オキサリプラチン誘起末梢神経障害(OIPN)への血小板由来HMGB1の関与:抗血小板薬のOIPN予防効果について

HMGB1, a nuclear protein, once released extracellularly, promotes inflammation and pain. We have shown the involvement of macrophage-derived HMGB1 in chemotherapy-induced peripheral neuropathy (CIPN) caused by paclitaxel, bortezomib or vincristine, and of non-macrophage cell-derived HMGB1 in CIPN ca...

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Published in日本薬理学会年会要旨集 p. 2-B-O04-4
Main Authors 川畑, 篤史, 王, 登莉, 岸本, 彩野, 堂本, 莉紗, 松永, 浩明, 坪田, 真帆, 松本, 亜紗菜, 西堀, 正洋, 関口, 富美子
Format Journal Article
LanguageJapanese
Published 公益社団法人 日本薬理学会 2022
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ISSN2435-4953
DOI10.1254/jpssuppl.96.0_2-B-O04-4

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Summary:HMGB1, a nuclear protein, once released extracellularly, promotes inflammation and pain. We have shown the involvement of macrophage-derived HMGB1 in chemotherapy-induced peripheral neuropathy (CIPN) caused by paclitaxel, bortezomib or vincristine, and of non-macrophage cell-derived HMGB1 in CIPN caused by oxaliplatin (OIPN). Given the involvement of platelet-derived HMGB1 in thrombosis, we asked whether the pathogenesis of OIPN would involve platelet-derived HMGB1 in rodents. In rat platelet-rich plasma (PRP), thrombin induced HMGB1 release from platelets. An anti-CD42b platelet-depleting antibody dramatically decreased platelet count and increased plasma HMGB1 levels in mice, leading to OIPN development after subsequent oxaliplatin treatment at a subeffective dose. Splenectomy almost doubled platelet count and accelerated OIPN development. Repeated oral administration of different antiplatelet agents, aspirin, clopidogrel, cilostazol and ozagrel, prevented OIPN development in mice and/or rats. In rats subjected to repeated treatment with oxaliplatin, HMGB1 levels dramatically decreased in PRP, but tended to increase in platelet-poor plasma. Together, our study provides novel evidence for a critical role of platelet-derived HMGB1 in OIPN development, and suggests the usefulness of antiplatelet agents to prevent severe OIPN.
Bibliography:96_2-B-O04-4
ISSN:2435-4953
DOI:10.1254/jpssuppl.96.0_2-B-O04-4