Reactivity and Speciation of Anti-Diabetic Vanadium Complexes in Whole Blood and Its Components: The Important Role of Red Blood Cells

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• 作者：Aviva Levina ; Andrew I. McLeod ; Sylvia J. Gasparini ; Annie Nguyen ; W. G. Manori De Silva ; Jade B. Aitken ; Hugh H. Harris ; Chris Glover ; Bernt Johannessen ; Peter A. Lay
• 刊名：Inorganic Chemistry
• 出版年：2015
• 出版时间：August 17, 2015
• 年：2015
• 卷：54
• 期：16
• 页码：7753-7766
• 全文大小：883K
• ISSN：1520-510X

文摘

Reactions with blood components are crucial for controlling the antidiabetic, anticancer, and other biological activities of V(V) and V(IV) complexes. Despite extensive studies of V(V) and V(IV) reactions with the major blood proteins (albumin and transferrin), reactions with whole blood and red blood cells (RBC) have been studied rarely. A detailed speciation study of Na₃[V^VO₄] (A), K₄[V^IV₂O₂(citr)₂]路6H₂O (B; citr = citrato(4鈭?); [V^IVO(ma)₂] (C; ma = maltolato(鈭?), and (NH₄)[V^V(O)₂(dipic)] (D; dipic = pyridine-2,6-dicarboxylato(2鈭?) in whole rat blood, freshly isolated rat plasma, and commercial bovine serum using X-ray absorption near-edge structure (XANES) spectroscopy is reported. The latter two compounds are potential oral antidiabetic drugs, and the former two are likely to represent their typical decomposition products in gastrointestinal media. XANES spectral speciation was performed by principal component analysis and multiple linear regression techniques, and the distribution of V between RBC and plasma fractions was measured by electrothermal atomic absorption spectroscopy. Reactions of A, C, or D with whole blood (1.0 mM V, 1鈥? h at 310 K) led to accumulation of 鈭?0% of total V in the RBC fraction (鈭?0% in the case of B), which indicated that RBC act as V carriers to peripheral organs. The spectra of V products in RBC were independent of the initial V complex, and were best fitted by a combination of V(IV)鈥揷arbohydrate (2-hydroxyacid moieties) and/or citrate (65鈥?5%) and V(V)鈥損rotein (15鈥?5%) models. The presence of RBC created a more reducing environment in the plasma fraction of whole blood compared with those in isolated plasma or serum, as shown by the differences in distribution of V(IV) and V(V) species in the reaction products of A鈥?b>D in these media. At physiologically relevant V concentrations (<50 渭M), this role of RBC may promote the formation of V(III)-transferrin as a major V carrier in the blood plasma. The results reported herein have broad implications for the roles of RBC in the transport and speciation of metal pro-drugs that have broad applications across medicine.