Interactions of zearalenone and its reduced metabolites α-zearalenol and β-zearalenol with serum albumins: species differences, binding sites, and thermodynamics

Abstract

Zearalenone (ZEN) is a mycotoxin produced by Fusarium species. ZEN mainly appears in cereals and related foodstuffs, causing reproductive disorders in animals, due to its xenoestrogenic effects. The main reduced metabolites of ZEN are α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL). Similarly to ZEN, ZELs can also activate estrogen receptors; moreover, α-ZEL is the most potent endocrine disruptor among these three compounds. Serum albumin is the most abundant plasma protein in the circulation; it affects the tissue distribution and elimination of several drugs and xenobiotics. Although ZEN binds to albumin with high affinity, albumin-binding of α-ZEL and β-ZEL has not been investigated. In this study, the complex formation of ZEN, α-ZEL, and β-ZEL with human (HSA), bovine (BSA), porcine (PSA), and rat serum albumins (RSA) was investigated by fluorescence spectroscopy, affinity chromatography, thermodynamic studies, and molecular modeling. Our main observations are as follows: (1) ZEN binds with higher affinity to albumins than α-ZEL and β-ZEL. (2) The low binding affinity of β-ZEL toward albumin may result from its different binding position or binding site. (3) The binding constants of the mycotoxin-albumin complexes significantly vary with the species. (4) From the thermodynamic point of view, the formation of ZEN-HSA and ZEN-RSA complexes are similar, while the formation of ZEN-BSA and ZEN-PSA complexes are markedly different. These results suggest that the toxicological relevance of ZEN-albumin and ZEL-albumin interactions may also be species-dependent.

Interaction of the mycotoxin metabolite dihydrocitrinone with serum albumin

“…3). Decimal logarithmic values of Stern-Volmer quenching constants (KSV; unit: L/mol) and binding constants (K; unit: L/mol) are demonstrated in Table 1 (Faisal et al, 2018). From this point of view, DHC behaves very similarly to the parent compound CIT; the latter binds to HSA with almost the same affinity (logK = 5.32) and shows similar species differences to DHC (Poór et al, 2015).…”

“…Binding constants (K) of DHC-albumin complexes were determined by non-linear fitting, using the Hyperquad2006 program package (Protonic Software), during which the following equations were implemented in the Hyperquad code (SA: serum albumin) (Faisal et al, 2018):…”

Testing the Pharmacokinetic Interactions of 24 Colonic Flavonoid Metabolites with Human Serum Albumin and Cytochrome P450 Enzymes

“…In quenching studies, the emission spectrum of HSA (2 µM) was recorded in the presence of increasing concentrations of microbial metabolites (0, 2, 3, 4, 5, 6, and 8 µM), using a 295 nm excitation wavelength. Data were evaluated based on linear and non-linear fitting, employing the Stern-Volmer equation (Equation (2)) and the Hyperquad2006 program package (Protonic Software; Leeds, UK) [30,31], respectively. The Stern-Volmer equation was described as…”

“…The fluorescence emission spectrum of 2H4MBA (2 µM) was recorded with HSA (0, 0.5, 1, 2, 3, 4 and 5 µM), using 295 nm excitation wavelength (the excitation maximum of 2H4MBA). The binding constants (K; unit: L/mol) of albumin-ligand complexes were determined by non-linear fitting using the Hyperquad2006 program, as has been reported [30,31]. During this evaluation, absorbance values and fluorescence signals of both HSA and 2H4MBA were taken into account.…”

“…This suggests the formation of 2H4MBA-HSA complexes. Based on quenching studies (Figure 2) and the HSA-induced increase in the fluorescence of 2H4MBA (Figure 4), the binding constants (K) of albumin-ligand complexes were determined by non-linear fitting, employing the Hyperquad2006 software [30,31]. Table 1 demonstrates the decimal logarithmic K values, suggesting that 2H4MBA and DESMA binds to albumin with the highest affinity among the compounds tested.…”