研究者詳細 - 豊國　伸哉

論文 - 豊國　伸哉

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Molecular hydrogen ameliorates several characteristics of preeclampsia in the Reduced Uterine Perfusion Pressure (RUPP) rat model. 査読有り国際誌

Ushida T, Kotani T, Tsuda H, Imai K, Nakano T, Hirako S, Ito Y, Li H, Mano Y, Wang J, Miki R, Yamamoto E, Iwase A, Bando YK, Hirayama M, Ohno K, Toyokuni S, Kikkawa F

Free Radic Biol Med. pii: S0891-5849 巻 ( 16 ) 頁： 30978-9. 2016年10月

Non-thermal plasma prevents progression of endometriosis in mice. 査読有り

Ishida C, Mori M, Nakamura K, Tanaka H, Mizuno M, Hori M, Iwase A, Kikkawa F, Toyokuni S.

Free Radical Research 50 巻 ( 10 ) 頁： 1131-1139 2016年10月

Non-thermal plasma prevents progression of endometriosis in mice. 査読有り国際誌

Ishida C, Mori M, Nakamura K, Tanaka H, Mizuno M, Hori M, Iwase A, Kikkawa F, Toyokuni S

Free radical research 50 巻 ( 10 ) 頁： 1131 - 1139 2016年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Free Radical Research

Endometriosis is observed in ∼10% of reproductive age women. Ovarian endometriosis not only causes dysmenorrhea but also causes infertility and a high risk of adenocarcinoma. Due to its scattered nature, complete surgical resection is difficult. Endometriosis consists of glandular and stromal cells. Previously, we showed that endometrial stromal cells (ESCs) play a role in the protection against pathologic events caused by monthly repeated hemorrhage. Here, we undertook a preclinical study of non-thermal plasma (NTP) as a surgical treatment of endometriosis. Epithelial cells were most sensitive to NTP-activated medium in vitro, whereas ectopic ESCs were most resistant. We then transplanted excised uteruses into BALB/c mice from donors of the same strain with estradiol supplementation. Four weeks after the transplantation, we exposed NTP to each endometriotic lesion after laparotomy. Immunohistochemical analysis revealed that immediately after NTP exposure, epithelial cells exhibited significantly higher levels of nuclear immunostaining for 8-hydroxy-2′-deoxyguanosine than did stromal cells. Four weeks after NTP exposure, the total surface area consisting of endometriotic cysts was significantly smaller with less epithelial proliferative activity than the helium-exposed control, whereas the number of endometriotic lesions had not changed. Therefore, NTP exposure may be useful to prevent the progression and recurrence of endometriosis.

DOI： 10.1080/10715762.2016.1211273

Special issue for the 7th Biennial Meeting of Society for Free Radical Research-Asia (SFRR-Asia 2015 Thailand). 査読有り国際共著国際誌

Ungsurungsie M, Surh YJ, Toyokuni S, Davies MJ

Free radical research 50 巻 ( 10 ) 頁： 1045 - 1046 2016年10月

Preliminary characterization of a murine model for 1-bromopropane neurotoxicity: Role of cytochrome P450. 査読有り国際誌

Zong C, Garner CE, Huang C, Zhang X, Zhang L, Chang J, Toyokuni S, Ito H, Kato M, Sakurai T, Ichihara S, Ichihara G

Toxicology letters 258 巻頁： 249 - 258 2016年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Toxicology Letters

