Faculty of Agriculture Department of Veterinary Science


Associate Professor

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Degree 【 display / non-display

  • 博士(獣医学) ( 2010.3   山口大学 )

Research Areas 【 display / non-display

  • Life Science / Veterinary medical science


Papers 【 display / non-display

  • Blueberry Stem Extract Prevents Lacrimal Hyposecretion in Non-obese Diabetic Mice via Activation of AMPK

    Ogawa K., Ohno Y., Tagashira A., Urata K., Satoh K., Fujimoto N., Sonoda H., Ikeda M., Matsuzaki T., Nishiyama K., Kunitake H., Goto Y., Yamasaki M.

    In Vivo   37 ( 3 )   1003 - 1015   2023.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:In Vivo  

    Background/Aim: Tears secreted from the lacrimal gland are essential for preserving the ocular surface. Thus, dysfunction of the lacrimal gland in Sjögren’s syndrome (SS) can lead to dry eye, resulting in a reduced quality of life. We previously reported that blueberry ‘leaf’ water extract prevents lacrimal hyposecretion in male non-obese diabetic (NOD) mice in a SS-like model. In this study, we investigated the effect of blueberry ‘stem’ water extract (BStEx) on lacrimal hyposecretion in NOD mice. Materials and Methods: Male NOD mice were fed 1% BStEx or control (AIN-93G) for 2, 4, or 6 weeks from 4 weeks of age. Pilocarpine-induced tear secretion was measured using a phenol red-impregnated thread. The lacrimal glands were histologically evaluated by HE staining. Inflammatory cytokine levels in the lacrimal glands were measured using ELISA. Immunostaining was performed to examine aquaporin 5 (AQP5) localization. The expression levels of autophagy-related proteins, AQP5, and phosphorylated AMPK were measured using western blotting. Results: After feeding BStEx to mice for 4 or 6 weeks, tear volume was observed to have increased in the BStEx group compared with that in the control group. There were no significant differences in inflammatory cell infiltration, autophagy-related protein expression, or the localization and expression of AQP5 in the lacrimal glands between the two groups. In contrast, AMPK phosphorylation increased in the BStEx group. Conclusion: BStEx prevented lacrimal hyposecretion in the SS-like model of male NOD mice, probably by opening tight junctions via the activation of AMPK in lacrimal acinar cells.

    DOI: 10.21873/INVIVO.13174



  • Rhabdomyolysis, myoglobinuric nephrosis, and crystalline nephropathy in a captive bottlenose dolphin. Reviewed

    Nueangphuet P, Hamano T, Hirai T, Sakaguchi Y, Sonoda H, Otsuka M, Yamato O, Hobo S, Ikeda M, Yamaguchi R

    Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc   34 ( 4 )   668 - 673   2022.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Veterinary Diagnostic Investigation  

    A 5-y-old female bottlenose dolphin (Tursiops truncatus) from an aquarium in Japan had clinical signs of anorexia, vomiting, and bradykinesia. Enrofloxacin and lactated Ringer solution were administered for treatment of bacterial infection and for rehydration. Elevations of creatine kinase and aspartate aminotransferase activities were detected on day 4 of treatment, indicating that rhabdomyolysis had developed on day 3. On day 5, serum creatinine and urea concentrations increased and remained high throughout the remaining treatment; the dolphin died on day 16. Postmortem examination revealed massive necrosis of the longissimus dorsi muscles. Histologic examination revealed extensive necrosis of skeletal myofibers, multifocal renal tubular necrosis with intratubular casts and crystals, and suppurative bronchopneumonia. The renal casts labeled positively with anti-myoglobin antibody; expression of aquaporin-1 was decreased in renal tubules compared to normal kidney tissue. To our knowledge, this description of clinicopathologic findings of rhabdomyolysis leading to acute kidney injury with concomitant crystalline nephropathy has not been reported previously in a bottlenose dolphin.

    DOI: 10.1177/10406387221090516



  • Upregulation of NADPH Oxidase 2 Contributes to Renal Fibrosis in pcy Mice: An Experimental Model of Nephronophthisis Reviewed

    Hoshino Y., Sonoda H., Mikoda N., Ikeda M.

