nitroarginine and Glioma

The present study was undertaken to examine the role of reactive oxygen species (ROS) and glutathione (GSH) in glia cells using human glioma cell line A172 cells. HgCl2 caused the loss of cell viability in a dose-dependent manner. HgCl2-induced loss of cell viability was not affected by H2O2 scavengers catalase and pyruvate, a superoxide scavenger superoxide dismutase, a peroxynitrite scavenger uric acid, and an inhibitor of nitric oxide N(G)-nitro-arginine Methyl ester. HgCl2 did not cause changes in DCF fluorescence, an H2O2-sensitive fluorescent dye. The loss of cell viability was significantly prevented by the hydroxyl radical scavengers dimethylthiourea and thiourea, but it was not affected by antioxidants DPPD and Trlox. HgCl2-induced loss of cell viability was accompanied by a significant reduction in GSH content. The GSH depletion was almost completely prevented by thiols dithiothreitol and GSH, whereas the loss of viability was partially prevented by these agents. Incubation of cells with 0.2 mM buthionine sulfoximine for 24 hr, a selective inhibitor of gamma-glutamylcysteine synthetase, resulted in 56% reduction in GSH content without any change in cell viability. HgCl2 resulted in 34% reduction in GSH content, which was accompanied by 59% loss of cell viability. These results suggest that HgCl2-induced cell death is not associated with generation of H2O2 and ROS-induced lipid peroxidation. In addition, these data suggest that the depletion of endogenous GSH itself may not play a critical role in the HgCl2-induced cytotoxicity in human glioma cells.

Topics: Brain Neoplasms; Buthionine Sulfoximine; Cell Survival; Fluorescent Dyes; Free Radical Scavengers; Glioma; Glutathione; Humans; Kinetics; Mercuric Chloride; Nitroarginine; Reactive Oxygen Species; Spectrometry, Fluorescence; Tumor Cells, Cultured; Uric Acid

We studied the effects of NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine (L-NNA) on the selective ATP and adenosine-induced enhancement of intratumoral blood flow in rats measured by the hydrogen clearance method. Both adenosine and ATP produced a selective enhancement of the intratumoral blood flow. Neither L-NMMA nor L-NNA had a significant effect on either the CBF or the intratumoral blood flow. Adenosine-induced enhancement was not inhibited by L-NMMA or L-NNA. On the other hand, the ATP-induced enhancement was totally inhibited by both L-NMMA and L-NNA. The inhibitory action of L-NMMA against ATP was blocked by L-arginine, but not by D-arginine. It is suggested that the ATP-induced increase of intratumoral blood flow is evoked by nitric oxide synthesized from the endothelium of the intratumoral blood vessels.

Topics: Adenosine; Adenosine Triphosphate; Animals; Arginine; Brain Neoplasms; Glioma; Male; Nitroarginine; omega-N-Methylarginine; Rats; Rats, Inbred Strains; Regional Blood Flow; Tumor Cells, Cultured