Toxicity of thimerosal in biological systems: Conformational changes in human hemoglobin, decrease of oxygen binding capacity, increase of protein glycation and amyloid's formation

• Published in: International journal of biological macromolecules Vol. 154; pp. 661 - 671
• Main Authors: de Magalhães Silva, Marina, de Araújo Dantas, Maria Dayanne, da Silva Filho, Reginaldo Correia, dos Santos Sales, Marcos Vinicius, de Almeida Xavier, Jadriane, Leite, Ana Catarina Rezende, Goulart, Marília Oliveira Fonseca, Grillo, Luciano Aparecido Meireles, de Barros, Wellington Alves, de Fátima, Ângelo, Figueiredo, Isis Martins, Santos, Josué Carinhanha Caldas
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2020
• Subjects: Advanced glycation end products; Amyloid beta-Peptides - metabolism; Glycation End Products, Advanced - metabolism; Hemoglobins - metabolism; Humans; Oxygen - metabolism; Preservatives, Pharmaceutical - toxicity; Red cells and human erythrocytes; Thimerosal - toxicity; Vaccines and cosmetics; Red cells and human erythrocytes; Advanced glycation end products; Vaccines and cosmetics
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.03.156

Thimerosal (TH), an organomercurial compound, is used as a preservative in vaccines and cosmetics. Its interaction with human hemoglobin (Hb) was investigated under physiological conditions using biophysical and biological assays, aiming to evaluate hazardous effects. TH interacts spontaneously with Hb (stoichiometry 2:1, ligand-protein), preferably by electrostatic forces, with a binding constant of 1.41 × 106 M−1. Spectroscopic data allows to proposing that TH induces structural changes in Hg, through ethylmercury transfer to human Hb-Cys93 residues, forming thiosalicylic acid, which, in turn, interacts with the positive side of the amino acid in the Hb-HgEt adduct chain. As a consequence, inhibition of Hb-O2 binding capacity up to 72% (human Hb), and 50% (human erythrocytes), was verified. Dose-dependent induction of TH forming advanced glycation end products (AGE) and protein aggregates (amyloids) was additionally observed. Finally, these results highlight the toxic potential of the use of TH in biological systems, with a consequent risk to human health.
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•Thimerosal interacts with hemoglobin, leading to structural conformation changes.•Hb-Cys93 residues are blocked by ethylmercury transferred from thimerosal.•Thimerosal decreases Hb-O2 binding capacity by up to 72% at physiological conditions.•Thimerosal induces protein glycation and amyloid formation in human hemoglobin.