Influence of Piracetam on Gliclazide—Glycated Human Serum Albumin Interaction. A Spectrofluorometric Study

Abstract

Advanced Glycation End-Products (AGEs) are created in the last step of protein glycation and can be a factor in aging and in the development or worsening of many degenerative diseases (diabetes, chronic kidney disease, atherosclerosis, Alzheimer’s disease, etc.). Albumin is the most susceptible to glycation plasma protein. Modified albumin by AGEs may be more resistant to enzymatic degradation, which further increases the local accumulation of AGEs in tissues. The aim of the present study was to analyze in vitro glycation of serum albumin in the presence of piracetam (PIR) and the gliclazide (GLZ)-glycated albumin interaction. The analysis of PIR as an inhibitor and GLZ interaction with nonglycated human albumin (HSA) and glycated by fructose human albumin (gHSAFRC), in the absence and presence of piracetam (gHSAFRC-PIR), was performed by fluorescence quenching of macromolecules. On the basis of obtained data we concluded that under the influence of glycation, association constant (Ka) of gliclazide to human serum albumin decreases and GLZ binds to HSA with less strength than under physiological conditions. PIR strongly inhibited the formation of AGEs in the system where the efficiency of HSA glycation was the largest. The analysis of piracetam influence on the GLZ-glycated albumin interaction has shown that piracetam increases the binding strength of GLZ to glycated albumin and weakens its therapeutic effect. Based on the obtained data we concluded that monitoring therapy and precautions are required in the treatment when the combinations of gliclazide and piracetam are used at the same time.

How Does Glycation Affect Binding Parameters of the Albumin-Gliclazide System in the Presence of Drugs Commonly Used in Diabetes? In Vitro Spectroscopic Study

“…In our study K a for ternary complexes they varied from 0.11 to 1.07 × 10 4 M −1 . Similar effects and variations, in affinity at comparable levels of glycation, have been noted in recent studies examining the binding of sulfonylureas with glycated HSA both in vitro and in vivo [9,33]. On the other hand, some researchers observed increased K a values upon glycation [25,34].…”

“…Therefore, we conclude that the contribution of tyrosyl residues in the interaction of DRUG-GLICL is negligible, independently from glycation. Szkudlarek et al [9] have shared a similar observation with regard to gliclazide and glycated HSA. Since BSA has two tryptophanyl residues (Trp134 and Trp213), this phenomenon is even more pronounced than for HSA with a single tryptophan.…”

“…Szkudlarek et al [9] have shared a similar observation with regard to gliclazide and glycated HSA. Since BSA has two tryptophanyl residues (Trp134 and Trp213), this phenomenon is even more pronounced than for HSA with a single tryptophan.…”

“…Diabetic patients are considered to have a 2-3-fold higher level of glycated albumin compared with healthy subjects [5]. Since many pharmacological agents extensively bind to plasma albumin, it is important to know how this process can be altered under hyperglycemic conditions and in the presence of other drugs (protein-displacing interactions), and such investigations are intensively conducted [6][7][8][9].…”

Preparation and characterization of curcumin‐loaded polymeric nanomicelles to interference with amyloidogenesis through glycation method

“…As described earlier in this study, fructose attached to albumin fibers through the free amines of lysine and led to protein fibers structural conversion from α‐helical to β‐sheet. As attachment increases, glycation and AGE products generation would be more and therefore β‐sheet formation increases . To evaluate the number of AGE products, autofluorescence of these groups were measured and the results were recorded as graphs.…”