Neurotoxicity of 1-bromopropane (1-BP) has been reported in both human cases and animal studies. To date, neurotoxicity of 1-BP has been induced in rats but not in mice due to the lethal hepatotoxicity of 1-BP. Oxidization by cytochromes P450 and conjugation with glutathione (GSH) are two critical metabolism pathways of 1-BP and play important roles in toxicity of 1-BP. The aim of the present study was to establish a murine model of 1-BP neurotoxicity, by reducing the hepatotoxicity of 1-BP with 1-aminobenzotriazole (1-ABT); a commonly used nonspecific P450s inhibitor. The results showed that subcutaneous or intraperitoneal injection of 1-ABT at 50 mg/kg body weight BID (100 mg/kg BW/day) for 3 days, inhibited about 92–96% of hepatic microsomal CYP2E1 activity, but only inhibited about 62–64% of CYP2E1 activity in brain microsomes. Mice treated with 1-ABT survived even after exposure to 1200 ppm 1-BP for 4 weeks and histopathological studies showed that treatment with 1-ABT protected mice from 1-BP-induced hepatic necrosis, hepatocyte degeneration, and hemorrhage. After 4-week exposure to 1-BP, the brain weight of 1-ABT(+)/1200 ppm 1-BP group was decreased significantly. In 1-ABT-treated groups, expression of hippocampal Ran protein and cerebral cortical GRP78 was dose-dependently increased by exposure to 1-BP. We conclude that the control of hepatic P450 activity allows the observation of effects of 1-BP on the murine brain at a higher concentration by reduction of hepatotoxicity. The study suggests that further experiments with liver-specific control of P450 activity using gene technology might provide better murine models for 1-bromopropane-induced neurotoxicity.

DOI： 10.1016/j.toxlet.2016.07.006

Biphasic effects of l-ascorbate on the tumoricidal activity of non-thermal plasma against malignant mesothelioma cells. 査読有り国際共著国際誌

Shi L, Wang Y, Ito F, Okazaki Y, Tanaka H, Mizuno M, Hori M, Richardson DR, Toyokuni S

Archives of biochemistry and biophysics 605 巻頁： 109 - 16 2016年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Archives of Biochemistry and Biophysics

Non-thermal plasma (NTP) is a recently developed technology that elicits a variety of biological effects. This includes cancer cell-specific cytotoxicity, which is mainly attributed to the regional generation of reactive oxygen species (ROS). We studied the effects of NTP on malignant mesothelioma (MM) and its modulation by L-ascorbate. L-ascorbate is a major water-soluble anti-oxidant in vivo, but its pro-oxidant activity in vitro has been well recognized. Thus, the effects of ascorbate on the efficacy of NTP is important to examine. NTP exposure dose-dependently killed MM cells, whereas MM cells tolerated 1 mM L-ascorbate. However, brief pre-treatment with a pharmacological dose (250–750 μM) of L-ascorbate immediately prior to NTP exposure significantly increased its cytotoxicity in a dose-dependent manner, which was inhibited by the iron chelator, deferoxamine. However, paradoxically, this potentiating effect of L-ascorbate was completely abolished by a prolonged 4 h pre-incubation with L-ascorbate (500 μM). MM cytotoxicity induced by NTP was associated with immediate oxidative stress evaluated by 2′,7′-dichlorodihydrofluorecein diacetate, which was followed by an increase in the expression of the autophagosome marker, LC3B-II. In conclusion, MM can be a target for NTP treatment and L-ascorbate can increase or decrease its efficacy depending on the length of the pre-incubation period.

DOI： 10.1016/j.abb.2016.05.016

Low-temperature plasma in biology and medicine 査読有り国際誌

Hori M.

Archives of Biochemistry and Biophysics 605 巻頁： 1 - 2 2016年9月

Antenatal Saireito (TJ-114) Can Improve Pulmonary Hypoplasia and Pulmonary Vascular Remodeling in Nitrofen-Induced Congenital Diaphragmatic Hernia. 査読有り

Hirako S, Tsuda H, Kotani T, Sumigama S, Mano Y, Nakano T, Imai K, Li H, Toyokuni S, Kikkawa F.

Phytother Res. 30 巻 ( 9 ) 頁： 1474-80 2016年9月

Urokinase-type plasminogen activator receptor promotes proliferation and invasion with reduced cisplatin sensitivity in malignant mesothelioma. 査読有り

Wang S, Jiang L, Han Y, Hwu Chew S, Ohara Y, Akatsuka S, Weng L, Kawaguchi K, Fukui T, Sekido Y, Yokoi K, Toyokuni S.

