Phenylmercury induces structural and functional alterations on hemoglobin: From isolated protein to a biological...

Contamination by potentially toxic metals, such as mercury (Hg) and its derivatives, poses a serious risk to human health and the environment. Phenylmercury (PM) is an organometallic compound used as a fungicide, the toxicity of which has been little explored. This study investigated the effects of PM at three levels of complexity: protein (human hemoglobin [Hb]), cell (human erythrocytes [Ery]), and animal (zebrafish [Danio rerio]). Theoretical and biophysical studies indicated that PM interacts with the heme group and cysteine residues of Hb, with a binding constant (Kb) of 1.47(± 0.22)× 10⁴ M⁻¹ , suggesting the formation of a stable Hb-PM complex. The PM capacity to bind Hb cysteines, changes to the Soret band, and reduced protein electrophoretic mobility. In Ery exposed to PM (0.125-1.0 μM), oxygen uptake was reduced by 48%. The production of reactive oxygen species (ROS) increased 2.2-fold, with a 2-fold increase in H₂O₂ levels and a 90% increase in •NO production. Catalase and glutathione peroxidase activities decreased by 25% and 49%, respectively, while superoxide dismutase increased by 13%. The GSH/GSSG ratio and total sulfhydryl group content concentration in 34% and 44%, respectively, while carbonylated content increased 2.2-fold. PM caused structural changes in the Ery membrane, morphology, and elasticity. Finally, in vivo zebrafish assays demonstrated that PM has teratogenic effects and reduced heart rate. Therefore, PM exhibits toxicity at the three complexity levels evaluated: it compromises the structure and function of Hb and the redox system of Ery and causes marked changes in zebrafish development.