chiniofon and Hemolysis

7-Chloro-4-hydroxyquinoline (CQ) is an antitumor drug but its efficiency is not very satisfactory. This fact motivates us to study the relationship between the structure of 4-hydroxyquinoline with various substituent and its antioxidant effect against free-radical-initiated peroxidation: the hemolysis of human erythrocyte initiated thermally by water-soluble initiator, 2,2'-azobis (2-amidinopropane hydrochloride) (AAPH), acts as an experimental system. 7-Fluoro-4-hydroxyquinoline (FQ) and CQ can be synthesized by decarboxylation of 7-fluoro-4-hydroxyquinoline-3-carboxylic acid (FQCA) and 7-chloro-4-hydroxyquinoline-3-carboxylic acid (CQCA), respectively, and FQCA and CQCA are prepared by hydrolysis of ethyl 7-fluoro-4-hydroxyquinoline-3-carboxylate (FQCE) and ethyl 7-chloro-4-hydroxyquinoline-3-carboxylate (CQCE), respectively. The inhibitory concentration of 50% inhibition (IC(50)) of AAPH-induced hemolysis of the erythrocyte has been studied and found that all these chemicals dissolved in dimethyl sulfoxide (DMSO) can inhibit the free-radical-induced peroxidation. To clarify the relationship between the distributive status of the chemicals and their antioxidant effect, the chemical has been dissolved in the vesicle of dipalmitoyl phosphatidylcholine (DPPC) by sonication and suspended in the reaction system. It is found that FQCE, CQCE, FQCA and CQCA act as prooxidants either used alone or used in combination with alpha-tocopherol (TOH), demonstrating that FQCE, CQCE, FQCA and CQCA play a prooxidative role when they are packaged in the DPPC vesicle. This can be understood that the electron-attracting group, i.e. -COOC(2)H(5), -COOH, at the ortho position to the hydroxy group of quinoline makes the phenoxy radical of quinoline derivatives active by attracting negative charge from the electron-deficient radical site. These unstable free radicals preserved in DPPC vesicle can initiate additional propagation of lipid peroxidation and cause hemolysis. However, FQ and CQ without electron-attracting group are antioxidants even in DPPC vesicle either used alone, or mixed with TOH. Moreover, the antioxidative activity of FQ is much better than CQ either used alone or in combination with TOH, indicating that FQ has the potential to replace CQ to be an antioxidant drug. Therefore, the antioxidant/prooxidant effect is not only correlated with the molecular structure but also the distributive status in the reaction system.

Topics: 1,2-Dipalmitoylphosphatidylcholine; alpha-Tocopherol; Amidines; Antioxidants; Erythrocytes; Free Radicals; Hemolysis; Humans; Hydroxyquinolines; Models, Chemical; Oxidants; Time Factors

The effects of quartz and sodium metasilicate on liposomes were studied in order to understand the mechanism of silicosis. 8-Hydroxyquinoline-5-sulfonic acid was tested for its in situ silicosis-prevention capacity. Two types of liposomes--(A) those incorporating cholesterol and (B) those without cholesterol--were used. The tests consisted of measuring permeability changes caused by the above-mentioned chemicals. Permeabilities were found to depend on membrane composition. Tests on quartz action led us to the conclusion that liposomes of this composition did not simulate the erythrocytes very well. It was also observed that absence or presence of cholesterol and the mode of contact altered the effect of quartz. Silicate destabilized type A liposomes, but this was less than that caused by quartz. This was explained by the concentration of monosilicic acid that dissolves out from quartz and silicate. When quartz was pretreated with the preventive, the type A liposomes were stabilized, but a slight destabilizing effect was observed on type B. 8-Hydroxyquinoline-5-sulfonic acid augmented the destabilizing effect of silicate, whereas it decreased the hemolytic activity of uncoated quartz, indicating a preventive potential in in vivo.

Topics: Animals; Chelating Agents; Chromates; Erythrocytes; Hemolysis; Hydroxyquinolines; In Vitro Techniques; Liposomes; Oxyquinoline; Quartz; Sheep; Silicates; Silicic Acid; Silicosis