{"created":"2023-06-19T11:44:08.666879+00:00","id":13961,"links":{},"metadata":{"_buckets":{"deposit":"a2ed8b37-435f-4d11-974b-fc69314e750a"},"_deposit":{"created_by":16,"id":"13961","owners":[16],"pid":{"revision_id":0,"type":"depid","value":"13961"},"status":"published"},"_oai":{"id":"oai:mie-u.repo.nii.ac.jp:00013961","sets":["334:608:618:1262"]},"author_link":[],"item_7_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-09-16","bibliographicIssueDateType":"Issued"}}]},"item_7_date_granted_59":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2020-09-16"}]},"item_7_degree_grantor_57":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"三重大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"14101","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_7_degree_name_56":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)"}]},"item_7_description_14":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_7_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Cisplatin is widely used for the treatment of multiple solid tumors. Cisplatin-induced nephrotoxicity is caused by renal accumulation of cisplatin via human organic cation transporter 2 (hOCT2). As lansoprazole (LPZ), a proton pump inhibitor (PPI), is known to inhibit hOCT2 activity, LPZ might ameliorate cisplatin-induced nephrotoxicity. Previous study showed that concomitant LPZ administration ameliorated nephrotoxicity in patients receiving cisplatin. However, the detailed mechanism remains to be clarified. In the present study, the drug-drug interaction between LPZ and cisplatin was examined using hOCT2-expressing cultured cells and rat renal slices. Moreover, we investigated the effect of LPZ on cisplatin-induced nephrotoxicity and pharmacokinetics of cisplatin in rats. In the uptake study, LPZ potently inhibited uptake of cisplatin in hOCT2-expressing cultured cells and rat renal slices. In vivo rat study showed that concomitant LPZ significantly ameliorated cisplatin-induced nephrotoxicity and reduced renal accumulation of platinum (Pt) up to approximately 60% of cisplatin alone at 72 h after cisplatin intraperitoneal administration. Furthermore, renal uptake of Pt at 3 min after intravenous cisplatin administration in rats with cisplatin and LPZ decreased to 78% of rats with cisplatin alone. In addition, there was no significant difference in plasma Pt concentration between rats treated with and without LPZ at 3 min after cisplatin intravenous administration. These findings suggested that concomitant LPZ ameliorated cisplatin-induced nephrotoxicity by inhibiting rOCT2-mediated cisplatin uptake in rats, thus decreasing cisplatin accumulation in the kidney. The present findings provided important information for the establishment of novel protective approaches to minimize cisplatin-induced nephrotoxicity.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_7_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"本文/Department of Clinical Pharmacy and Biopharmaceutics, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan","subitem_description_type":"Other"},{"subitem_description":"33p","subitem_description_type":"Other"}]},"item_7_dissertation_number_60":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲医学第2035号"}]},"item_7_publisher_30":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"三重大学"}]},"item_7_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1002/bdd.2242","subitem_relation_type_select":"DOI"}}]},"item_7_text_31":{"attribute_name":"出版者（ヨミ）","attribute_value_mlt":[{"subitem_text_value":"ミエダイガク"}]},"item_7_text_63":{"attribute_name":"ノート","attribute_value_mlt":[{"subitem_text_value":"Biopharm Drug Dispos . 2020 Jun;41(6):239-247に掲載"}]},"item_7_text_65":{"attribute_name":"資源タイプ（三重大）","attribute_value_mlt":[{"subitem_text_value":"Doctoral Dissertation / 博士論文"}]},"item_7_version_type_15":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Hiramatsu, Shun-ichi","creatorNameLang":"en"},{"creatorName":"ヒラマツ, シュンイチ","creatorNameLang":"ja-Kana"},{"creatorName":"平松, 駿一","creatorNameLang":"ja"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-01-05"}],"displaytype":"detail","filename":"2020DM0914.pdf","filesize":[{"value":"547.4 kB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"2020DM0914","objectType":"fulltext","url":"https://mie-u.repo.nii.ac.jp/record/13961/files/2020DM0914.pdf"},"version_id":"5497f18f-7e26-4cec-89c2-d029ad163db2"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"cisplatin","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"lansoprazole","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"nephrotoxicity","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"organic cation transporter 2","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Concomitant lansoprazole ameliorates cisplatin-induced nephrotoxicity by inhibiting renal organic cation transporter 2 in rats","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Concomitant lansoprazole ameliorates cisplatin-induced nephrotoxicity by inhibiting renal organic cation transporter 2 in rats","subitem_title_language":"en"}]},"item_type_id":"7","owner":"16","path":["1262"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-01-05"},"publish_date":"2021-01-05","publish_status":"0","recid":"13961","relation_version_is_last":true,"title":["Concomitant lansoprazole ameliorates cisplatin-induced nephrotoxicity by inhibiting renal organic cation transporter 2 in rats"],"weko_creator_id":"16","weko_shared_id":-1},"updated":"2023-10-25T04:18:53.119630+00:00"}