Esomeprazole prevents oxaliplatin-induced peripheral neuropathy through inhibiting organic cation transporter 2 in mice

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

doi:https://doi.org/10.1016/j.ejps.2025.107309

Esomeprazole prevents oxaliplatin-induced peripheral neuropathy through inhibiting organic cation transporter 2 in mice

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

European Journal of Pharmaceutical Sciences, 2025, 214, 107309

アクセス数:35件（2026-02-15 23:51 集計）

固定URL: https://hdl.handle.net/11094/103664

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タイトル	Esomeprazole prevents oxaliplatin-induced peripheral neuropathy through inhibiting organic cation transporter 2 in mice
著者	著者名 Ueno, Manami
	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
	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	Esomeprazole
	Organic cation transporter 2
	Oxaliplatin-induced peripheral neuropathy
	Proton pump inhibitor
内容	Ueno M., Kobayashi A., Ikemura K., et al. Esomeprazole prevents oxaliplatin-induced peripheral neuropathy through inhibiting organic cation transporter 2 in mice. European Journal of Pharmaceutical Sciences 214, 107309 (2025); https://doi.org/10.1016/j.ejps.2025.107309.
抄録	Oxaliplatin (L-OHP) is widely used as a key drug for the treatment of various cancers, including colorectal cancer. However, L-OHP accumulates in the dorsal root ganglion (DRG) via organic cation transporter 2 (OCT2/SLC22A2), causing L-OHP-induced peripheral neuropathy (OIPN), a major clinical problem. Although proton pump inhibitors (PPIs) exhibit off-target OCT2 inhibitory effects, it remains unclear whether PPIs other than lansoprazole also inhibit OCT2-mediated L-OHP transport and prevent OIPN. This study aimed to investigate the inhibitory effects of PPIs on human OCT2 (hOCT2)-mediated L-OHP transport and assess their prophylactic effects against OIPN through in vitro and in vivo studies. Among the tested PPIs (lansoprazole, omeprazole, rabeprazole, and esomeprazole), the inhibitory effect of esomeprazole on hOCT2-mediated L-OHP transport was greater than those of other PPIs. In the OIPN mouse model, concomitant esomeprazole drastically ameliorated mechanical allodynia and cold hypersensitivity induced by L-OHP. Furthermore, concomitant esomeprazole administration significantly reduced L-OHP accumulation in the mouse DRG without affecting L-OHP plasma concentration. In primary cultures of mouse DRG neurons, cotreatment with esomeprazole significantly inhibited L-OHP uptake and completely restored L-OHP-induced neurite degeneration. Thus, to the best of our knowledge, our study demonstrates for the first time that concomitant esomeprazole prevents OIPN, at least in part, by inhibiting OCT2-mediated L-OHP transport into the DRG, thus decreasing L-OHP accumulation in the DRG. These findings provide important information for the establishment of novel protective approaches to minimize OIPN.
出版者	Elsevier B.V.
収録物名	European Journal of Pharmaceutical Sciences
巻(号)	214
ページ	107309
刊行年月	2025-10-08
言語	英語
ハンドルURL	https://hdl.handle.net/11094/103664
PISSN	09280987
eISSN	18790720
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1016/j.ejps.2025.107309
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	European Journal of Pharmaceutical Sciences. 2025, 214, p. 107309
DC.title	Esomeprazole prevents oxaliplatin-induced peripheral neuropathy through inhibiting organic cation transporter 2 in mice
DC.creator	Ueno, Manami
	Kobayashi, Akihide
	Ikemura, Kenji
	Wakai, Eri
	Yamane, Fumihiro
	Okuda, Masahiro
DC.publisher	Elsevier B.V.
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-10-08
DC.identifier	https://doi.org/10.1016/j.ejps.2025.107309
DC.subject	Esomeprazole
	Organic cation transporter 2
	Oxaliplatin-induced peripheral neuropathy
	Proton pump inhibitor
DC.description	Ueno M., Kobayashi A., Ikemura K., et al. Esomeprazole prevents oxaliplatin-induced peripheral neuropathy through inhibiting organic cation transporter 2 in mice. European Journal of Pharmaceutical Sciences 214, 107309 (2025); https://doi.org/10.1016/j.ejps.2025.107309.
DCTERMS.abstract	Oxaliplatin (L-OHP) is widely used as a key drug for the treatment of various cancers, including colorectal cancer. However, L-OHP accumulates in the dorsal root ganglion (DRG) via organic cation transporter 2 (OCT2/SLC22A2), causing L-OHP-induced peripheral neuropathy (OIPN), a major clinical problem. Although proton pump inhibitors (PPIs) exhibit off-target OCT2 inhibitory effects, it remains unclear whether PPIs other than lansoprazole also inhibit OCT2-mediated L-OHP transport and prevent OIPN. This study aimed to investigate the inhibitory effects of PPIs on human OCT2 (hOCT2)-mediated L-OHP transport and assess their prophylactic effects against OIPN through in vitro and in vivo studies. Among the tested PPIs (lansoprazole, omeprazole, rabeprazole, and esomeprazole), the inhibitory effect of esomeprazole on hOCT2-mediated L-OHP transport was greater than those of other PPIs. In the OIPN mouse model, concomitant esomeprazole drastically ameliorated mechanical allodynia and cold hypersensitivity induced by L-OHP. Furthermore, concomitant esomeprazole administration significantly reduced L-OHP accumulation in the mouse DRG without affecting L-OHP plasma concentration. In primary cultures of mouse DRG neurons, cotreatment with esomeprazole significantly inhibited L-OHP uptake and completely restored L-OHP-induced neurite degeneration. Thus, to the best of our knowledge, our study demonstrates for the first time that concomitant esomeprazole prevents OIPN, at least in part, by inhibiting OCT2-mediated L-OHP transport into the DRG, thus decreasing L-OHP accumulation in the DRG. These findings provide important information for the establishment of novel protective approaches to minimize OIPN.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	103664
citation_title	Esomeprazole prevents oxaliplatin-induced peripheral neuropathy through inhibiting organic cation transporter 2 in mice
citation_author	Ueno, Manami
	Kobayashi, Akihide
	Ikemura, Kenji
	Wakai, Eri
	Yamane, Fumihiro
	Okuda, Masahiro
citation_publisher	Elsevier B.V.
citation_language	英語
citation_date	2025-10-08
citation_journal_title	European Journal of Pharmaceutical Sciences
citation_volume	214
citation_firstpage	107309
citation_doi	https://doi.org/10.1016/j.ejps.2025.107309
citation_public_url	https://hdl.handle.net/11094/103664

Esomeprazole prevents oxaliplatin-induced peripheral neuropathy through inhibiting organic cation transporter 2 in mice

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