    Nephron   1 - 11   2021.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Nephron  

    Background: DBA/2FG-pcy (pcy) mice harbor a homozygous Nphp3 missense mutation and develop nephronophthisis with renal interstitial fibrosis. Previous studies have shown that aberrant oxygen homeostasis contributes to the renal pathology in pcy mice, but the underlying molecular mechanism remains largely unknown. Methods: pcy mice and a control strain, DBA/2N (DBA) mice, were used. Renal levels of 62 mRNAs involved in oxygen homeostasis were investigated by real-Time PCR, and the resulting data were used for extraction of pathological pathways. On the basis of the genes found to be upregulated and pathway analysis, further studies were performed using immunoblotting, immunohistochemistry, and pharmacological intervention. Results: In comparison with DBA mice, the levels of 18 mRNAs were altered by >2-fold in pcy mice. Pathway analysis extracted molecular pathways related to oxidative stress, inflammation, and cell adhesion. As the levels of mRNAs relevant to the NADPH oxidase 2 (NOX2) pathway were prominently (4 genes >5-fold) increased in pcy mice, we further analyzed the molecules related to this pathway. A time course study suggested that the pathway was gradually activated in pcy mice from at least 5 weeks of age. Immunohistochemistry study revealed that NOX2 protein was colocalized with a macrophage marker protein in the renal interstitium. Moreover, treatment of pcy mice with apocynin, an inhibitor of the NOX2 pathway, ameliorated the renal fibrosis. Conclusion: Our findings suggest that the activation of the NOX2 pathway, possibly mediated by macrophage infiltration, plays a pivotal role in progressive renal fibrosis in pcy mice.

    DOI: 10.1159/000520697



  • Reduced urinary release of AQP1- and AQP2-bearing extracellular vesicles in patients with advanced chronic kidney disease Reviewed

    Oshikawa-Hori S., Yokota-Ikeda N., Sonoda H., Sasaki Y., Ikeda M.

    Physiological Reports   9 ( 17 )   e15005   2021.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Physiological Reports  

    Although several studies have shown that release of water channel proteins, aquaporin 1 (AQP1) and AQP2 in urinary extracellular vesicles (uEV-AQP1 and -AQP2), were altered in experimental kidney injury models, their release in human chronic kidney disease (CKD) has been largely unexplored. The aim of the present study was to clarify whether the release of uEV-AQP1 and -AQP2 is altered in patients with CKD. Urine samples were collected from 15 healthy volunteers (normal group) and 62 CKD patients who were categorized into six glomerular filtration rate (GFR) categories (G1, G2, G3a, G3b, G4, and G5) in between 2005 and 2016 at Miyazaki Prefectural Miyazaki Hospital, Japan. uEV-proteins were evaluated by immunoblot analysis. The release of AQP1 and AQP2 were significantly decreased in patients with both CKD G4 and G5, in comparison with the normal group. The area under the receiver operating characteristic (ROC) curve (AUC) values for AQP1 and AQP2 in patients with CKD G4 and G5 were 0.926 and 0.881, respectively. On the other hand, the AUC values in patients with CKD G1-G3 were 0.512 for AQP1 and 0.680 for AQP2. Multiple logistic regression analysis showed that AQP1 and AQP2 in combination were useful for detecting CKD G4 and G5, with a higher AUC value of 0.945. These results suggest that the release of uEV-AQP1 and -AQP2 was decreased in patients with CKD G4 and G5, and these proteins might be helpful to detect advanced CKD.

    DOI: 10.14814/phy2.15005



  • Onion (Allium cepa l.)-derived nanoparticles inhibited lps-induced nitrate production, however, their intracellular incorporation by endocytosis was not involved in this effect on raw264 cells Reviewed

    Yamasaki M., Yamasaki Y., Furusho R., Kimura H., Kamei I., Sonoda H., Ikeda M., Oshima T., Ogawa K., Nishiyama K.

    Molecules   26 ( 9 )   2021.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Molecules  

    The aim of this study was to evaluate the involvement of nanoparticles prepared from Allium cepa L. as anti-inflammatory agents. In the present study, we identified nanoparticles from Allium cepa L. using the ultracentrifugation exosome purification method. The nanoparticles were referred to as 17,000× g and 200,000× g precipitates, and they contained quercetins, proteins, lipids, and small-sized RNA. The nanoparticles inhibited nitric oxide production from lipopolysaccharide (LPS)-stimulated RAW264 cells without cytotoxic properties. Cellular incorporation was confirmed by laser microscopic observation after PKH26 staining. The inhibition of caveolae-dependent endocy-tosis and macropinocytosis significantly prevented the incorporation of the nanoparticles but had no effect on the inhibition of nitric oxide in RAW264 cells. Collectively, the identified nanoparticles were capable of inhibiting the LPS response via extracellular mechanisms. Taken together, the way of consuming Allium cepa L. without collapsing the nanoparticles is expected to provide an efficient anti-inflammatory effect.

    DOI: 10.3390/molecules26092763



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Books 【 display / non-display

  • 薬理学・毒性学実験

    園田紘子、池田正浩( Role: Joint author ,  VI消化器・生殖器・泌尿器系に作用する薬物 37.腎臓に作用(利尿に影響する)薬物)

    文永堂出版  2023.3 

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    Language:Japanese Book type:Textbook, survey, introduction

  • Urinary Exosomes as a Possible Source of Kidney Disease Biomarkers International journal

    Abdeen A., Sonoda H., Tanaka A., Ikeda M.( Role: Joint author)

    Role of Exosomes in Biological Communication Systems  2020.1  ( ISBN:9789811565984

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    Language:English Book type:Textbook, survey, introduction

    Urinary exosomes, one of several types of extracellular vesicles, contain specific molecules involved in both renal function and disease. Therefore, in the field of nephrology, exosome research is expected to shed new light on physiological functions and lead to discovery of new diagnostic and therapeutic methods. In this chapter, we outline the application of molecules contained in urinary exosomes as biomarkers of renal disease.

