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Mar Drugs ; 20(3)2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35323500

RESUMO

Hematopoietic damage is a serious side effect of cytotoxic drugs, and agents promoting hematopoiesis are quite important for decreasing the death rate in cancer patients. In our previous work, we prepared the simulated digestive product of fucoidan from Sargassum fusiforme, DSFF, and found that DSFF could activate macrophages. However, more investigations are needed to further evaluate whether DSFF could promote hematopoiesis in the chemotherapy process. In this study, the protective effect of DSFF (1.8-7.2 mg/kg, i.p.) on cyclophosphamide-induced hematopoietic damage in mice and the underlying mechanisms were investigated. Our results show that DSFF could restore the numbers of white blood cells, neutrophils, and platelets in the peripheral blood, and could also retard bone marrow cell decrease in mice with cyclophosphamide-induced hematopoietic damage. UPLC/Q-Extraction Orbitrap/MS/MS-based lipidomics results reveal 16 potential lipid biomarkers in a serum that responded to hematopoietic damage in mice. Among them, PC (20:1/14:0) and SM (18:0/22:0) were the key lipid molecules through which DSFF exerted protective actions. In a validation experiment, DSFF (6.25-100 µg/mL) could also promote K562 cell proliferation and differentiation in vitro. The current findings indicated that DSFF could affect the blood cells and bone marrow cells in vivo and thus showed good potential and application value in alleviating the hematopoietic damage caused by cyclophosphamide.


Assuntos
Ciclofosfamida/toxicidade , Hematopoese/efeitos dos fármacos , Agonistas Mieloablativos/toxicidade , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Sargassum , Animais , Biomarcadores/sangue , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Proliferação de Células/efeitos dos fármacos , DNA/metabolismo , Humanos , Células K562 , Contagem de Leucócitos , Lipidômica , Camundongos , Neutrófilos/efeitos dos fármacos , Contagem de Plaquetas
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