Oncotarget. 2016 Sep 2. 頁： 11829 2016年9月

Preliminary characterization of a murine model for 1-bromopropane neurotoxicity: Role of cytochrome P450. 査読有り

Zong C, Garner CE, Huang C, Zhang X, Zhang L, Chang J, Toyokuni S, Ito H, Kato M, Sakurai T, Ichihara S, Ichihara G.

Toxicol Lett. 258 巻頁： 249-58 2016年9月

Biphasic effects of l-ascorbate on the tumoricidal activity of non-thermal plasma against malignant mesothelioma cells. 査読有り

Shi L, Wang Y, Ito F, Okazaki Y, Tanaka H, Mizuno M, Hori M, Richardson DR, Toyokuni S.

Arch Biochem Biophys. 605 巻頁： 106-16 2016年9月

Antenatal Saireito (TJ-114) Can Improve Pulmonary Hypoplasia and Pulmonary Vascular Remodeling in Nitrofen-Induced Congenital Diaphragmatic Hernia. 査読有り国際誌

Hirako S, Tsuda H, Kotani T, Sumigama S, Mano Y, Nakano T, Imai K, Li H, Toyokuni S, Kikkawa F

Phytotherapy research : PTR 30 巻 ( 9 ) 頁： 1474 - 80 2016年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Phytotherapy Research

Congenital diaphragmatic hernia (CDH) can induce lung hypoplasia and pulmonary hypertension and is associated with high mortality. The purpose of this study is to examine the efficacy and safety of antenatal Saireito (TJ-114), a traditional Japanese herbal medicine, in a rat CDH model. Sprague-Dawley rats were exposed to an herbicide (nitrofen, 100 mg) on embryonic day 9 (E9) to induce CDH, and antenatal Saireito (2000 mg/kg/day) was orally administered from E10 to E20. On E21, fetuses were delivered. Antenatal Saireito significantly decreased the incidence of CDH (p < 0.01), increased lung volume (p < 0.01), improved alveolarization and pulmonary artery remodeling using histological analysis, and improved respiratory function using gasometric analysis (pH; p < 0.05, and PCO2; p < 0.01). In addition, antenatal Saireito significantly decreased endothelin-1 and endothelin receptor A expression in the pulmonary arteries. Taken together, our results demonstrated that antenatal Saireito can improve fetal pulmonary hypoplasia and pulmonary vascular remodeling and, as a result, can improve respiratory function in a rat CDH model. Copyright © 2016 John Wiley & Sons, Ltd.

DOI： 10.1002/ptr.5645

Molecular hydrogen suppresses activated Wnt/beta-catenin signaling 査読有り国際誌

Lin Yingni, Ohkawara Bisei, Ito Mikako, Misawa Nobuaki, Miyamoto Kentaro, Takegami Yasuhiko, Masuda Akio, Toyokuni Shinya, Ohno Kinji

SCIENTIFIC REPORTS 6 巻 ( 6 ) 頁： 31986 2016年8月

Contrasting intra- and extracellular distribution of catalytic ferrous iron in ovalbumin-induced peritonitis. 査読有り国際誌

Ito F, Nishiyama T, Shi L, Mori M, Hirayama T, Nagasawa H, Yasui H, Toyokuni S

Biochemical and biophysical research communications 476 巻 ( 4 ) 頁： 600 - 606 2016年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Biochemical and Biophysical Research Communications

