Lansoprazole identified as a prophylactic agent for oxaliplatin-induced peripheral neuropathy using integrated in silico, in vitro, and in vivo analyses

Kobayashi, Akihide; Ikemura, Kenji; Ueno, Manami; Wakai, Eri; Yamane, Fumihiro; Okuda, Masahiro

doi:https://doi.org/10.1016/j.biopha.2025.118272

Lansoprazole identified as a prophylactic agent for oxaliplatin-induced peripheral neuropathy using integrated in silico, in vitro, and in vivo analyses

Kobayashi, Akihide; Ikemura, Kenji; Ueno, Manami et al.

Biomedicine and Pharmacotherapy, 2025, 189, 118272

アクセス数:126件（2026-02-16 12:11 集計）

固定URL: https://hdl.handle.net/11094/102905

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タイトル	Lansoprazole identified as a prophylactic agent for oxaliplatin-induced peripheral neuropathy using integrated in silico, in vitro, and in vivo analyses
著者	ORCID 0009-0005-2118-5280 0009-0005-2118-5280 Scopus Author ID 58746490300 58746490300 著者名 Kobayashi, Akihide
	NRID 1000070513935 1000070513935 ORCID 0000-0003-1870-9571 0000-0003-1870-9571 researchmap permalink Kenji_Ikemura Kenji_Ikemura Scopus Author ID 36783115100 36783115100 著者名 Ikemura, Kenji
	著者名 Ueno, Manami
	NRID 1000040964896 1000040964896 著者名 Wakai, Eri
	著者名 Yamane, Fumihiro
	NRID 1000070252426 1000070252426 researchmap permalink read0042639 read0042639 Scopus Author ID 56856467300 56856467300 著者名 Okuda, Masahiro
キーワード等	Drug repositioning
	Lansoprazole
	Organic cation transporter 2
	Oxaliplatin-induced peripheral neuropathy
	Proton pump inhibitors
内容	Kobayashi A., Ikemura K., Ueno M., et al. Lansoprazole identified as a prophylactic agent for oxaliplatin-induced peripheral neuropathy using integrated in silico, in vitro, and in vivo analyses. Biomedicine and Pharmacotherapy 189, 118272 (2025); https://doi.org/10.1016/j.biopha.2025.118272.
抄録	Oxaliplatin (L-OHP) is a platinum-based anticancer drug used to treat various malignant tumors. However, L-OHP-induced peripheral neuropathy (OIPN) is a major clinical problem that often limits treatment. As OIPN occurs when L-OHP accumulates in the dorsal root ganglion (DRG) via organic cation transporter 2 (OCT2/SLC22A2), drugs with OCT2 inhibitory properties may serve as prophylactic agents for OIPN. This study aimed to explore the potential prophylactic agents for OIPN using integrated model with the quantitative structure–activity relationship screening for human organic cation transporter 2 (hOCT2) inhibitors and two real-world data analyses of the Food and Drug Administration Adverse Event Reporting System and Japanese Adverse Drug Event Report, and subsequently evaluate the protective effects of the identified drugs against OIPN. Our integrated model identified lansoprazole, a proton pump inhibitor, as a potential prophylactic agent. In vitro uptake study using hOCT2-expressing HEK293 cells demonstrated that lansoprazole significantly inhibited the hOCT2-mediated transport of L-OHP. In the OIPN mouse model, concomitant lansoprazole drastically suppressed mechanical allodynia and cold hypersensitivity after repeated L-OHP administration. Moreover, the concentration of L-OHP in the DRG was significantly decreased by the concomitant administration of lansoprazole. In primary cultured mouse DRG neurons, cotreatment with lansoprazole significantly inhibited L-OHP uptake and restored the L-OHP-induced decrease in neurite length. These findings suggest that the concomitant administration of lansoprazole ameliorates OIPN by inhibiting OCT2-mediated L-OHP uptake in the mouse DRG. Our findings provide important insights for the establishment of novel protective approaches against OIPN.
出版者	Elsevier Masson s.r.l.
収録物名	Biomedicine and Pharmacotherapy
巻(号)	189
ページ	118272
刊行年月	2025-06-16
言語	英語
ハンドルURL	https://hdl.handle.net/11094/102905
