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Toxicology. 2018 Sep 1;408:46-53. doi: 10.1016/j.tox.2018.06.006. Epub 2018 Jun 13.

The processes and mechanism of antimony sequestered by red blood cells and its metabolic conjugation with hemoglobin in rats.

Author information

1
The Toxicology Laboratory of National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, 100050, China; State Key Laboratory of Environment Simulation, School of Environment, Beijing Normal University, No. 19 Xinjiekouwai Street, Beijing, 100875, China.
2
The Toxicology Laboratory of National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, 100050, China.
3
State Key Laboratory of Environment Simulation, School of Environment, Beijing Normal University, No. 19 Xinjiekouwai Street, Beijing, 100875, China. Electronic address: guoxj@bnu.edu.cn.
4
Occupational Hazard Analysis and Research Center, National Center of Occupational Safety and Health, Beijing, 102308, China.
5
State Key Laboratory of Environment Simulation, School of Environment, Beijing Normal University, No. 19 Xinjiekouwai Street, Beijing, 100875, China.

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 (APTIII), and subchronic oral exposure of APTIII, potassium pyroantimonate (PPV) and antimony trioxide (ATIII). 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 APTIII, 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 APTIII, PPV and ATIII 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)2O2H] 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.

KEYWORDS:

Accumulation; Antimony (Sb); Hemoglobin (Hb); Metabolism; Red blood cells (RBCs)

PMID:
29908219
DOI:
10.1016/j.tox.2018.06.006
[Indexed for MEDLINE]

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