Extraction of Uraemic Toxins with Activated Carbon Restores the Functional Properties of Albumin

Abstract

Background: Previous work has demonstrated that a partial normalization of the conformation of albumin from uraemic plasma and a substantial restoration of its binding abilities can be achieved by extraction with activated charcoal. This is best achieved at pH 3, but exposure of whole plasma to this low pH leads to the loss of some essential components. Methods: The melting curves and ligand-binding abilities of uraemic albumin have been investigated after extraction with a new generation of activated carbon at three pH values (7.2, 3.0 and 5.08). Results: Albumin isolated from uraemic plasma had a characteristically increased melting temperature because of bound ligands. Extraction of uraemic plasma at pH 7.2, 5.08 and 3.0 induced low-temperature shifts of albumin thermo-adsorption maximum T₁ of 1.4, 3.8, 2.4°C and T₂ of 0.8, 3.9 and 1.2°C, respectively. Flow microcalorimetry data demonstrated a decrease in the ability of uraemic albumin to bind octanoate, phenol red, salicylic acid, warfarin and diazepam. Purification of uraemic plasma at pH 5.08 completely restored the binding affinity of albumin for all the marker ligands. Conclusions: Highly efficient activated carbons, with clinically feasible acidification of plasma, can remove strongly albumin-bound uraemic toxins. Investigation of the melting curve of the isolated albumin is a new biophysical way to monitor both its molecular condition and the extent of removal of protein-bound toxins by dialysis. The melting curve provides new qualitative and quantitative information about albumin in an analogous way to an electrocardiogram and the heart.

Biophysical Insight into Furosemide Binding to Human Serum Albumin: A Study To Unveil Its Impaired Albumin Binding in Uremia

“…hippuric acid (HA), indoxyl sulfate (IS), 3carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), indole-3 acetic acid (IAA), etc. 17 However, from the available literature, it is found that FUR binds to site I of HSA 11,16,18 whereas all predominant uremic toxins except CMPF bind mainly to site II of HSA. 19−21 So, only CMPF is the uremic toxin that directly inhibits the binding of FUR to albumin as they share the same binding site.…”

“…First, it may be due to some conformational changes in albumin under chronic renal disease but putative structural modifications of pathological HSA have been disputed for decades. − Second, according to the most accepted hypothesis, HSA binding sites might be occupied by uremic toxins, viz. hippuric acid (HA), indoxyl sulfate (IS), 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), indole-3 acetic acid (IAA), etc . However, from the available literature, it is found that FUR binds to site I of HSA ,, whereas all predominant uremic toxins except CMPF bind mainly to site II of HSA. − So, only CMPF is the uremic toxin that directly inhibits the binding of FUR to albumin as they share the same binding site.…”

High-Porosity Activated Carbon as a Possible Matrix For Native DNA and Dextran-Sulfate Immobilization

“…The combination of unspecific adsorptive properties of activated carbonic matrix with the specific adsorption of DNA-coupling substances demonstrates a number of positive clinical effects of the usage of such hemoimmunoadsorbents in the treatment of exacerbations of severe psoriasis and, especially, psoriatic arthropathy, bronchial asthma, lupus nephritis, etc. These adsorptive materials were successfully used for extraction of the most typical protein-bound toxins from blood plasma of patients with hepatic and renal insufficiency Sarnatskaya et al, 2002Sarnatskaya et al, , 2003. Recently, the new type of high-porous carbonic adsorbents having specific internal surface up to 5000 m 2 per 1 g was synthesized in the form of light beads of the regular spherical shape with pronounced mass-fractal organization of its internal dimension.…”