Elimination of Endogenous Toxin, Creatinine from Blood Plasma Depends on Albumin Conformation: Site Specific Uremic Toxicity & Impaired Drug Binding

Abstract

Uremic syndrome results from malfunctioning of various organ systems due to the retention of uremic toxins which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. The aim of this study was to elucidate the mechanisms underlying the renal elimination of uremic toxin creatinine that accumulate in chronic renal failure. Quantitative investigation of the plausible correlations was performed by spectroscopy, calorimetry, molecular docking and accessibility of surface area. Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination. The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding. These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state.

The Quantitative Effect of Serum Albumin, Serum Urea, and Valproic Acid on Unbound Phenytoin Concentrations in Children

“…Furthermore, our study is the first to confirm the influence of elevated serum urea concentrations on the protein binding of phenytoin in children. Although the biochemical parameters serum urea and serum creatinine are correlated and both influenced protein binding of phenytoin in the univariate analysis, serum urea concentrations can be a better marker for accumulation of uremic toxins than serum creatinine based on the facts that uremic toxins are able to bind to albumin and displace protein-bound drugs 30,31 and that the relationship of serum creatinine with renal function in very young children is different from that in young adults. 32 Even though our study suggests that changes in serum urea concentrations significantly influence the unbound fraction, this effect is rather small and perhaps not clinically relevant in children with a modestly increased serum urea concentration.…”

Calorimetric and spectroscopic binding studies of amoxicillin with human serum albumin

“…FTIR spectra of proteins exhibit a number of amide bands, which represent different vibrations of the peptide moiety. Among all the amide bands, the amide I band appears at 1700-1600 cm -1 due to C=O stretch, and amide II band appears at 1600-1500 cm -1 and is associated with C-N stretch and N-H bending mode having relationship with the conformation of proteins [39]. In the two bands, amide I is more sensitive to the changes in protein secondary structure than amide II.…”

Probing the binding of an endocrine disrupting compound-Bisphenol F to human serum albumin: Insights into the interactions of harmful chemicals with functional biomacromolecules

“…It contains many kinds of coordinating groups, which can combine with many endogenous and exogenous compounds [15][16][17]. Although the toxicity studies of BPF have been reported, the particular interaction mechanism, the mode of BPF with serum albumin and its effect on protein conformation are still unknown.…”