In Vitro Investigations of Acetohexamide Binding to Glycated Serum Albumin in the Presence of Fatty Acid

Molecules. 2020 May 17;25(10):2340. doi: 10.3390/molecules25102340.

Abstract

The interaction of drugs with human serum albumin (HSA) is an important element of therapy. Albumin affects the distribution of the drug substance in the body, as well as its pharmacokinetic and pharmacodynamic properties. On the one hand, inflammation and protein glycation, directly associated with many pathological conditions and old age, can cause structural and functional modification of HSA, causing binding disorders. On the other hand, the widespread availability of various dietary supplements that affect the content of fatty acids in the body means that knowledge of the binding activity of transporting proteins, especially in people with chronic diseases, e.g., diabetes, will achieve satisfactory results of the selected therapy. Therefore, the aim of the present study was to evaluate the effect of a mixture of fatty acids (FA) with different saturated and unsaturated acids on the affinity of acetohexamide (AH), a drug with hypoglycaemic activity for glycated albumin, simulating the state of diabetes in the body. Based on fluorescence studies, we can conclude that the presence of both saturated and unsaturated FA disturbs the binding of AH to glycated albumin. Acetohexamide binds more strongly to defatted albumin than to albumin in the presence of fatty acids. The competitive binding of AH and FA to albumin may influence the concentration of free drug fraction and thus its therapeutic effect.

Keywords: acetohexamide; fluorescence and UV-Vis spectroscopy; glycation; human serum albumin; saturated and unsaturated fatty acids.

MeSH terms

  • Acetohexamide / chemistry*
  • Binding, Competitive
  • Fatty Acids / chemistry*
  • Glucose / chemistry
  • Glycated Serum Albumin
  • Glycation End Products, Advanced
  • Humans
  • Hypoglycemic Agents / chemistry*
  • Linoleic Acid / chemistry
  • Molecular Dynamics Simulation
  • Myristic Acid / chemistry
  • Oleic Acid / chemistry
  • Palmitic Acid / chemistry
  • Protein Binding
  • Protein Conformation
  • Serum Albumin / chemistry*
  • Serum Albumin, Human / chemistry*
  • Solutions

Substances

  • Fatty Acids
  • Glycation End Products, Advanced
  • Hypoglycemic Agents
  • Serum Albumin
  • Solutions
  • Myristic Acid
  • Oleic Acid
  • Palmitic Acid
  • Linoleic Acid
  • Glucose
  • Acetohexamide
  • Serum Albumin, Human
  • Glycated Serum Albumin