), which has been published in final form at http://dx.doi.org/10.1002/jcp.27785. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
- Language
- eng
- Full Text
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