The Effect of Sulfur-Containing Compounds on the Quinoid Process of Adrenaline Autoxidation; Potential Neuroprotectors

摘要

The superoxide-generating reaction of adrenaline autoxidation in an alkaline medium, used in vitro to identify the antioxidant properties of various compounds, simulates the complex multistep process of quinoid oxidation of catecholamines (CA) in the body. Sulfur-containing cysteine (Cys) and reduced glutathione (GSH), as well as oxidized glutathione (GSSG), have been shown to inhibit this process. The studied substances considered as inhibitors of quinoid oxidation have been also evaluated as antioxidants. The IC50 values for Cys and GSH were close to 7.5 mu M. Inhibition by GSSG was weaker and represented approximately 50-70% of Cys and GSH inhibitory activity. The other sulfur-containing compounds that differ in chemical structure, the amino acids taurine and methionine were ineffective. The interest in this model and the search for effective compounds acting on this reaction is associated with one of the mechanisms of the etiopathogenesis of Parkinson's disease (PD) discussed in the literature; it is related to impairments of biochemical transformations of dopamine, particularly its quinoid oxidation. Cys, GSH and GSSG in the model system inhibit quinoid oxidation of adrenaline as well as inhibition of superoxide () formation. Experiments with the superoxide-generating enzymatic reaction of xanthine and xanthine oxidase, which chemistry is different and not related to the formation of quinoid metabolites, showed that the studied substances did not inhibit formation in this model. Thus, in this study we have shown that the biologically active sulfur-containing compounds Cys, GSH, and GSSG are specific inhibitors of quinoid oxidation of CA; it is likely that they may act as neuroprotectors. It is suggested that these compounds may be useful in the treatment and prevention of PD by activating their biosynthesis in the body.