Search Results 1-20 of 93

  • 1 / 5
  • Imaging mass spectrometry for toxicity assessment: a useful technique to confirm drug distribution in histologically confirmed lesions

    Kashimura Akane , Tanaka Kouji , Sato Hiroko , Kaji Hidefumi , Tanaka Masaharu

    … To evaluate the usefulness of imaging mass spectrometry (IMS) technology for assessing drug toxicity, we analyzed animal tissues in an amiodarone (AMD)-induced phospholipidosis model by IMS and confirmed the relationship between the distribution of AMD, its metabolites, and representative phospholipids (phosphatidylcholine, PC) and histological changes. …

    Journal of Toxicologic Pathology 31(3), 221-227, 2018

    J-STAGE Ichushi Web

  • Imaging mass spectrometry for toxicity assessment: a useful technique to confirm drug distribution in histologically confirmed lesions

    KASHIMURA Akane , TANAKA Kouji , SATO Hiroko , KAJI Hidefumi , TANAKA Masaharu

    … <p>To evaluate the usefulness of imaging mass spectrometry (IMS) technology for assessing drug toxicity, we analyzed animal tissues in an amiodarone (AMD)-induced phospholipidosis model by IMS and confirmed the relationship between the distribution of AMD, its metabolites, and representative phospholipids (phosphatidylcholine, PC) and histological changes. …

    Journal of Toxicologic Pathology, 2018

    J-STAGE

  • Assessment of amiodarone-induced phospholipidosis using chimeric mice with humanized liver  [in Japanese]

    SANOH Seigo , YAMACHIKA Yuto , TAMURA Yuka , YOSHIZANE Yasumi , ISHIDA Yuji , TATENO Chise , OHTA Shigeru

    【目的】医薬品候補化合物の実験動物における毒性からヒトにおける毒性を予測するには、その感受性や関与する薬物代謝の種差を考慮する必要がある。マウス肝臓がヒト肝細胞で置換される「ヒト肝細胞キメラマウス」は、肝臓で惹起する医薬品毒性や薬物代謝の予測評価に有用なモデル動物として期待されている。医薬品開発の中止要因のひとつとして毒性試験の所見となる薬剤誘発性リン脂質症が挙げられる。本研究では、検証化合物とし …

    Annual Meeting of the Japanese Society of Toxicology 44.1(0), P-248, 2017

    J-STAGE

  • Evaluation of di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (22:6 BMP) as biomarker of drug-induced phospholipidosis in a 10-day repeated oral dose study of amiodarone in rats  [in Japanese]

    MIYAKE Manami , FUJITA Takuya , KOIKE Tomohiro , KUWATA Kazunori , NISHIKAWA Satomi , INOUE Yoshimi , TATEOKA Takashi , SHIMIZU Toshinobu

    【目的】薬剤誘発性リン脂質症(DIPL)は,カチオン性両親媒性薬剤により各種組織にリン脂質が異常蓄積する事で惹起され,大量のリン脂質蓄積は重篤な臓器不全を引き起こす事がある.リン脂質症の確定診断には,電子顕微鏡下でラメラ構造の確認が必要であり,利便性の高い非侵襲的マーカーが求められてきた.DIPL新規バイオマーカーとして注目される22:6 bis(monoacylglycerol)phosphat …

    Annual Meeting of the Japanese Society of Toxicology 44.1(0), P-16, 2017

    J-STAGE

  • Investigation of the utility of HepaRG cells for predicting phospholipidosis  [in Japanese]

    TOMIDA Takafumi , ISHIMURA Masakazu , KONNO Yoshihiro

    … 【目的】リン脂質症(Phospholipidosis: PLD)は、リン脂質が肝臓、腎臓及び肺等の様々な細胞質内に蓄積することを特徴とし、カチオン性両親媒性構造を有する多くの化合物によって引き起こされることが知られている。 …

    Annual Meeting of the Japanese Society of Toxicology 44.1(0), P-154, 2017

    J-STAGE

  • Assessment of amiodarone-induced phospholipidosis in chimeric mice with a humanized liver

    Sanoh Seigo , Yamachika Yuto , Tamura Yuka , Kotake Yaichiro , Yoshizane Yasumi , Ishida Yuji , Tateno Chise , Ohta Shigeru

    … Drug-induced phospholipidosis (DIPL), in which phospholipids accumulate, is a known entity. … Changes in various phosphatidylcholine (PhC) molecules were investigated in the liver of chimeric mice after administering amiodarone, which induces phospholipidosis. …

