ABSTRACT
Some antioxidant compounds have a pro-oxidant effect in the presence of transition metal ions, due to the reduction of Mn+ to M(n-1)+ with simultaneous formation of free radicals, which then promote DNA damage. In the present study, we evaluated the pUC19 DNA damage in a solution containing Cu(II) and ascorbic acid (AA) or S(IV) saturated with air by agarose gel electrophoresis. Our results showed that this damage decreases if AA and S(IV) are simultaneously added. This study also illustrates the importance of Cu(II) in this process, as no DNA damage was observed when AA or S(IV) were present in the absence of this metallic ion. Our data showed that DNA preservation depends on the concentration of AA and S(IV) and occurs when the [S(IV)]:[AA] ratio ranges from 1:1 to 20:1. Absorbance measurements and thermodynamic data show that no reaction occurs between AA and S(IV) when this mixture (pH 5.5) is added to pUC-19 DNA. The presence of dissolved oxygen may be the cause of AA consumption in the mixture of these two antioxidants, which subsequently decreases DNA damage.
Subject(s)
Ascorbic Acid/adverse effects , Sulfites , DNA Damage , Copper/pharmacology , Ions/adverse effects , Antioxidants/adverse effects , Electrophoresis, Agar Gel/instrumentation , Free Radicals/pharmacology , Hydrogen-Ion ConcentrationABSTRACT
Drugs bearing metal-coordinating moieties can alter biological metal distribution. In this work, a complex between iron(II) and diflunisal was prepared in the solid state, exhibiting the following composition: [Fe(diflunisal)2(H2O)2], (Fe(dif)2). The ability of diflunisal to alter labile pools of both plasmatic and cellular iron was investigated in this work. We found out that diflunisal does not increase the levels of redox-active iron in plasma of iron overloaded patients. However, diflunisal efficiently carries iron into HeLa or HepG2 cells, inducing an iron-catalyzed oxidative stress.
Subject(s)
Coordination Complexes/chemical synthesis , Ferrous Compounds/chemistry , Iron/chemistry , Sulfides/chemistry , Catalysis , Coordination Complexes/chemistry , Ferrous Compounds/pharmacokinetics , HeLa Cells , Hep G2 Cells , Humans , Molecular Structure , Oxidative Stress , Tumor Cells, CulturedABSTRACT
Iron acquisition by bacteria and fungi involves in several cases the promiscuous usage of siderophores. Thus, antibiotic resistance from these microorganisms can be circumvented through a strategy of loading toxic metals into siderophores (Trojan Horse Effect). Desferrioxamine (dfo) and its cell-permeant derivative desferrioxamine-caffeine (dfcaf) were complexed with aluminum or gallium for this purpose. The complexes Me(dfo) and Me(dfcaf) (Me=Al3+ and Ga3+) were synthesized and characterized by mass spectroscopy and cyclic voltammetry. Their relative stabilities were studied through competitive equilibria with fluorescent probes calcein, fluorescein-desferrioxamine and 8-hydroxyquinoline. Me(dfo) and Me(dfcaf) were consistently more toxic than free Me3+ against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans, demonstrating the Trojan Horse Effect. Wide spectrum antimicrobial action can be obtained by loading non-essential or toxic metal ions to microbes via a convenient siderophore carrier.
