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 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | Japanese |
Published |
公益社団法人 日本薬理学会
2022
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Subjects | |
Online Access | Get full text |
ISSN | 2435-4953 |
DOI | 10.1254/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. |
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Bibliography: | 96_2-B-O04-4 |
ISSN: | 2435-4953 |
DOI: | 10.1254/jpssuppl.96.0_2-B-O04-4 |