[Alcohol and free oxygen radicals]. / Alcool e radicais livres de oxigénio.

Oxygen free radicals may be generated during ethanol metabolization by cytochrome P450, or due to the formation of xanthine oxidase by ethanol effect on xanthine dehydrogenase. After transformation into acetaldehyde, the metabolism of this compound by xanthine oxidase or by aldehyde oxidase also generates oxygen radicals. We present the hypothesis of a vicious cycle during ethanol metabolization by aldehyde oxidase, which would amplify the process and be responsible for an increased degree of lipid peroxidation.

Angiotensin converting enzyme inhibitors as oxygen free radical scavengers.

The authors have compared the ability of two non-SH-containing angiotensin converting enzyme (ACE) inhibitors (enalaprilat and lisinopril) with an -SH containing ACE inhibitor (captopril) to scavenge the hydroxyl radical (.OH). All three compounds were able to scavenge .OH radicals generated in free solution at approximately diffusion-controlled rates (10(10) M-1 s-1) as established by the deoxyribose assay in the presence of EDTA. The compounds also inhibited deoxyribose degradation in reaction mixtures which did not contain EDTA but not so effectively. This later findings also suggests that they have some degree of metal-binding capability. Chemiluminescence assays of oxidation of hypoxanthine by xanthine oxidase in the presence of luminol, confirm that the three ACE inhibitors are oxygen free radical scavengers. Our results indicate that the presence of a sulphydryl group in the chemical structure of ACE inhibitors is not relevant for their oxygen free radical scavenging ability.

[Angiotensin-converting enzyme inhibitors as neutralizers of hydroxyl radical]. / Inibidores do enzima conversor da angiotensina como neutralizadores do radical hidroxilo.

Angiotensin converting enzyme inhibitors are utilized in the treatment of essential hypertension and of chronic cardiac failure. They are also employed in the treatment of the myocardial lesion of ischemia-reperfusion, which involves oxygen free radicals. In the present study we investigated the possibility of three angiotensin converting enzyme inhibitors (captopril, enalapril, lisinopril) to act as hydroxyl radical scavengers. The rate constants for reactions of those compounds with .OH were determined using the deoxyribose method. All there compounds proved to be good scavengers of .OH with rate constants of about 10(10)M-1s-1 and are iron chelators specially enalapril. The fact that captopril possesses a thiol group does not confer an higher antioxidative capacity. These results suggest that scavenging of oxygen free radicals may be a possible mechanism contributing to the therapeutic effect of angiotensin converting enzyme inhibitors.

Oxidative inhibition of red blood cell ATPases by glyceraldehyde.

Glyceraldehyde and other simple monosaccharides autoxidize under physiological conditions, forming dicarbonyl compounds and hydrogen peroxide via intermediate free radicals. These products may have deleterious effects on cell components. In this paper we study the effect of glyceraldehyde autoxidation on red-cell ATPase activities. The autoxidation of glyceraldehyde in imidazole-glycylglycine buffer, measured by oxygen consumption, depends on the buffer concentration and decreases in the presence of superoxide dismutase and catalase. The addition of DETAPAC inhibits the autoxidation almost completely. When human red-blood-cell membranes are incubated with glyceraldehyde, the red-blood-cell ATPase activities decrease significantly. The addition of DETAPAC, GSH and DTE (dithioerythritol) protects the enzyme from inactivation, but superoxide dismutase and catalase have no effect. Methylglyoxal (a dicarbonyl which is analogous to hydroxypyruvaldehyde derived from glyceraldehyde autoxidation) proved to have a powerful inhibitory action on ATPase activities. The addition of DTE completely protects the enzyme from inactivation, suggesting that the sulphydryl groups of the active site of the enzyme are the critical targets for dicarbonyl compounds.

Mechanisms of hemolysis induced by copper.

An excess of copper is the cause of hemolysis in a number of clinical conditions. Incubation of human erythrocyte (RBC) suspensions with copper (II) causes the formation of methemoglobin, lipid peroxidation and hemolysis. A new variant of the thiobarbituric acid (TBA) method, which minimizes the formation of interfering chromophores, was used to detect lipid peroxidation. Lipid peroxidation precedes hemolysis and the antioxidant vitamins C and E, which inhibit lipid peroxidation, also inhibit hemolysis. Consequently lipid peroxidation appears to be the cause of RBC destruction. Lipid peroxidation arises mostly from the oxidation of oxyhemoglobin by copper as it is inhibited in RBCs with carbon monoxyhemoglobin or methemoglobin. A direct interaction of copper with the red cell membrane seems to play only a minor role. Copper effects depend on the presence of free SH groups. Lipid peroxidation is probably initiated by activated forms of oxygen as it is increased by an inhibitor of catalase and reduced by hydroxyl radical scavengers. With higher copper concentrations hemolysis is greater: its mechanism appears different as lipid peroxidation is smaller but hemoglobin alterations, namely precipitation, are more pronounced.

Mannose inhibition as a significant marker for differentiating among novobiocin-resistant staphylococci of relevance in clinical microbiology.

A specific method for the identification of Staphylococcus saprophyticus among novobiocin-resistant species isolated from man is described. The test is based on novobiocin resistance, non-fermentation of D-mannose and early inhibition with late secondary growth on glucose/mannose + novobiocin agar plates. On this medium novobiocin-resistant Staphylococcus cohnii showed a confluent, continuous and homogeneous growth after 24 h which remained unchanged at 48 h whether or not it fermented D-mannose, whereas novobiocin-resistant Staphylococcus xylosus fermented D-mannose. These results are discussed in relation to a possible causal role of PTS enzymes and phosphomannose isomerase deficiency in mannose inhibition.

The neutralization of hydroxyl radical by silibin, sorbinil and bendazac.

The compounds silibin, sorbinil and bendazac act as hydroxyl radical scavengers, when the hydroxyl radical is generated by the Fenton reaction. Hydroxyl was detected by the degradation of deoxyribose. The Authors discuss the possibility that the scavenger activities of those compounds may explain, at least in part, their therapeutic activity.