In Vitro Interaction of 5-Aminoorotic Acid and Its Gallium(III) Complex with Superoxide Radical, Generated by Two Model Systems.

Lozan Todorov,Maria Traykova,Luciano Saso,Irena Kostova

doi:10.3390/ijms21228862

Lozan Todorov, Maria Traykova + Show 2 more

Open Access

https://doi.org/10.3390/ijms21228862

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Abstract

Increased levels of the superoxide radical are associated with oxidative damage to healthy tissues and with elimination of malignant cells in a living body. It is desirable that a chemotherapeutic combines pro-oxidant behavior around and inside tumors with antioxidant action near healthy cells. A complex consisting of a pro-oxidant cation and antioxidant ligands could be a potential anticancer agent. Ga(III) salts are known anticancer substances, and 5-aminoorotic acid (HAOA) is a ligand with antioxidant properties. The in vitro effects of HAOA and its complex with Ga(III) (gallium(III) 5-aminoorotate (GaAOA)) on the in vitro accumulation of superoxide and other free radicals were estimated. Model systems such as potassium superoxide (KO2), xanthine/xanthine oxidase (X/XO), and rat blood serum were utilized. Data suggested better antioxidant effect of GaAOA compared to HAOA. Evidently, all three ligands of GaAOA participated in the scavenging of superoxide. The effects in rat blood serum were more nuanced, considering the chemical and biochemical complexity of this model system. It was observed that the free-radical-scavenging action of both compounds investigated may be manifested via both hydrogen donation and electron transfer pathways. It was proposed that the radical-scavenging activities (RSAs) of HAOA and its complex with Ga(III) may be due to a complex process, depending on the concentration, and on the environment, nature, and size of the free radical. The electron transfer pathway was considered as more probable in comparison to hydrogen donation in the scavenging of superoxide by 5-aminoorotic acid and its gallium(III) complex.

Highlights

The superoxide radical (O2−) is involved in many normal and pathological bio-reactions in the living body [1]
The complexity of the content of the environment imposes a risk of various effects on the radical-scavenging activity of HAOA and gallium(III) 5-aminoorotate (GaAOA). Both 5-aminoorotic acid and its complex with Ga(III) may exhibit antioxidant action via hydrogen donation and electron transfer, the former being more probable in the presence of HAOA and the latter being more evident in the presence of GaAOA
(4) The electron transfer pathway was considered more probable than hydrogen donation in the scavenging of superoxide by the gallium(III) complex. 5-Aminoorotic acid seems to manifest its antioxidant action via both pathways

Summary

Introduction

The superoxide radical (O2−) is involved in many normal and pathological bio-reactions in the living body [1]. Our investigation proved that both HAOA and GaAOA were scavengers of the superoxide radical at normal physiological pH (7.45) It suggested that in healthy tissues these compounds act as antioxidants, eliminating superoxide, thereby preventing oxidative cellular damage. Both 5-aminoorotic acid and its complex with Ga(III) may exhibit antioxidant action via hydrogen donation and electron transfer, the former being more probable in the presence of HAOA and the latter being more evident in the presence of GaAOA

Materials and Methods

Assay for CL in the Presence of KO2

Trolox Equivalent Calculations

Findings

Conclusions