    DOI: 10.1007/978-981-15-6599-1_10


  • 大・中・小動物実験プロトコール

    池田正浩、園田紘子( Role: Joint author)

    宮日文化情報センター  2016.3 

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    Responsible for pages:80-82   Language:Japanese Book type:Scholarly book

MISC 【 display / non-display

  • 尿中細胞外小胞(エクソソーム)と腎疾患 Invited


    生体の科学   67 ( 5 )   406 - 407   2016.10

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:医学書院  

  • Aquaporins in urinary extracellular vesicles (exosomes).

    Oshikawa S, Sonoda H, Ikeda M

    International journal of molecular sciences   2016.6

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    Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:Molecular Diversity Preservation International Multidisciplinary Digital Publishing Institute  

    DOI: 10.3390/ijms17060957

  • 腎疾患におけるエクソソーム

    池田正浩, 園田紘子

    BIO Clinica   29 ( 6 )   30 - 33   2014.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:北隆館  

  • Sepsis/MOFとAKI

    園田紘子, 髙橋早樹, 池田正浩

    ICUとCCU(集中治療医学)   34 ( 4 )   283 - 289   2010.4

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:医学図書出版株式会社  

  • AKIと多臓器不全、敗血症

    園田紘子, 池田正浩, 池田直子

    臨床雑誌「内科」   102 ( 1 )   26 - 31   2008.7

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:南江堂  

Presentations 【 display / non-display

  • An estimation of urine flow rate using urinary creatinine excretion rate in rats


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    Event date: 2022.11.30 - 2022.12.3

    Language:English   Presentation type:Poster presentation  

  • 合成副腎皮質ホルモン製剤のラットにおける利尿作用に関する研究

    上間 圭人、園田 紘子、池田 正浩

    第75回日本薬理学会西南部会  2022.10.1 

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    Event date: 2022.10.1

    Language:Japanese   Presentation type:Oral presentation (general)  

  • デキサメタゾン投与による利尿メカニズムに関する研究

    森永 理央、園田 紘子、池田 正浩

    第165回日本獣医学会学術集会  2022.9.6 

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    Event date: 2022.9.6 - 2022.9.8

    Language:Japanese   Presentation type:Oral presentation (general)  

  • A candidate molecule for non-invasive biomarkers in renal Nrf2 activation

    Haruka Takayama, Ayae Tanaka, Hiroko Sonoda, Masahiro Ikeda

    第95回日本薬理学会年会  2022.3.9 

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    Event date: 2022.3.7 - 2022.3.9

    Language:English   Presentation type:Poster presentation  

  • 急性腎不全モデルマウスにおけるポリマー沈殿法で単離した血中細胞外小胞mRNAの解析


    第74回日本薬理学会西南部会  2021.11.20 

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    Event date: 2021.11.20

    Language:Japanese   Presentation type:Poster presentation  

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Awards 【 display / non-display

  • 第66回日本薬理学会西南部会優秀発表賞

    2013.11   日本薬理学会西南部会  


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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

Grant-in-Aid for Scientific Research 【 display / non-display

  • 分子時計によるアクアポリン1発現調節機構の解明と腎障害への関与についての研究

    Grant number:21K05922  2021.04 - 2024.03

    独立行政法人日本学術振興会  科学研究費補助金  基盤研究(C)


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    Authorship:Principal investigator 

  • 尿中exosome RNAsに着目した薬剤性腎障害診断マーカーの探索研究

    Grant number:15K18784   2015.04 - 2018.03

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator 

    腎疾患は医療および獣医領域において罹患率および死亡率の高い疾患で、有用な早期診断マーカーがないことが問題となっている。本研究では非侵襲的に得ることのできる尿にexosomeと呼ばれる小胞が含まれることに着目した。このexosomeには由来細胞のタンパク質やmRNA、miRNA(RNAs)が含まれており、これらはその由来細胞の状態を反映したバイオマーカーとなる可能性が考えられる。本研究はタンパク質よりも解析が簡便なRNAsに着目し、薬剤性腎障害ラットモデルを用いて尿中exosome RNAsの腎疾患バイオマーカーとしての有用性を検討することを目的として行う。

  • 尿中エクソソームアクアポリン1およびアクアポリン2排泄の生理的調節機構の基礎研究

    Grant number:24780287  2012.04 - 2015.03

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator