The processes and mechanism of antimony sequestered by red blood cells and its metabolic conjugation with hemoglobin in rats. (1st September 2018)

• Record Type: Journal Article
• Authors: Wu, Zhijun; Cheng, Juan; Guo, Xuejun; Ding, Chunguang; Jin, Xin; Ren, Qidong; Zheng, Min; Wang, Lei; Zhao, Wenjin
• Is Part Of: Toxicology. Volume 408(2018)
• Page Start: 46
• Page End: 53
• Publication Date: 2018-09-01
• Subjects: Antimony (Sb) -- Red blood cells (RBCs) -- Hemoglobin (Hb) -- Accumulation -- Metabolism; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2018.06.006
• Languages: English
• ISSNs: 0300-483X

Abstract

Highlights: Mechanism of Sb accumulated in RBCs was explored by in vitro and in vivo studies. Parent form of Sb had notable affinity with RBCs but negligible affinity with Hb. In vivo studies demonstrated that most of Sb metabolites were integrated into Hb. Liver metabolism played a potential role influencing Sb's partitioning in blood. Nano-HPLC–MS/MS suggested Sb(CH3 )2 O2 H conjugated with Hb (α chain, Cys104/Cys111). Abstract: Toxicity of antimony (Sb) to humans may occur through environmental, occupational, and therapeutic exposures. The underlying mechanism of its accumulation in red blood cells (RBCs) is not clear. Here, the processes and mechanism of RBCs sequestering Sb were explored through a series of in vitro and in vivo studies. These include binding affinity of Sb compounds with rat hemoglobin (Hb) and RBCs, acute exposure of antimony potassium tartrate (APT III ), and subchronic oral exposure of APT III, potassium pyroantimonate (PP V ) and antimony trioxide (AT III ). In vitro study indicated that parent form of Sb exhibited notable affinity with RBCs, while represented negligible affinity with Hb. However, after acute exposure to APT III, over 93% of Sb in rat blood was integrated into Hb. Sb retaining in liver homogenate supernatants was substantially integrated into Hb, which indicated liver metabolism played a potential role influencing its ultimate partitioning in blood. Subchronic exposure of APT III, PP V and AT III to rats also demonstrated that most of Sb metabolites were integrated into Hb, regardless of which Sb compounds administered. Nano-HPLC–MS/MS analysis suggested that a dimethylated Sb species in pentavalent state [Sb(CH3 )2 O2 H] was a major Sb group conjugated with Hb at Cys 104 and Cys 111 especially, in α chain of rat Hb. Hb-conjugated Sb did not affect Hb's oxygen binding capability. As the deposit sites for both the parent forms and the metabolite, Sb re-released to circulation system due to RBCs and Hb degradation could have high substantial toxicological effects on its potential sites of action.