Research of promotion and Support Headquarters

Yasuhiro Maeda

  (前田 康博)

Profile Information

Affiliation
Center for Joint Research Facilities Support, Fujita Health University
Degree
名古屋市立大学薬学研究科/博士(薬学)

J-GLOBAL ID
200901056880693640
researchmap Member ID
1000195297

External link

Papers

 60
  • Tomoya Kataoka, Hiroto Ito, Taiki Mori, Yuji Hotta, Akimasa Sanagawa, Yasuhiro Maeda, Yoko Furukawa-Hibi, Kazunori Kimura
    International journal of impotence research, Oct 30, 2022  
    We previously showed that castration of rats reduced erectile function over time; when testosterone replacement therapy was started 4 weeks after castration, erectile function improved. In this study, we examined the mechanism of improvement in erectile function following testosterone replacement therapy in rats. Thirty 12-week-old rats were divided into castrated (Cast), castrated with subcutaneous administration of testosterone (Cast + T), and sham (Sham) groups. Erectile function and mRNA and protein expression were evaluated in the rats by using standard methods. To assess erectile function, we measured the intracavernosal pressure, mean arterial pressure, mRNA expression of endothelial growth factors, and protein expression of endothelial nitric oxide synthase (eNOS). The intracavernosal pressure/mean arterial pressure ratio was significantly lower in the Cast group, and testosterone administration significantly improved (P = 0.017). Compared to the Cast group, the Cast+T group exhibited significantly increased mRNA expressions of vascular endothelial growth factor A (VEGF-A), intercellular adhesion molecule 1 (ICAM-1), transforming growth factor-β (TGF-β), nerve growth factor (NGF), α-smooth muscle actin (α-SMA), caveolae associated protein 1 (Cavin-1), Cavin-2, Cavin-3, sirtuin 1 (Sirt-1), sphingosine-1-phosphate 1 (S1P1), S1P2, and S1P3 and eNOS protein expression. Testosterone replacement therapy improved erectile function in castrated rats by increasing growth factors and eNOS protein.
  • 前田 康博, 中島 葉子, 横井 克幸, 伊藤 哲哉
    日本先天代謝異常学会雑誌, 38 184-184, Oct, 2022  
  • Tomoya Kataoka, Ayako Fukamoto, Yuji Hotta, Akimasa Sanagawa, Yasuhiro Maeda, Yoko Furukawa-Hibi, Kazunori Kimura
    Sexual medicine, 10(5) 100550-100550, Aug 5, 2022  
    BACKGROUND: Testosterone is an important hormone for the physical and mental health of men; however testosterone administration has also been suggested to adversely affect the cardiovascular system. AIM: To investigate the effects of excessive testosterone administration on vascular endothelial and erectile function in rats. METHODS: A total of seventy-five 12-week-old rats were divided into the following groups: Sham, castrated (Cast), castrated with subcutaneous administration of 100 mg/kg/month testosterone (Cast + T1), and castrated with subcutaneous administration of 100 mg/kg/week testosterone (Cast + T4). To observe the changes in testosterone level after the administration, rats were further divided into the following groups: control; T(6.25), wherein the rats were subcutaneously injected with 6.25 mg/kg testosterone; T(25) per week, wherein the rats were subcutaneously injected with 25 mg/kg testosterone per week; and T(100), wherein the rats were subcutaneously injected with 100 mg/kg testosterone per week. The relaxation responses of aorta were measured in these rats using standardized methods, and their erectile function was also evaluated. Statistical analysis of the obtained data was performed using two-way analysis of variance (ANOVA), Tukey-Kramer's multiple comparison test, or Student's t-test. OUTCOMES: At the end of the study period, endothelial function was evaluated through measurement of isometric tension, while erectile function was assessed using intracavernosal pressure (ICP), mean arterial pressure (MAP), and the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), sirtuin 1 (Sirt1) and vascular endothelial growth factor A. RESULTS: The ICP/MAP ratio in the Cast group (0.42 ± 0.04) was significantly lower than that in the Sham group (0.79 ± 0.07). The ICP/MAP ratio in the Cast + T1 group (0.73 ± 0.06) was significantly higher than that in the Cast group (P < .01) and that of the Cast + T4 (0.38 ± 0.01) group was unchanged (P > .05). The T(25) and T(100) groups exhibited significantly lower responses to ACh than the control group at 4 weeks (P < .01). Meanwhile, the ICP/MAP ratios in the T(25) group (0.44 ± 0.07) and T(100) group (0.47 ± 0.03) were significantly lower than that in the control group (0.67 ± 0.05) at stimulation frequencies of 16 Hz (P < .05). The expression of androgen receptor, Sirt1, and eNOS were significantly lower while that of iNOS was higher in the T(25) group compared with the control group (P < .05). CLINICAL TRANSLATION: The results based on this animal model indicate that extremely high testosterone levels may affect endothelial and erectile function. STRENGTHS AND LIMITATIONS: We found that high-dose testosterone administration decreased endothelial function in aorta and erectile function in rats. A major limitation of this study is that the blood concentration may not be representative of that in humans, and further research is needed. CONCLUSION: The findings suggest that high doses of testosterone may cause endothelial dysfunction in the aorta and erectile dysfunction in rats and that the blood concentration should be monitored after testosterone administration. Kataoka T, Fukamoto A, Hotta Y, et al. Effect of High Testosterone Levels on Endothelial Function in Aorta and Erectile Function in Rats. Sex Med 2022;XX:XXXXXX.
  • Tomoya Kataoka, Yuto Kawaki, Yohei Kito, Jun Suzuki, Taiki Mori, Yuji Hotta, Akimasa Sanagawa, Yoshihiro Kawade, Yasuhiro Maeda, Yoko Furukawa-Hibi, Kazunori Kimura
    Sexual medicine, 10(2) 100484-100484, Apr, 2022  
    BACKGROUND: A platinum-containing anti-cancer agent, oxaliplatin (L-OHP), is known to induce peripheral neuropathy, including erectile dysfunction (ED) as a side effect, while Gosha-jinki-gan (GJG) is a traditional Japanese herbal medicine mainly used for peripheral neuropathy. AIM: To investigate the effect of GJG on L-OHP-induced ED in rats. METHODS: Twelve-week-old male Wister/ST rats were categorized into the following groups: Sham, Sham+GJG, L-OHP, and L-OHP+GJG (each n = 10). The L-OHP and L-OHP+GJG groups were injected intravenously with L-OHP (4 mg/kg) for 2 consecutive days in the first week. Statistical significance was determined using Bonferroni's multiple comparison test. OUTCOMES: At the end of the study period, erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP) after cavernous nerve stimulation. Western blot analysis was used to assess the neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) levels, and quantitative polymerase chain reaction was used to assess the expression of phosphodiesterase-5 (PDE-5) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1. RESULTS: The ICP/MAP ratio of L-OHP rats (0.34 ± 0.06) was significantly lower than that of Sham rats (0.67 ± 0.03, P < .01), however, the ICP/MAP ratio of L-OHP+GJG rats (0.55 ± 0.01) was significantly higher than that of L-OHP rats (P < .01). There were no significant differences in the nNOS and eNOS protein expression between both groups (P > .05). GJG administration significantly decreased PDE-5 and NADPH oxidase-1 messenger RNA expressions in the L-OHP+GJG group. CLINICAL TRANSLATION: This animal model study suggests that GJG might be effective for erectile function in cancer survivors. STRENGTHS & LIMITATIONS: Our study identified that GJG had no notable side effects in the treated group. Further investigation of the cavernous nerve would also help elucidate the mechanism of GJG effect, which is a limitation of this study. CONCLUSION: We found that GJG administration improved L-OHP-induced ED by improving transcriptional PDE-5 expression. Kataoka T, Kawaki Y, Kito Y, et al. Gosha-Jinki-Gan Improved Erectile Dysfunction Caused by Anti-Cancer Agent Oxaliplatin by Decreasing Transcriptional Expression of Phosphodiesterase-5 in Rats. Sex Med 2022;10:100484.
  • Tomoya Kataoka, Junya Hidaka, Jun Suzuki, Taiki Mori, Daigaku Nakamura, Yuji Hotta, Akimasa Sanagawa, Yasuhiro Maeda, Yoko Furukawa-Hibi, Kazunori Kimura
    Sexual Medicine, 10(2) 100500-100500, Apr, 2022  

