ascorbic-acid and 2-thiomalic-acid

We previously showed that inhibition of catalase and glutathione peroxidase activities in rat primary hepatocytes by 3-amino-1,2,4-triazole (ATZ) and mercaptosuccinic acid (MS) results in endogenous oxidative stress and apoptosis. For the present study, we determined whether this apoptosis involved activation of caspase-3, which is known to execute apoptosis in many cell types. ATZ and MS increased levels of reactive oxygen species (ROS) from 3-9 h, just before the onset of chromatin condensation (apoptosis) and decreases in protein thiols. Pretreatment with either SKF, a cytochrome P450 inhibitor, or L-ascorbic acid, an antioxidant, completely suppressed the increase in ROS levels and apoptosis, suggesting that the sustained ROS increases may cause the apoptosis. SKF also abolished the decrease in protein thiol content, further supporting the contribution of the P450 system to increased ROS levels. DEVD-CHO, a caspase-3 inhibitor, even at 1 mM had no effect on apoptosis. Caspase-3 activity remained unchanged and pro-caspase-3 processing was not detected during 18 h incubation with ATZ and MS. Moreover, the amount of unoxidized pro-caspase-3 decreased even below the level of untreated hepatocytes. These findings suggest that the sustained oxidative stress is a major cause for the hepatocyte apoptosis, which occurs independently of the caspase-3 related pathway.

Topics: Amitrole; Animals; Apoptosis; Ascorbic Acid; Caspase 3; Caspases; Hepatocytes; Male; Oxidation-Reduction; Oxidative Stress; Proadifen; Rats; Rats, Wistar; Reactive Oxygen Species; Sulfhydryl Compounds; Thiomalates; Time Factors

Vanadium has been shown to have a number of insulin-like effects and has been demonstrated to be beneficial in the treatment of streptozotocin-diabetic rats when included in the drinking water. However, some signs of toxicity and vanadium accumulation in all analysed tissues were reported in vanadium-treated animals. In the present study, the effect of repeated intraperitoneal administration of sodium 4,5-dihydroxybenzene-1,3-disulfonate (Tiron), ascorbic acid and deferoxamine mesylate (DFOA) or 2-mercaptosuccinic acid on the distribution and excretion of vanadium was determined in male Sprague-Dawley rats. Rats received sodium metavanadate (NaVO3) or vanadyl sulphate pentahydrate (VOSO4.5H2O) in the drinking water at concentrations of 0.15 mg ml-1 (NaVO3) and 0.31 mg ml-1 (VOSO4.5H2O) for 6 weeks. After the end of this exposure period, chelating agents were administered for 2 weeks (3 days per week) at doses approximately equal to one-tenth of their respective LD50. Urine was collected on days 1, 7 and 14 of treatment. Twenty-four hours after the final chelator injection, rats were killed and vanadium concentrations were determined in various tissues. Tiron and DFOA were effective compounds in mobilizing vanadium after NaVO3 administration, whereas Tiron was the most effective chelator after vanadyl sulphate administration. Ascorbic acid neither increased urinary elimination nor decreased tissue vanadium concentrations.

Topics: 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; Administration, Oral; Animals; Ascorbic Acid; Chelating Agents; Deferoxamine; Male; Rats; Rats, Inbred Strains; Thiomalates; Tissue Distribution; Vanadates; Vanadium; Vanadium Compounds