Lanthanum, Gallium and their Impact on Oxidative Stress

Abstract

The role metals play in living organisms is well established and subject to extensive research. Some of them participate in electron-exchange reactions. Such reactions cause generation of free radicals that can adversely impact biological systems, as a result of oxidative stress. The impact of ‘non-biological’ metals on oxidative stress is also a worthy pursuit due to the crucial role they play in modern civilization. Lanthanides (Ln) are widely used in modern technology. As a result, human exposure to them is increasing. They have a number of established medical applications and are being extensively researched for their potential antiviral, anticancer and anti-inflammatory properties. The present review focuses on lanthanum (La) and its impact on oxidative stress. Another metal, widely used in modern high-tech is gallium (Ga). In some respects, it shows certain similarities to La, therefore it is a subject of the present review as well. Both metals exhibit ionic mimicry which allows them to specifically target malignant cells, initiating apoptosis that makes their simple salts and coordination complexes promising candidates for future anticancer agents.

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

“…If the anticancer agent eliminates the O 2 •− at pH of 7.45, this protects healthy cells from malignization. Ga(III)-containing compounds are promising anticancer agents [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], the metal ion being responsible for the toxicity against malignant cells [ 24 , 25 , 26 , 27 ]. The Ga(III) complex of 5-aminoorotic acid proved to be a better antioxidant than the ligand itself at normal homeostatic pH [ 39 , 40 ], but its interaction with O 2 •− at this pH was not elucidated.…”

“…Since cancer cells require iron in larger quantities, compared to normal cells [ 24 ], the introduction of Ga(III) in order to disrupt the iron-dependent metabolic pathways [ 25 ] in malignant cells seems a promising strategy in cancer treatment [ 26 ]. Ga(III) salts are well known anticancer agents [ 27 , 28 ]. Simple gallium salts such as gallium nitrate, gallium chloride, and gallium citrate have been investigated for their antitumor, anti-inflammatory, and antimicrobial properties [ 29 ].…”

“…The interaction of HAOA and gallium(III) 5-aminoorotate (GaAOA) with superoxide radical has still not been investigated. Generally, little investigation on the impact gallium substances have on oxidative stress has been carried out so far [ 28 ]. Increasing human exposure to that metal, resulting most prominently from technogenic pollution, makes that a subject of rising importance from the viewpoint of the authors of the present research paper.…”

Effects of Rare Earth Elements on Blood Pressure and Their Exposure Biomarkers: Evidence from Animal Experiments

“…A number of REE elements play a role in the electron-exchange reactions in living organisms, causing the generation of free radicals that affect biological processes, e.g., oxidative stress [ 29 ]. In the previous study, it was demonstrated that REEs had a hormetic effect on oxidative stress.…”

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

“…Successful transport of lanthanide ions to the tumor has to be accompanied by some kind of mechanism to avoid their detrimental effect on healthy cells. These somewhat contradicting requirements characterize the search for new coordination compounds with improved antitumor activity and protective effects on normal cells [ 44 , 45 ]. One possible solution would be to use a coordination complex, comprising a highly pro-oxidant lanthanide cation, surrounded by bioactive ligands with antioxidant capacity.…”