Effect of histidine on sorafenib-induced vascular damage: Analysis using novel medaka fish model.
Effect of histidine on sorafenib-induced vascular damage: Analysis using novel medaka fish model.
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DOI：
10.1016/j.bbrc.2018.01.057
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发表时间：
2018-02
影响因子：
3.1
通讯作者：
Yoko Shinagawa-Kobayashi;Kenya Kamimura;Ryo Goto;Kohei Ogawa;Ryosuke Inoue;Takeshi Yokoo;Norihiro Sakai;Takuro Nagoya;Akira Sakamaki;Satoshi Abe;S. Sugitani;M. Yanagi;K. Fujisawa;Yoshizu Nozawa;Naoto Koyama;H. Nishina;M. Furutani-Seiki;I. Sakaida;S. Terai
中科院分区：
文献类型：
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作者：
Yoko Shinagawa-Kobayashi;Kenya Kamimura;Ryo Goto;Kohei Ogawa;Ryosuke Inoue;Takeshi Yokoo;Norihiro Sakai;Takuro Nagoya;Akira Sakamaki;Satoshi Abe;S. Sugitani;M. Yanagi;K. Fujisawa;Yoshizu Nozawa;Naoto Koyama;H. Nishina;M. Furutani-Seiki;I. Sakaida;S. Terai
背景索拉非尼（SFN）是一种抗血管生成的化疗药物，可提高肝细胞癌（HCC）患者的生存率;其副作用，包括血管损伤，如手足综合征（HFS），是导致治疗中断的主要原因。我们以前曾报道，通过摄入干鲣鱼肉汤（DBB）来维持外周血流量，可显著预防HFS并延长给药期。DBB中所含的氨基酸可能有助于其作用，但其机制尚未阐明。我们假设，组氨酸，DBB中所含的氨基酸中最大的组成部分，SFN诱导的血管损伤的影响，并评估这种可能性使用一种新的青鳉鱼模型。方法建立荧光显微镜下可见的转fli：：GFP基因青鳉鱼模型。我们给鱼喂食SFN，有和没有组氨酸，以比较不同喂食模型之间的血流和血管结构。测量每条鱼的血管横截面积以确定血管直径的变化。结果我们的研究结果表明，SFN喂养青鳉发展了一个狭窄的血管直径。此外，这种缩小被抵消了组氨酸的青鳉饮食。我们没有观察到组氨酸对切割血管的再生或对内皮细胞和HCC细胞系的细胞生长的积极作用。结论我们证明了青鳉模型评估特定化学物质给药后血管变化的有效性。我们的研究结果表明，SFN通过缩小外周血管直径引起血管损伤，组氨酸有效地抵消了这些变化，以维持血流。
Background Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs survival of patients with hepatocellular carcinoma (HCC); its side effects, including vascular damages such as hand-foot syndrome (HFS), are a major cause of therapy discontinuation. We previously reported that maintenance of peripheral blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and prolonged the administration period. The amino acids contained in DBB probably contribute to its effects, but the mechanism has not been clarified. We hypothesized that histidine, the largest component among the amino acids contained in DBB, has effects on SFN-induced vascular damage, and evaluated this possibility using a novel medaka fish model. Methods The fli:: GFP transgenic medaka fish model has a fluorescently visible systemic vasculature. We fed the fish with SFN with and without histidine to compare blood flow and vascular structure among the differently fed models. The vascular cross-sectional area of each fish was measured to determine vascular diameter changes. Results Our results demonstrated that SFN-fed medaka developed a narrower vascular diameter. In addition, this narrowing was counteracted by addition of histidine to the medaka diet. We observed no positive effect of histidine on regeneration of cut vessels or on cell growth of endothelial cells and HCC cell lines. Conclusion We proved the efficacy of the medaka model to assess vascular changes after administration of specific chemicals. And our results suggest that SFN causes vascular damage by narrowing peripheral vessel diameter, and that histidine effectively counteracts these changes to maintain blood flow.