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

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.

Synthesis, Structure and Impact of 5-Aminoorotic Acid and Its Complexes with Lanthanum(III) and Gallium(III) on the Activity of Xanthine Oxidase

“…In summary, Figures 2-4 show that all three compounds behave as scavengers of superoxide radicals, generated in the presence of the KO 2 and X/XO model systems in a concentration-dependent manner. The relative differences between the superoxidescavenging activities of these compounds were in agreement with their previously observed affinity to participate in interactions with stable free radicals via electron transfer reactions [54,55].…”

“…In order to elaborate on the possible reasons for the differing results when comparing scavenging of “non-enzymatic” superoxide KO 2 to that of “enzymatic” X/XO, a brief review of previously published results [ 54 , 55 ] is provided. The radical-scavenging activity of a compound is illustrated by the CL-SI calculated after the LDCL experiments.…”

“…A number of complexes of gallium (Ga) and lanthanum (La) have been investigated in recent years for their pharmacological activities [ 46 , 47 , 48 , 49 , 50 ]. The Ga(III) and La(III) complexes with 5-aminoorotic acid have been shown to be stronger in vitro antioxidants, compared to the free ligand, at a normal, homeostatic pH [ 51 , 52 , 53 , 54 ].…”

“…In our previous investigations, we observed differing in vitro interactions of 5-aminoorotic acid and its complexes with superoxide, generated by different model systems [ 54 , 55 ]. Possible interactions of the compounds investigated with components of the superoxide-generating model systems were proposed.…”

Content of sialic acids, ATP and superoxide anion-radical in loach embryos under the influence of flurenizyd

“…Супероксидний аніон-радикал утворюється як побічний продукт під час роботи дихального ланцюга мітохондрій [2, 17,19]. Також може утворюватися під час роботи інших ферментів (НАДН-дегідрогенази, ксантиноксидази) [20,25,27].…”