Stimulating the Hematopoietic Effect of Simulated Digestive Product of Fucoidan from Sargassum fusiforme on Cyclophosphamide-Induced Hematopoietic Damage in Mice and Its Protective Mechanisms Based on Serum Lipidomics.

Wei-Ping Ma,Xi-Cheng Geng,Shi-Ning Yin,Jia-Peng Chen,Hong-Bing Liu,Ming Liu,Ming-Fei Liu,Hai-Hua Li

doi:10.3390/md20030201

Abstract

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.

Highlights

Cytotoxic drugs are the first-line drugs used in the clinical treatment of malignant tumors [1], but they cause some serious side effects, such as hematopoietic damage [2], bone marrow suppression [3], and immunosuppression [4], which significantly increase the risk of death in cancer patients
Sea cucumber fucoidan (Holothuria Polii) could restore the number of white blood cells reduced by cyclophosphamide and significantly promote the recovery of neutrophils [10]; brown algae (Chordaria flagelliformis) fucoidan was shown to promote the recovery of the white blood cell count in mice with cyclophosphamide-induced leukopenia [11]
These results indicate that digestive product of fucoidan from Sargassum fusiforme (DSFF) might have a potential alleviation effect on the inhibition of body weight gain induced by cyclophosphamide

Summary

Introduction

Cytotoxic drugs are the first-line drugs used in the clinical treatment of malignant tumors [1], but they cause some serious side effects, such as hematopoietic damage [2], bone marrow suppression [3], and immunosuppression [4], which significantly increase the risk of death in cancer patients. The polysaccharides found in traditional Chinese medicines have been found to protect against the hematopoietic damage caused by cytotoxic drugs and even enhance the immune state of the body [8]. Changes in various lipid molecule levels have been observed in hematopoietic abnormalities and might be considered markers for disease monitoring and treatment [16]; they might affect peripheral blood hematopoietic stem cell levels [17]. Sargassum fusiforme fucoidan was reported to regulate lipid metabolism levels [18]. We hypothesized that the macrophage activation, the phenotype polarization effect, and the lipid regulation of DSFF have the potential to alleviate chemical drug-induced hematopoietic damage. It is interesting and worthwhile to investigate the hematopoietic damage protection of DSFF in vivo and its protective mechanisms

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Conclusion