    The Journal of Toxicological Sciences 42(5), 589-596, 2017

    J-STAGE Ichushi Web

  • A cell-based assay using HepaRG cells for predicting drug-induced phospholipidosis

    Tomida Takafumi , Ishimura Masakazu , Iwaki Masahiro

    … cell-based assay system for predicting drug-induced phospholipidosis (PLD) was investigated. …

    The Journal of Toxicological Sciences 42(5), 641-650, 2017

    J-STAGE Ichushi Web

  • Characteristics of corneal phospholipidosis induced by topical ocular application of chloroquine and amiodarone in rabbits

    Yamagiwa Yoshinori , Haranosono Yu , Nemoto Shingo , Atsumi Ikuyo , Kurata Masaaki , Kito Gakushi , Hatakeyama Hirofumi , Koizumi Haruko , Sakaki Hideyuki

    … Several cationic-amphiphilic drugs such as chloroquine and amiodarone are known to induce phospholipidosis in the cornea by systemic administration. … However, the characteristics of ophthalmological and pathological changes when phospholipidosis-inducing drugs are topically applied have not been well studied. …

    Journal of Toxicologic Pathology 30(2), 135-143, 2017

    J-STAGE Ichushi Web

  • Plasma lipid profiling of rats with tamoxifen-induced steatosis and/or phospholipidosis  [in Japanese]

    SAITO Kosuke , MAEKAWA Kyoko , SAITO Yoshiro , GODA Keisuke , YAMADA Naohito , KOBAYASHI Akio , TAKAHASHI Tadakazu , MATSUI Takuya , SHODA Toshiyuki , KUNO Hideyuki , SUGAI Shoichiro

    臨床において乳癌治療薬として広く用いられている非ステロイド性の抗エストロゲン薬タモキシフェンは、臨床及び非臨床試験で脂肪肝あるいはリン脂質症を引き起こすことが知られている。また、非臨床における脂肪肝は、臨床で肝障害として検出されるケースも散見され、非臨床におけるリン脂質症は開発中止となっている。そこで我々は、タモキシフェンを投与したラットの血漿を用いた脂質メタボロミクスを行い、バイオマーカー探索を …

    Annual Meeting of the Japanese Society of Toxicology 43.1(0), P-40, 2016

    J-STAGE

  • A Novel Biomarker for Cellular Toxicity and Phospholipid Accumulation by Cationic Amphiphilic Drugs

    HAMAGUCHI Ryohei , KURODA Yukihiro

    … Drug-induced phospholipidosis (DIPL) is a phospholipid-hyperaccumulated state in cells, tissues and organs after treatment with cationic amphiphilic drugs (CADs). … The biological meaning of phospholipidosis remains unknown. …

    CHROMATOGRAPHY 37(1), 35-38, 2016

    J-STAGE

  • Establishment of an <i>in silico</i> phospholipidosis prediction method using descriptors related to molecular interactions causing phospholipid–compound complex formation

    Haranosono Yu , Nemoto Shingo , Kurata Masaaki , Sakaki Hideyuki

    … Although phospholipidosis (PLD) often affects drug development, there is no convenient <i>in vitro</i> …

    The Journal of Toxicological Sciences 41(2), 321-328, 2016

    J-STAGE Ichushi Web

  • Detection of metabolic activation leading to drug-induced phospholipidosis in rat hepatocyte spheroids

    Takagi Masashi , Sanoh Seigo , Santoh Masataka , Ejiri Yoko , Kotake Yaichiro , Ohta Shigeru

    … Drug-induced phospholipidosis (PLD) is one of the adverse reactions to treatment with cationic amphiphilic drugs. …

    The Journal of Toxicological Sciences 41(1), 155-164, 2016

    J-STAGE Ichushi Web

  • Drug-Induced Phospholipidosis Assessment from Nonclinical to Clinical Studies (トランスレーショナルリサーチ)

    Hsieh Frank , Tengstrand Elizabeth

    谷本学校毒性質問箱 (17), 24-37, 2015

  • Evaluation of phospholipidosis considering drug metabolism in rat hepatocyte three-dimensional culture  [in Japanese]

    TAKAGI Masashi , SANOH Seigo , SANTOH Masataka , EJIRI Yoko , OHTA Sigeru

    【背景・目的】薬剤誘発性リン脂質症は、陽イオン性両親媒性構造を持つ多くの薬剤により誘起され、肝臓など様々な臓器へのリン脂質蓄積を特徴とする疾患である。近年、本疾患の評価系として物性を考慮した in silico 評価系や、培養細胞を用いた in vitro 評価系の構築が報告されている。しかし、これらの評価と in vivo 評価に乖離がみられる場合もある。この要因として生体内における代謝の寄与を …