Iron is an essential nutrient for every type of life on earth. However, excess iron is cytotoxic and can lead to an increased cancer risk in humans. Catalytic ferrous iron [Fe(II)] is an initiator of the Fenton reaction, which causes oxidative stress by generating hydroxyl radicals. Recently, it became possible to localize catalytic Fe(II) in situ with a turn-on fluorescent probe, RhoNox-1. Here, we screened each organ/cell of rats to globally evaluate the distribution of catalytic Fe(II) and found that eosinophils showed the highest abundance. In various cells, lysosomes were the major organelle, sharing ∼40–80% of RhoNox-1 fluorescence. We then used an ovalbumin-induced allergic peritonitis model to study the dynamics of catalytic Fe(II). Peritoneal lavage revealed that the total iron contents per cell were significantly decreased, whereas an increase in the number of inflammatory cells (macrophages, neutrophils, eosinophils and lymphocytes) resulted in an increased total iron content of the peritoneal inflammatory cells. Notably, macrophages, eosinophils and neutrophils exhibited significantly increased catalytic Fe(II) with increased DMT1 expression and decreased ferritin expression, though catalytic Fe(II) was significantly decreased in the peritoneal lavage fluid. In conclusion, catalytic Fe(II) in situ more directly reflects cellular activity and the accompanying pathology than total iron does.

DOI： 10.1016/j.bbrc.2016.06.003

Molecular hydrogen suppresses activated Wnt/β-catenin signaling. 査読有り

Lin Y, Ohkawara B, Ito M, Misawa N, Miyamoto K, Takegami Y, Masuda A, Toyokuni S, Ohno K.

Sci Rep. 25 巻 ( 6 ) 頁： 31986 2016年8月

Contrasting intra- and extracellular distribution of catalytic ferrous iron in ovalbumin-induced peritonitis. 査読有り

Ito F, Nishiyama T, Shi L, Mori M, Hirayama T, Nagasawa H, Yasui H, Toyokuni S.

Biochem Biophys Res Commun. 476 巻 ( 4 ) 頁： 600-6 2016年8月

Iron function and carcinogenesis 査読有り国際誌

Akatsuka S., Toyokuni S.

Nihon rinsho. Japanese journal of clinical medicine 74 巻 ( 7 ) 頁： 1168 - 1175 2016年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nihon rinsho. Japanese journal of clinical medicine

Though iron is an essential micronutrient for humans, the excess state is acknowledged to be associated with oncogenesis. For example, iron overload in the liver of the patients with hereditary hemocromatosis highly increases the risk of hepatocellular carcinoma. Also, as to asbestos-related mesothelioma, such kinds of asbestos with a higher iron content are considered to be more carcinogenic. Iron is a useful element, which enables fundamental functions for life such as oxygen carrying and electron transport. However, in the situation where organisms are unable to have good control of it, iron turns into a dangerous element which catalyzes generation of reactive oxygen. In this review, I first outline the relationships between iron and cancer in general, then give an explanation about iron-related animal carcinogenesis models.

Scopus

The emerging role of progesterone receptor membrane component 1 (PGRMC1) in cancer biology. 査読有り

Cahill MA, Jazayeri JA, Catalano SM, Toyokuni S, Kovacevic Z, Richardson DR.

Biochim Biophys Acta. 2016 Jul 22. pii: S0304-419X 巻 ( 16 ) 頁： 30049-X. 2016年7月

Dual preventive benefits of iron elimination by desferal in asbestos-induced mesothelial carcinogenesis 査読有り国際誌

Jiang Li, Chew Shan-Hwu, Nakamura Kosuke, Ohara Yuuki, Akatsuka Shinya, Toyokuni Shinya

CANCER SCIENCE 107 巻 ( 7 ) 頁： 908 - 915 2016年7月

Possible therapeutic option of aqueous plasma for refractory ovarian cancer 査読有り国際誌

Kajiyama Hiroaki, Utsumi Fumi, Nakamura Kae, Tanaka Hiromasa, Mizuno Masaaki, Toyokuni Shinya, Hori Masaru, Kikkawa Fumitaka

CLINICAL PLASMA MEDICINE 4 巻 ( 1 ) 頁： 14 - 18 2016年7月

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論文 - 豊國　伸哉