Abstract
The speciation of Cu2+, Ni2+ and Zn2+ ions in the presence of the fluoroquinolones (FQs) moxifloxacin, ofloxacin, levofloxacin and ciprofloxacin, in human blood plasma was studied under physiological conditions by computer simulation. The speciation was calculated using an updated model of human blood plasma including over 6,000 species with the aid of the program Hyss2009. The identity and stability of metal-FQ complexes were determined by potentiometric (310 K, 0.15 mol/L NaCl), spectrophotometric, spectrofluorimetric, ESI-MS and 1H-NMR measurements. In the case of Cu2+ ion the concentration of main low molecular weight (LMW) plasma complex (Cu(Cis)His) is very slightly influenced by all examined FQs. FQs show much higher influence on main plasma Ni2+ and Zn2+ complexes: (Ni(His)2 and Zn(Cys)Cit, respectively. Levofloxacin exhibits the highest influence on the fraction of the main nickel complex, Ni(His)2, even at a concentration level of 3 × 10−5 mol/L. The same effect is seen on the main zinc complex, Zn(Cys)Cit. Calculated plasma mobilizing indexes indicate that ciprofloxacin possesses the highest mobilizing power from plasma proteins, toward copper ion, while levofloxacin is the most influential on nickel and zinc ions. The results obtained indicate that the drugs studied are safe in relation to mobilization of essential metal ions under physiological conditions. The observed effects were explained in terms of competitive equilibrium reactions between the FQs and the main LMW complexes of the metal ions.
Highlights
Elemental speciation in biological fluids, human plasma, implies investigation of the association between the trace element and available bioligands: proteins and compounds with relatively low molecular weight (LMW)
In this work we studied the effect of a number of FQs on the biodistribution of Cu2+, Ni2+ and Zn2+ ions using the equilibrium calculations method
Computer simulations are a useful way of predicting the effect of various exogenous ligands on the biodistribution of essential metal ions in biological fluids and tissues, in human blood plasma
Summary
Elemental speciation in biological fluids, human plasma, implies investigation of the association between the trace element and available bioligands: proteins and compounds with relatively low molecular weight (LMW). These investigations constitute a basis of metabolic and kinetic studies and are used to explain the mobility, storage retention and toxicity of metal ions [1]. Two approaches are common: (a) minimization of total Gibbs-free energy of the multi-component system, subjected to the constraints of the elemental mass balance This approach is used in geochemical and chemical engineering simulations; and (b) equilibrium calculations based on calculation of concentrations by solving the system of mass balance equations
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