Structural Changes of Apolipoprotein A-I Caused by Hydroxyethyl Starch 130/0.4 Reveals Potential Toxic Mechanisms

Abstract

6% hydroxyethyl starch (HES 130/0.4) is frequently employed to address hypovolemia, ensuring sufficient organ perfusion and oxygen transport. The effects on Apolipoprotein A-I (ApoA-I) were examined at three temperatures-280, 295, and 310 K-through several spectroscopic techniques to explore its possible interaction with the predominant protein in veins. The experimental findings indicated that HES 130/0.4 efficiently extinguished the intrinsic fluorescence of APOA-I. We also assessed the binding sites, binding constant, and thermodynamic parameters, which indicated that HES 130/0.4 can spontaneously associate with APOA-I via hydrogen bonds and van der Waals interactions (ΔG = - 1.93 × 10⁴ J·mol^-1, ΔH = - 5.63 × 10⁴ J mol⁻¹, and ΔS = - 119 J mol⁻¹ K⁻¹) with a single binding site and week binding forces (n = 1.03 and K_A = 1.78 × 10³ M^-1) at body temperature. Moreover, the structure of APOA-I was significantly altered in the presence of HES 130/0.4. Blood Ca²⁺ and Fe³⁺ will diminish the storage duration. The study provides accurate and thorough foundational data to clarify the binding mechanisms of HES 130/0.4 with APOA-I in vitro, which may help the comprehension of its impact on protein function and toxic mechanism during transit and distribution in the bloodstream.

Keywords: Apolipoprotein; Hydroxyethyl starch 130/0.4; Spectroscopy.