Norcantharidin down-regulates iron contents in the liver and spleen of lipopolysaccharide-treated mice. (31st December 2022)

• Record Type: Journal Article
• Authors: Zheng, Jie; Wang, Jiao-Jiao; Ma, Hui-Min; Shen, Meng-Qi; Qian, Zhong-Ming; Bao, Yu-Xin
• Is Part Of: Redox report. Volume 27:Number 1(2022)
• Page Start: 119
• Page End: 127
• Publication Date: 2022-12-31
• Subjects: Norcantharidin (NCTD) -- tissue iron -- TfR1 and Fpn1 -- IRP1 and hepcidin -- IL-6/JAK2/STAT3 signaling pathway -- mice -- liver -- spleen; Free radicals (Chemistry) -- Pathophysiology -- Periodicals; Oxidation, Physiological -- Periodicals; 541.224
• DOI: 10.1080/13510002.2022.2088011
• Languages: English
• ISSNs: 1351-0002

Abstract

ABSTRACT: Objective: The inhibiting effect of Norcantharidin (NCTD) on IL-6 (interleukin-6) and STAT3 and the involvement of the IL-6/STAT3 pathway in hepcidin expression prompted us to speculate that NCTD could affect iron metabolism. Methods : We examined the effects of NCTD on serum iron (SI) and transferrin (Tf) saturation, iron and ferritin light chain (FTL), transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), ferroportin 1 (Fpn1), iron regulatory protein 1 (IRP1) and hepcidin, as well as IL-6 and STAT3 in the liver, spleen and duodenum of mice treated with lipopolysaccharide (LPS) in vivo, using RT-PCR, Western blotting and immunofluorescence analysis. Results : NCTD could increase SI and Tf saturation and reduce tissue iron and FTL content by affecting expression of cell-iron transport proteins TfR1, DMT1 and Fpn1. The impact of NCTD on TfR1, DMT1 and Fpn1 expression is mediated by up-regulating IRP1 and down-regulating hepcidin expression, while NCTD-induced down-regulation of hepcidin is mediated by the IL-6/STAT3 signalling pathway in LPS-treated mice. Conclusions : NCTD affects iron metabolism by modifying the expression of IL-6/JAK2/STAT3/hepcidin and IRP1 and suggest that the ability of NCTD to reduce tissue iron contents may be a novel mechanism associated with the anti-cancer effects of NCTD.