Effect of histidine on sorafenib-induced vascular damage: Analysis using novel medaka fish model

• Published in: Biochemical and biophysical research communications Vol. 496; no. 2; pp. 556 - 561
• Main Authors: Shinagawa-Kobayashi, Yoko, Kamimura, Kenya, Goto, Ryo, Ogawa, Kohei, Inoue, Ryosuke, Yokoo, Takeshi, Sakai, Norihiro, Nagoya, Takuro, Sakamaki, Akira, Abe, Satoshi, Sugitani, Soichi, Yanagi, Masahiko, Fujisawa, Koichi, Nozawa, Yoshizu, Koyama, Naoto, Nishina, Hiroshi, Furutani-Seiki, Makoto, Sakaida, Isao, Terai, Shuji
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.02.2018
• Subjects: 60 APPLIED LIFE SCIENCES; BLOOD FLOW; Hand-foot syndrome; HEPATOMAS; HISTIDINE; Medaka; SIDE EFFECTS; Sorafenib; Vascular damage; Medaka; Histidine; Vascular damage; Sorafenib; Hand-foot syndrome
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.01.057

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. 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. 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. 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. [Display omitted] •Sorafenib decreased blood flow in the vasculature by narrowing the vascular diameter.•Histidine maintained the blood flow by dilating the vascular diameter of the existing vessel.•Histidine was useful for managing the sorafenib related vascular damage.•No positive effect of histidine was seen on the tumor progression or on the novel regenerating vessels.•A fli::GFP transgenic medaka is useful for analyzing the vascular changes under the administration of these chemicals.