lithium is a drug used for the treatment of bipolar disorder. it has several mechanisms of action, and recently it is shown that lithium can antagonize the 5-ht1b/1d serotonin receptors. sumatriptan is a 5-ht1b/1d receptor agonist used for the treatment of cluster headaches and migraine which might cause memory impairment as a potential side effect. in this study, effects of lithium on sumatrip...

In solid tumors, HIF1 upregulates the expression of hundreds of genes involved in cell survival, tumor growth, and adaptation to the hypoxic microenvironment. HIF1 stabilization and activity are suppressed by prolyl and asparagine hydroxylases, which require oxygen as a substrate and ascorbate as a cofactor. This has led us to hypothesize that intracellular ascorbate availability could modify t...

hormone-independent prostate cancer cell lines are resistant to antineoplastic drugs, this study sought to determine the usefulness of lithium chloride as an inhibitor of glycogen synthase kinase-3β to increase the cytotoxic effect of doxorubicin, etoposide or vinblastine antineoplastic drugs on du145 cells. combination effect was assessed by using low and ic50 doses of drugs + lithium chloride...

Intravenous application of high-dose ascorbate is used in complementary palliative medicine to treat cancer patients. Pharmacological doses of ascorbate in the mM range induce cytotoxicity in cancer cells mediated by reactive oxygen species (ROS), namely hydrogen peroxide and ascorbyl radicals. However, little is known about intrinsic or extrinsic factors modulating this ascorbate-mediated cyto...

Ascorbate reduces the oxidation rate of catecholamines and, by an independent mechanism, enhances rabbit aortic ring contractions initiated by catecholamines. The largest significantly different fractional increases in force produced by ascorbate enhancement of norepinephrine (NE), epinephrine, phenylpropanolamine (PPA), and ephedrine (Eph) are 5.5, 1.8, 1.6, and 1.3 times, respectively. In phy...

Sodium ascorbate (vitamin C) has a reputation for inconsistent effects upon malignant tumor cells, which vary from growth stimulation to apoptosis induction. Melanoma cells were found to be more susceptible to vitamin C toxicity than any other tumor cells. The present study has shown that sodium ascorbate decreases cellular iron uptake by melanoma cells in a dose- and time-dependent fashion, in...

These experiments examined the effects of pre-test intra dorsal hippocampus (intra-CA1) administration of GABAA receptor agonist and antagonist, muscimol and bicuculline respectively, on state-dependent learning induced by lithium. Male NMRI mice were trained in a one-trial step-down inhibitory avoidance task, and immediately after training they received IP injections of either saline (10 mL/kg...

Glutathione deficiency, induced in adult mice by administering buthionine sulfoximine (an inhibitor of glutathione synthesis), led to a rapid and substantial increase in ascorbate in the liver. This effect was apparent 2-4 hr after giving the inhibitor; subsequently, the level of ascorbate decreased and that of dehydroascorbate increased markedly, supporting the conclusion that glutathione func...

Erythrocytes can reduce extracellular ascorbate free radicals by a plasma membrane redox system using intracellular ascorbate as an electron donor. In order to test whether the redox system has electrogenic properties, we studied the effect of ascorbate free radical reduction on the membrane potential of the cells using the fluorescent dye 3,3'-dipropylthiadicarbocyanine iodide. It was found th...