David Jay

Superoxide dismutase activity of the captopril-iron complex

With an assay that generates superoxide anion radicals without the intervention of metal ions we investigated the antioxidant properties of captopril, an angiotensin-converting enzyme inhibitor with a sulfhydryl group. Under these conditions, increasing concentrations of the drug were seen not to scavenge O·2− directly. However, a combination of captopril and iron could bring about the breakdown of the superoxide anion; a result that may help to understand the free radical-scavenging properties of captopril.

Superoxide Dismutase Activity of the Salicylate-Iron Complex

BACKGROUND Scavenging of superoxide radical by salicylate-iron complex was studied to determine whether or not the salicylate-iron complex was able to catalyze the dismutation of superoxide radicals, the result perhaps yielding an explanation of the antioxidant and anti-inflammatory properties of the drug. METHODS The scavenging was studied with an assay that generates O2.- without the intervention of metal ions. RESULTS Results indicated that, in the presence of iron, salicylate was able to bring about the catalytic dismutation of the superoxide radical. The rate of superoxide removal was dependent on both the concentration of iron and the salicylate:iron molar ratio. CONCLUSIONS These results may help to explain the interaction of nonsteroidal anti-inflammatory drugs with free radicals and the anti-inflammatory properties of these agents, inasmuch as accumulating evidence indicates that much of the injury observed during inflammatory disorders may be mediated by oxidative stress frequently induced by iron-dependent reactions.

Study of a Fenton type reaction: effect of captopril and chelating reagents.

The purpose of this study was to determine if captopril, an angiotensin-converting enzyme inhibitor, could interact with iron ions and so modify a Fenton type reaction. Results indicate that different degrees of thiobarbituric acid-reactive substance from deoxyribose are obtained in an ascorbate-driven Fenton system depending on the order of addition of captopril and iron to the incubation medium. Similar results were obtained with the chelating reagents ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid, indicating that the buffer solution plays a relevant role when a particular iron complex is formed with a chelating agent. These metal complexes produce oxidizing species in a Fenton type system whose nature is discussed.

Superoxide-Superoxide Oxidoreductase Activity of the Captopril-Copper Complex

BACKGROUND The purpose of this study was to determine whether the interaction of captopril, an angiotensin-converting enzyme inhibitor, with copper could modify the superoxide dismutase activity of this metal. Results may help to explain the interaction of captopril with reactive oxygen species in the stunned myocardium where substantial mobilization of copper and iron in the coronary flow following ischemia has been reported. METHODS An assay that generates superoxide anion radicals without the intervention of metal ions was utilized. In addition, direct EPR analysis was applied to assess the redox state of copper during reactions. RESULTS Captopril-copper complex inhibited the superoxide-mediated reduction of nitroblue tetrazolium. In addition, captopril-copper complex was able to suppress formazan production by potassium superoxide. Direct EPR analysis showed that copper was reduced to the cuprous state by captopril and remained in this state in the course of the reaction. Captopril was also stable during the dismutation reaction. CONCLUSIONS We conclude that cuprous-captopril complex is a catalytic species with properties different from those of Cu(2+) alone. A model in which sulfur acts as electron acceptor/donor in place of the metal is proposed and a mechanism of action for this complex is discussed.

Inhibition of membrane-bound succinate dehydrogenase by fluorescamine

Fluorescamine rapidly inactivated membrane-bound succinate dehydrogenase. The inhibition of the enzyme by this reagent was prevented by succinate and malonate, suggesting that the group modified by fluorescamine was located at the active site. The modification of the active site sulfhydryl group by 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB) did not alter the inhibitory action of fluorescamine. However, the protective effect of malonate against fluorescamine inhibition was abolished in the enzyme modified at the thiol.