darinaparsin and dimethylarsinous-acid

Surface enhanced Raman scattering (SERS) has great potential as an alternative tool for arsenic speciation in biological matrices. SERS measurements have advantages over other techniques due to its ability to maintain the integrity of arsenic species and its minimal requirements for sample preparation. Up to now, very few Raman spectra of arsenic compounds have been reported. This is particularly true for thiolated arsenicals, which have recently been found to be widely present in humans. The lack of data for Raman spectra in arsenic speciation hampers the development of new tools using SERS. Herein, we report the results of a study combining the analysis of experimental Raman spectra with that obtained from density functional calculations for some important arsenic metabolites. The results were obtained with a hybrid functional B3LYP approach using different basis sets to calculate Raman spectra of the selected arsenicals. By comparing experimental and calculated spectra of dimethylarsinic acid (DMA

Topics: Arsenicals; Cacodylic Acid; Glutathione; Organometallic Compounds; Quantum Theory; Solutions; Spectrum Analysis, Raman; Vibration; Water

Although inorganic arsenite (As(III)) is toxic in humans, it has recently emerged as an effective chemotherapeutic agent for acute promyelocytic leukemia (APL). In humans and most animals, As(III) is enzymatically methylated in the liver to weakly toxic dimethylarsinic acid (DMAs(V)) that is a major pentavalent methylarsenic metabolite. Recent reports have indicated that trivalent methylarsenicals are produced through methylation of As(III) and participate in arsenic poisoning. Trivalent methylarsenicals may be generated as arsenical-glutathione conjugates, such as dimethylarsinous glutathione (DMAs(III)G), during the methylation process. However, less information is available on the cytotoxicity of DMAs(III)G.. We synthesized and purified DMAs(III)G using high performance TLC (HPTLC) methods and measured its cytotoxicity in rat liver cell line (TRL 1215 cells).. DMAs(III)G was highly cytotoxic in TRL 1215 cells with a LC(50) of 160 nM. We also found that DMAs(III)G molecule itself was not transported efficiently into the cells and was not cytotoxic; however it readily became strongly cytotoxic by dissociating into trivalent dimethylarsenicals and glutathione (GSH). The addition of GSH in micromolar physiological concentrations prevented the breakdown of DMAs(III)G, and the DMAs(III)G-induced cytotoxicity. Physiological concentrations of normal human serum (HS), human serum albumin (HSA), and human red blood cells (HRBC) also reduced both the cytotoxicity and cellular arsenic uptake induced by exposure to DMAs(III)G.. These findings suggest that the significant cytotoxicity induced by DMAs(III)G may not be seen in healthy humans, even if DMAs(III)G is formed in the body from As(III).

Topics: Animals; Antineoplastic Agents; Arsenic Poisoning; Arsenicals; Arsenites; Cacodylic Acid; Cell Line; Cell Survival; Chromatography, Thin Layer; Dose-Response Relationship, Drug; Erythrocytes; Glutathione; Hepatocytes; Humans; Inhibitory Concentration 50; Methylation; Rats; Rats, Inbred F344; Serum Albumin; Time Factors