PISSN	07533322
eISSN	19506007
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1016/j.biopha.2025.118272
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Biomedicine and Pharmacotherapy. 2025, 189, p. 118272
DC.title	Lansoprazole identified as a prophylactic agent for oxaliplatin-induced peripheral neuropathy using integrated in silico, in vitro, and in vivo analyses
DC.creator	Kobayashi, Akihide
	Ikemura, Kenji
	Ueno, Manami
	Wakai, Eri
	Yamane, Fumihiro
	Okuda, Masahiro
DC.publisher	Elsevier Masson s.r.l.
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-06-16
DC.identifier	https://doi.org/10.1016/j.biopha.2025.118272
DC.subject	Drug repositioning
	Lansoprazole
	Organic cation transporter 2
	Oxaliplatin-induced peripheral neuropathy
	Proton pump inhibitors
DC.description	Kobayashi A., Ikemura K., Ueno M., et al. Lansoprazole identified as a prophylactic agent for oxaliplatin-induced peripheral neuropathy using integrated in silico, in vitro, and in vivo analyses. Biomedicine and Pharmacotherapy 189, 118272 (2025); https://doi.org/10.1016/j.biopha.2025.118272.
DCTERMS.abstract	Oxaliplatin (L-OHP) is a platinum-based anticancer drug used to treat various malignant tumors. However, L-OHP-induced peripheral neuropathy (OIPN) is a major clinical problem that often limits treatment. As OIPN occurs when L-OHP accumulates in the dorsal root ganglion (DRG) via organic cation transporter 2 (OCT2/SLC22A2), drugs with OCT2 inhibitory properties may serve as prophylactic agents for OIPN. This study aimed to explore the potential prophylactic agents for OIPN using integrated model with the quantitative structure–activity relationship screening for human organic cation transporter 2 (hOCT2) inhibitors and two real-world data analyses of the Food and Drug Administration Adverse Event Reporting System and Japanese Adverse Drug Event Report, and subsequently evaluate the protective effects of the identified drugs against OIPN. Our integrated model identified lansoprazole, a proton pump inhibitor, as a potential prophylactic agent. In vitro uptake study using hOCT2-expressing HEK293 cells demonstrated that lansoprazole significantly inhibited the hOCT2-mediated transport of L-OHP. In the OIPN mouse model, concomitant lansoprazole drastically suppressed mechanical allodynia and cold hypersensitivity after repeated L-OHP administration. Moreover, the concentration of L-OHP in the DRG was significantly decreased by the concomitant administration of lansoprazole. In primary cultured mouse DRG neurons, cotreatment with lansoprazole significantly inhibited L-OHP uptake and restored the L-OHP-induced decrease in neurite length. These findings suggest that the concomitant administration of lansoprazole ameliorates OIPN by inhibiting OCT2-mediated L-OHP uptake in the mouse DRG. Our findings provide important insights for the establishment of novel protective approaches against OIPN.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	102905
citation_title	Lansoprazole identified as a prophylactic agent for oxaliplatin-induced peripheral neuropathy using integrated in silico, in vitro, and in vivo analyses
citation_author	Kobayashi, Akihide
	Ikemura, Kenji
	Ueno, Manami
	Wakai, Eri
	Yamane, Fumihiro
	Okuda, Masahiro
citation_publisher	Elsevier Masson s.r.l.
citation_language	英語
citation_date	2025-06-16
citation_journal_title	Biomedicine and Pharmacotherapy
citation_volume	189
citation_firstpage	118272
citation_doi	https://doi.org/10.1016/j.biopha.2025.118272
citation_public_url	https://hdl.handle.net/11094/102905

Lansoprazole identified as a prophylactic agent for oxaliplatin-induced peripheral neuropathy using integrated in silico, in vitro, and in vivo analyses

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