ascorbic-acid and cuprous-chloride

This study was undertaken to try to determine the possible anti-leishmanial activity of S2-Complex, an organic complex of copper chloride, ascorbic acid, and nicotinamide. The promastigotes, axenic amastigotes, and intracellular amastigotes of both Leishmania major and Leishmania tropica were incubated with different concentrations of S2-Complex. The EC50 for each form was calculated. Results show that all forms of the parasites were dose dependently inhibited by S2-Complex. The promastigotes of both parasites were the most resistant with highest EC50 followed by axenic amastigotes. While intracellular amastigotes were the most sensitive with the lowest EC50. These results indicate that S2-Complex has a direct anti-leishmanial effect. When mice were treated with S2-Complex or BCG for four days before harvesting the macrophages, and the macrophages infected with both L. major and L. tropica, they showed increased phagocytosis and increased parasite killing. The results of S2-Complex were not statistically different from the immunomodulating agent BCG. These results indicate that S2-Complex has an immunomodulating effect in addition to the direct anti-leishmanial effect.

Topics: Animals; Ascorbic Acid; BCG Vaccine; Copper; Culture Media; Drug Combinations; Immunologic Factors; Injections, Intraperitoneal; Leishmania major; Leishmania tropica; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Niacinamide; Starch

Previously, our laboratory (Li, S.; et al. Biochemistry 1995, 34, 5762-5772) showed that the oxidation of recombinant human relaxin (Rix) could be induced by ascorbic acid (AsA)/Cu(II), a system used for the metal-catalyzed generation of reactive oxygen species. In this study, we observed that this oxidation could be inhibited by high concentrations of mannitol and other sugars and polyols, such as ethylene glycol, glycerol, glucose, and dextran. Similar protective effects with high concentrations of mannitol were also observed in the AsA/CuCl2-induced oxidation of Gly-Met-Gly and Gly-His-Gly. In contrast, (carboxymethyl)cellulose had no protective effect on the metal-catalyzed oxidation of Rix. These results, together with results from deuterium isotope experiments and spectroscopic experiments, suggest that the inhibitory effect of polyols and sugars is probably due to the complexation of transition metal ions rather than a hydroxyl radical scavenging mechanism. However, dextran, a high molecular weight polysaccharide, might function as a hydroxyl radical scavenger to protect Rix from the metal-catalyzed oxidation.

Topics: Ascorbic Acid; Carbohydrates; Copper; Humans; Kinetics; Metals; Oligopeptides; Oxidation-Reduction; Polymers; Relaxin; Spectrophotometry, Ultraviolet