RRC ID 53892
著者 Shinagawa-Kobayashi Y, Kamimura K, Goto R, Ogawa K, Inoue R, Yokoo T, Sakai N, Nagoya T, Sakamaki A, Abe S, Sugitani S, Yanagi M, Fujisawa K, Nozawa Y, Koyama N, Nishina H, Furutani-Seiki M, Sakaida I, Terai S.
タイトル Effect of histidine on sorafenib-induced vascular damage: Analysis using novel medaka fish model.
ジャーナル Biochem Biophys Res Commun
Abstract 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.
巻・号 496(2)
ページ 556-561
公開日 2018-2-5
DOI 10.1016/j.bbrc.2018.01.057
PII S0006-291X(18)30063-9
PMID 29331379
MeSH Animals Antineoplastic Agents / adverse effects* Blood Flow Velocity / drug effects* Blood Vessels / drug effects* Blood Vessels / pathology* Carcinoma, Hepatocellular / drug therapy Histidine / pharmacology* Humans Liver Neoplasms / drug therapy Niacinamide / adverse effects Niacinamide / analogs & derivatives* Oryzias Phenylurea Compounds / adverse effects* Sorafenib
IF 2.985
引用数 5
リソース情報
メダカ fli1::GFP (TG1206) Kyoto-Cab