    Annual Meeting of the Japanese Society of Toxicology 42.1(0), P-47, 2015

    J-STAGE

  • Developmentof in silico Phospholipidosis Prediction Method for Hydrophilic Compounds  [in Japanese]

    HARANOSONO Yu , YAMAGIWA Yoshinori , KURATA Masaaki , NEMOTO Shingo , ATSUMI Ikuyo , SAKAKI Hideyuki

    … リン脂質症(Phospholipidosis: PLD)は、カチオン性と両親媒性を有する薬剤(Cationic-Amphiphilic-Drugs, CADs)により誘導され、リン脂質あるいはリン脂質との複合体が細胞内に蓄積し全身では高脂血症、網膜障害などを引き起こすことが知られている。 …

    Annual Meeting of the Japanese Society of Toxicology 41.1(0), P-68, 2014

    J-STAGE

  • Phospholipid biomarker discovery for drug-induced phospholipidosis using cultured cells  [in Japanese]

    HAMAGUCHI Ryohei , TANIMOTO Toshiko , KURODA Yukihiro

    【目的】薬剤誘発性ホスホリピドーシスは,塩基性両親媒性薬物(CAD)の反復投与により惹起される副作用である.その確定診断は組織生検によるが,被験者の負担を考慮するとバイオマーカーの利用が望ましい.今回,我々はDIPLの新たなリン脂質バイオマーカーの探索を培養細胞レベルで実施した.<br>【実験】ウシ胎児血清,抗生物質を含むRPMI-1640培地で培養したRAW264細胞,THP-1細胞 …

    Annual Meeting of the Japanese Society of Toxicology 41.1(0), P-206, 2014

    J-STAGE

  • The utility of parameters from an in vitro assay in predicting drug-induced phospholipidosis risk: correlation with in vivo data  [in Japanese]

    KIYOKAWA Jumpei , AKAI Sho , HONDA Masaki , INOUE Tomoaki , TABO Mitsuyasu

    【目的】薬物誘発性リン脂質症(PLD)は,全身諸臓器でリン脂質の異常蓄積を示す毒性所見である。創薬研究におけるPLD回避策として,物理化学的パラメータや<i>in vitro</i>アッセイでの評価が広く用いられているが,従来の解析手法によるポテンシャル評価は,必ずしも<i>in vivo</i>(動物試験)におけるPLDの発現を反映しておらず,その …

    Annual Meeting of the Japanese Society of Toxicology 41.1(0), P-207, 2014

    J-STAGE

  • Phospholipidosis: Histologic finding or histopathology?  [in Japanese]

    HASTINGS Kenneth L.

    … Characterized by intracellular inclusions called lamellar bodies, phospholipidosis is also a common finding in nonclinical toxicology studies designed to enable clinical trials and marketing applications for new drugs. … Phospholipidosis is a finding usually associated with what are generally referred to as cationic amphiphilic drugs (CADS). …

    Annual Meeting of the Japanese Society of Toxicology 41.1(0), EL6, 2014

    J-STAGE

  • Pathology and Neurotoxicity in Dogs after Repeat Dose Exposure to a Serotonin 5-HT<sub>1B</sub> Inhibitor

    Chang Jane C.F. , Ciaccio Paul , Schroeder Patricia , Wright Lindsay , Westwood Russell , Berg Anna-Lena

    … In the 1-month study, there were minimal neuronal vacuolation in the brain, a marked increase in liver enzymes accompanied by hepatocellular degeneration/necrosis and phospholipidosis (PLD), and PLD/cholecystitis in the gallbladder of animals dosed at 47 mg/kg/day. …

    Journal of Toxicologic Pathology 27(1), 31-42, 2014

    J-STAGE Ichushi Web

  • In vitro validation of drug-induced phospholipidosis

    PARK Sora , CHOI You-Jin , LEE Byung-Hoon

    … Intracellular accumulation of phospholipids with lamellar bodies is a hallmark of drug-induced phospholipidosis (PLD) which is caused by impaired phospholipid metabolism of the lysosome. …

    The Journal of Toxicological Sciences 37(2), 261-267, 2012-04-01

    J-STAGE Ichushi Web References (27)

  • 1 / 5
Page Top