Scavenging of reactive species probed by EPR and ex-vivo nanomolar reduction of lipid peroxidation of manganese complexes

Abstract

Antioxidant activity toward H2O2, anion radical superoxide, hydroxyl and DPPH (2,2-diphenyl-1-picrylhydrazyl) of two manganese complexes [Mn(III)(bpa)2]Cl.H2O (1) and [(Cl)Mn(μ-hbpclnol)(μ-bpclnol)Mn](ClO4).3H2O (2) (hbpa = (2-hydroxybenzyl-2-pyridylmethyl)amine and h2bpclnol = (N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)[(3-chloro)(2-hydroxy)]propylamine) are presented. X-ray diffraction studies were performed for complex (1). Both complexes presented similar or better activities than reference complex [Mn(salen)Cl], when the interaction between them and ROS (H2O2, O2•- and •OH), was monitored, by EPR (Electron Paramagnetic Resonance), in PBS, DMSO and water. The antioxidant activity rank of complexes toward •OH, generated by Fenton reaction and monitored by EPR, is (2) > (1) > [Mn(salen)Cl], in water (0.1% of DMSO for each complex), with the values of the IC50 of 7.2 (±1.6), 15.5 (±1.8) and 29.1 (±2.01) μM respectively. EPR data presented herein suggest that complex (2) presents the better scavenging activity toward hydroxyl, being in good agreement with TBARS assay results, in which complex (2) presented the best inhibitory activity toward lipid peroxidation, employing Swiss mice liver homogenate tissue model. IC50 values obtained from the interaction between these complexes and hydroxyl, using TBARS method, were: 0.88 (± 0.029); 0.73 (± 0.01) and 42.7 (± 3.5) nM, respectively for (1), (2) and [Mn(salen)Cl]. Complexes (1) and (2) are regulating the lipid homeostasis, protecting the tissue from the lipid peroxidation, in nanomolar scale, motivating in vivo studies. Redox properties and radical scavenging activity of complexes toward DPPH are non-linear and solvent dependent. Furthermore, the monitoring of antioxidant activity probed by EPR could be a fair and appropriate study to guide more advanced investigations.