Misc.

 63
  • 中島 葉子, 前田 康博, 伊藤 哲哉
    臨床薬理の進歩, (40) 131-139, Jun, 2019  
    dihydropyrimidine dehydrogenase(DPD)欠損症患者のスクリーニング法として、肝臓におけるDPD活性と相関があるヒト末梢血リンパ球中DPDを用い、酵素反応後の生成物をUPLC-MS/MSで定量する方法について検討した。確立した定量法により、健常人9名と5-Fluorouracil(5-FU)投与患者17名のDPD活性を測定した。健常人のリンパ球を利用した酵素反応では、DHT生成量(平均値±標準偏差)は13.5±2.5pmol/4h/μg proteinであり、範囲は9.3〜15.7pmol/4h/μg proteinであった。重篤な副作用を呈しなかった5-FU投与患者群では、DHT生成量は7.2〜17.0pmol/4h/μg proteinとなり、DPD活性は正常平均値の53.3〜126.2%であった。健常人平均値の-2SD(8.5pmol/4h/μg protein)以下であった患者が2名存在したが、重篤な副作用は認めなかった。TS-1内服後にGrade 4以上の副作用を認めた1例では、DHT生成量は1.9pmol/4h/μg proteinで、DPD酵素活性が正常平均値の14.4%と有意に(Student&#039;s t検定、P&lt;0.001)低値であった。DPD活性が50%程度であれば、5-FUの投与による重篤な副作用は発現しないと考えるが、症例数が少ないため活性と副作用発現の関連の評価には、引き続き患者データを集める必要がある。本研究で確立した患者リンパ球を用いたDPD活性測定は、5-FU投与前スクリーニングとして有用であり、さらに遺伝子検査によるDPYD多型解析とDPD活性測定を組み合わせることで、日本人における5-FU副作用発現をきたすDPYD遺伝子多型の基盤作りにつながると考えられた。
  • 中島 葉子, 横井 克幸, 前田 康博, 吉川 哲史, 伊藤 哲哉
    日本先天代謝異常学会雑誌, 34 167-167, Sep, 2018  
  • 三宅 玲香, 前田 康博, 中島 葉子, 伊藤 哲哉, 後藤 佳奈, 堀田 祐志, 片岡 智哉, 木村 和哲
    日本先天代謝異常学会雑誌, 34 211-211, Sep, 2018  
  • 村瀬 美和, 前田 康博, 中島 葉子, 伊藤 哲哉, 堀田 祐志, 片岡 智哉, 木村 和哲
    JSBMS Letters, 43(Suppl.) 140-140, Aug, 2018  
  • 前田 康博, 後藤 佳奈, 中島 葉子, 但馬 剛, 堀田 祐志, 片岡 智哉, 木村 和哲, 伊藤 哲哉
    日本先天代謝異常学会雑誌, 33 202-202, Sep, 2017  

Research Projects

 10

Other

 1
  • Apr, 2006 - Present
    タンデム質量分析計によるメタボローム解析(先天代謝異常症における代謝物、酵素活性測定系。その他一般的一次代謝物の測定。Maeda et al. Brain & development ,2019)