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Omeprazole Suppresses Oxaliplatin-Induced Peripheral Neuropathy in a Rodent Model and Clinical Database

(1) Background: Oxaliplatin is used as first-line chemotherapy not only for colorectal cancer but also for gastric and pancreatic cancers. However, it induces peripheral neuropathy with high frequency as an adverse event, and there is no effective preventive or therapeutic method. (2) Methods: The e...

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Autores principales: Mine, Keisuke, Kawashiri, Takehiro, Inoue, Mizuki, Kobayashi, Daisuke, Mori, Kohei, Hiromoto, Shiori, Kudamatsu, Hibiki, Uchida, Mayako, Egashira, Nobuaki, Koyanagi, Satoru, Ohdo, Shigehiro, Shimazoe, Takao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408309/
https://www.ncbi.nlm.nih.gov/pubmed/36012136
http://dx.doi.org/10.3390/ijms23168859
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author Mine, Keisuke
Kawashiri, Takehiro
Inoue, Mizuki
Kobayashi, Daisuke
Mori, Kohei
Hiromoto, Shiori
Kudamatsu, Hibiki
Uchida, Mayako
Egashira, Nobuaki
Koyanagi, Satoru
Ohdo, Shigehiro
Shimazoe, Takao
author_facet Mine, Keisuke
Kawashiri, Takehiro
Inoue, Mizuki
Kobayashi, Daisuke
Mori, Kohei
Hiromoto, Shiori
Kudamatsu, Hibiki
Uchida, Mayako
Egashira, Nobuaki
Koyanagi, Satoru
Ohdo, Shigehiro
Shimazoe, Takao
author_sort Mine, Keisuke
collection PubMed
description (1) Background: Oxaliplatin is used as first-line chemotherapy not only for colorectal cancer but also for gastric and pancreatic cancers. However, it induces peripheral neuropathy with high frequency as an adverse event, and there is no effective preventive or therapeutic method. (2) Methods: The effects of omeprazole, a proton pump inhibitor (PPI), on oxaliplatin-induced peripheral neuropathy (OIPN) was investigated using an in vivo model and a real-world database. (3) Results: In a rat model, oxaliplatin (4 mg/kg, i.p., twice a week for 4 weeks) caused mechanical hypersensitivity accompanied by sciatic nerve axonal degeneration and myelin sheath disorder. Repeated injection of omeprazole (5–20 mg/kg, i.p., five times per week for 4 weeks) ameliorated these behavioral and pathological abnormalities. Moreover, omeprazole did not affect the tumor growth inhibition of oxaliplatin in tumor bearing mice. Furthermore, clinical database analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) suggests that the group using omeprazole has a lower reporting rate of peripheral neuropathy of oxaliplatin-treated patients than the group not using (3.06% vs. 6.48%, p < 0.001, reporting odds ratio 0.44, 95% confidence interval 0.32–0.61). (4) Conclusions: These results show the preventing effect of omeprazole on OIPN.
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spelling pubmed-94083092022-08-26 Omeprazole Suppresses Oxaliplatin-Induced Peripheral Neuropathy in a Rodent Model and Clinical Database Mine, Keisuke Kawashiri, Takehiro Inoue, Mizuki Kobayashi, Daisuke Mori, Kohei Hiromoto, Shiori Kudamatsu, Hibiki Uchida, Mayako Egashira, Nobuaki Koyanagi, Satoru Ohdo, Shigehiro Shimazoe, Takao Int J Mol Sci Article (1) Background: Oxaliplatin is used as first-line chemotherapy not only for colorectal cancer but also for gastric and pancreatic cancers. However, it induces peripheral neuropathy with high frequency as an adverse event, and there is no effective preventive or therapeutic method. (2) Methods: The effects of omeprazole, a proton pump inhibitor (PPI), on oxaliplatin-induced peripheral neuropathy (OIPN) was investigated using an in vivo model and a real-world database. (3) Results: In a rat model, oxaliplatin (4 mg/kg, i.p., twice a week for 4 weeks) caused mechanical hypersensitivity accompanied by sciatic nerve axonal degeneration and myelin sheath disorder. Repeated injection of omeprazole (5–20 mg/kg, i.p., five times per week for 4 weeks) ameliorated these behavioral and pathological abnormalities. Moreover, omeprazole did not affect the tumor growth inhibition of oxaliplatin in tumor bearing mice. Furthermore, clinical database analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) suggests that the group using omeprazole has a lower reporting rate of peripheral neuropathy of oxaliplatin-treated patients than the group not using (3.06% vs. 6.48%, p < 0.001, reporting odds ratio 0.44, 95% confidence interval 0.32–0.61). (4) Conclusions: These results show the preventing effect of omeprazole on OIPN. MDPI 2022-08-09 /pmc/articles/PMC9408309/ /pubmed/36012136 http://dx.doi.org/10.3390/ijms23168859 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mine, Keisuke
Kawashiri, Takehiro
Inoue, Mizuki
Kobayashi, Daisuke
Mori, Kohei
Hiromoto, Shiori
Kudamatsu, Hibiki
Uchida, Mayako
Egashira, Nobuaki
Koyanagi, Satoru
Ohdo, Shigehiro
Shimazoe, Takao
Omeprazole Suppresses Oxaliplatin-Induced Peripheral Neuropathy in a Rodent Model and Clinical Database
title Omeprazole Suppresses Oxaliplatin-Induced Peripheral Neuropathy in a Rodent Model and Clinical Database
title_full Omeprazole Suppresses Oxaliplatin-Induced Peripheral Neuropathy in a Rodent Model and Clinical Database
title_fullStr Omeprazole Suppresses Oxaliplatin-Induced Peripheral Neuropathy in a Rodent Model and Clinical Database
title_full_unstemmed Omeprazole Suppresses Oxaliplatin-Induced Peripheral Neuropathy in a Rodent Model and Clinical Database
title_short Omeprazole Suppresses Oxaliplatin-Induced Peripheral Neuropathy in a Rodent Model and Clinical Database
title_sort omeprazole suppresses oxaliplatin-induced peripheral neuropathy in a rodent model and clinical database
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408309/
https://www.ncbi.nlm.nih.gov/pubmed/36012136
http://dx.doi.org/10.3390/ijms23168859
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