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	Specific hemosiderin deposition in spleen induced by a low dose of cisplatin: altered iron metabolism and its implication as an acute hemosiderin formation model
	Wang, Yingze1,2,3; Lv, Juan3,4; Ma, Xiaowei3; Wang, Dongliang3; Ma, Huili3; Chang, Yanzhong1; Nie, Guangjun3; Jia, Lee3; Duan, Xianglin1; Liang, Xing-Jie3
刊名	Current drug metabolism
	2010-07-01
卷号	11期号:6页码:507-515
关键词	Cp: cis-diamminedichloroplatinum ii Hemosiderin Ferroportin Ferritin Hepcidin
ISSN号	1389-2002
通讯作者	Duan, xianglin(xlduan0311@163.com)
英文摘要	Cisplatin is one of the commonly-used chemotherapeutic drugs to efficiently treat malignant tumors in clinic, however, the adverse effects of cisplatin such as nephrotoxicity, neurotoxcity, and hemolytic uremic syndrome are often observed at its clinical doses (similar to 60 mg/m(2)), which limit its broader application. in earlier studies, little attention was paid to the subtle changes in the architecture of lymphatic organs after low doses of cisplatin treatment. this paper reviews current understanding of cisplatin-induced erythrocyte injury, and presents our latest finding that a low dose of cisplatin (3.6 mg/m(2)/day, 14 days) could induce specific hemosiderin deposition in spleen of both normal and hepatoma-22 (h22) inoculated balb/c mice. this dose of cisplatin significantly inhibited h22-induced acute ascites development. no significant toxicity was induced by this dose of cisplatin to tissues except for hemosiderin accumulation in the spleen of both normal and h22 tumor-bearing mice. increased splenic iron content and erythrocyte injury were observed after treatment with the low dose of cisplatin. the mrna levels of ferroportin (fpn1) and ferritin were upregulated by 25 and 5-fold in spleen, respectively. overexpression of fpn1 and ferritin protein were also been observed at protein levels by western blotting analysis. in addition, the mrna expression of hepcidin was also increased, suggesting blockage of iron recycling through fpn1 in spleen with cisplatin treatment. in conclusion, cisplatin treatment damages the erythrocytes which accumulate in the red pulp of spleen with defective recycling of fpn1 and ferritin protein. hepcidin inhibits the function of fpn1 as iron-exporter leading to iron overloaded inside ferritins of splenic cells, which are stained with abnormal hemosiderin accumulation. these results demonstrate that cisplatin-caused hemosiderin deposition in spleen provides a valuable clue for understanding the molecular basis of toxicity of cisplatin and hemosiderin accumulation and iron metabolism in vivo.
WOS关键词	CELL-LINES ; SPLENIC MACROPHAGES ; FERRITIN ; RATS ; LIVER ; ACCUMULATION ; INFLAMMATION ; FERROPORTIN ; RESISTANCE ; MEMBRANE
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
WOS类目	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
语种	英语
出版者	BENTHAM SCIENCE PUBL LTD
WOS记录号	WOS:000280130100003
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2175988
专题	高能物理研究所
通讯作者	Duan, Xianglin
作者单位	1.Hebei Normal Univ, Coll Life Sci, Lab Mol Iron Metab, Shijiazhuang 050016, Peoples R China 2.Hebei Univ Sci & Technol, Coll Biosci & Bioengn, Shijiazhuang 050018, Peoples R China 3.Natl Ctr Nanosci & Technol China, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China 4.Peking Univ, Sch Oncol, Key Lab Carcinogenesis & Translat Res, Dept Biochem & Mol Biol, Beijing 100142, Peoples R China
推荐引用方式 GB/T 7714	Wang, Yingze,Lv, Juan,Ma, Xiaowei,et al. Specific hemosiderin deposition in spleen induced by a low dose of cisplatin: altered iron metabolism and its implication as an acute hemosiderin formation model[J]. Current drug metabolism,2010,11(6):507-515.
APA	Wang, Yingze.,Lv, Juan.,Ma, Xiaowei.,Wang, Dongliang.,Ma, Huili.,...&Liang, Xing-Jie.(2010).Specific hemosiderin deposition in spleen induced by a low dose of cisplatin: altered iron metabolism and its implication as an acute hemosiderin formation model.Current drug metabolism,11(6),507-515.
MLA	Wang, Yingze,et al."Specific hemosiderin deposition in spleen induced by a low dose of cisplatin: altered iron metabolism and its implication as an acute hemosiderin formation model".Current drug metabolism 11.6(2010):507-515.

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