ascorbic-acid and 2-5-dihydroxybenzoic-acid

Topics: Ascorbic Acid; Blood Transfusion; Chelating Agents; Deferoxamine; Diet; Gentisates; Hemochromatosis; Hemosiderosis; Hydroxamic Acids; Hydroxybenzoates; Iron; Piperazines; Syndrome

For the sake of safety it would be desirable to store and transport the ready-for-use liquid formulation (diagnostics and therapeutics) of radiolabelled peptides. The use of ethanol, in combination with a mixture of gentisic- and ascorbic acid, has superior effects on stabilizing radiolabelled somatostatin analogs. As a consequence, (111)In- and (177)Lu-labelled somatostatin analogs can be stored and transported in a single-vial ready-for-use liquid formulation up to 7 days after radiolabelling.

Topics: Ascorbic Acid; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Drug Stability; Drug Storage; Ethanol; Gentisates; Humans; Indium Radioisotopes; Lutetium; Radioisotopes; Radiopharmaceuticals; Solutions; Somatostatin

Ascorbate (AA), an antioxidant substance known as vitamin C, exists in the brain at a high concentration, although transfer into the brain after systemic administration of AA itself is limited. Intraperitoneal administration of dehydroascorbate (DHA) resulted in a rapid and progressive increase in extracellular AA in rat striatum in a dose-dependent manner. DHA administration increased 2,3- and 2,5-dihydroxybenzoate (2,3- and 2,5-DHBA) formation from salicylate in parallel with the increase in extracellular AA. Intrastriatal administration of active AA oxidase (AAO), but not the inactivated enzyme, completely suppressed the increase in 2,3- and 2,5-DHBA formation after the DHA administration. These findings suggest that extracellular AA might stimulate hydroxyl radical (OH) generation in the striatum. This is supported by the observation of dose-dependent OH generation upon intrastriatal administration of AA itself. In addition, deferoxamine, an iron chelator, decreased basal 2,3- and 2,5-DHBA formation and strongly, though not completely, suppressed the DHA-induced increase of 2,3- and 2,5-DHBA formation. Therefore, increased extracellular AA might function as a prooxidant and stimulate OH generation in cooperation with iron in rat striatum.

Topics: Animals; Ascorbic Acid; Behavior, Animal; Corpus Striatum; Dehydroascorbic Acid; Extracellular Space; Gentisates; Hydroxybenzoates; Hydroxyl Radical; Male; Microdialysis; Rats; Rats, Sprague-Dawley

Reactive oxygen species are implicated in the aetiology of a range of human diseases and there is increasing interest in their role in the development of cancer.. To develop a suitable method for the detection of reactive oxygen species produced by the faecal matrix.. A refined high performance liquid chromatography system for the detection of reactive oxygen species is described.. The method allows baseline separation of the products of hydroxyl radical attack on salicylic acid in the hypoxanthine/xanthine oxidase system, namely 2,5-dihydroxybenzoic acid, 2,3-dihydroxybenzoic acid, and catechol. The increased efficiency and precision of the method has allowed a detailed evaluation of the dynamics of reactive oxygen species generation in the faecal matrix. The data show that the faecal matrix is capable of generating reactive oxygen species in abundance. This ability cannot be attributed to the bacteria present, but rather to a soluble component within the matrix. As yet, the nature of this soluble factor is not entirely clear but is likely to be a reducing agent.. The soluble nature of the promoting factor renders it amenable to absorption, and circumstances may exist in which either it comes into contact with either free or chelated iron in the colonocyte, leading to direct attack on cellular DNA, or else it initiates lipid peroxidation processes whereby membrane polyunsaturated fatty acids are attacked by reactive oxygen species propagating chain reactions leading to the generation of promutagenic lesions such as etheno based DNA adducts.

Topics: Ascorbic Acid; Bacteria; Catechols; Chromatography, High Pressure Liquid; Edetic Acid; Feces; Free Radical Scavengers; Gentisates; Humans; Hydroxybenzoates; Hydroxyl Radical; Hypoxanthine; Phytic Acid; Reactive Oxygen Species; Salicylic Acid; Xanthine Oxidase

The healing-promotion property of saliva has been observed in the past, but its underlying mechanism has never been elucidated. We hypothesized a mechanism based on salivary proteins binding to redox active metal ions, rendering them nonactive in their capacity for free radical production.. Examination of this mechanism was conducted by comparing the redox activity of protein-rich saliva with protein-poor saliva. We also examined the redox activity mediated by these 2 kinds of saliva following the in vitro addition of iron, copper, and manganese. Saliva samples were analyzed for their redox activity by measuring the ascorbate-driven and saliva (diluted 1:2)-mediated conversion of salicylate to its 2,3- and 2.5-dihydroxybenzoates and catechol metabolites.. The concentrations of salicylate metabolites formed by protein-rich saliva were significantly lower by 45% (P < .05), 66% (P < .01), and 54% (P < .05), respectively, when compared with those formed by protein-poor saliva. The capacity of saliva in suppressing redox activity was found to be inversely related to the concentrations of iron and copper added (but not manganese), but correlated well with the protein content. When the highest concentrations of iron (15 mumol/L) and copper (10 mumol/L) were added to protein-rich saliva, the concentrations of salicylate metabolites produced were only 0.3% to 1% of those of non-saliva-containing controls (P < .01). However, when these concentrations of iron and copper were added to protein-poor saliva, significantly higher values of redox activity were detected, and the concentrations of the salicylate derivatives produced were 2.1% to 8.1% of those of non-saliva-containing controls (P < .01). In contrast, when the lowest concentrations of iron (2 mumol/L) and copper (0.1 mumol/L) were added, 2.8 to 4 times lower concentrations of salicylate derivatives were produced (P < .01).. These results substantiate our hypothesis that saliva has a profound capacity for reducing redox activity rendered by transition metal ions, correlating well with its protein content.

Topics: Ancitabine; Animals; Antimetabolites, Antineoplastic; Antioxidants; Ascorbic Acid; Catechols; Copper; Free Radicals; Gentisates; Hydroxybenzoates; Iron; Iron Chelating Agents; Male; Manganese; Metals; Oxidation-Reduction; Parasympathomimetics; Parotid Gland; Pilocarpine; Protein Binding; Rats; Rats, Wistar; Salicylates; Saliva; Salivary Proteins and Peptides; Wound Healing

We wished to determine whether histidine scavenges hydroxyl radical, H2O2, and superoxide anion in vitro and to investigate the protective effect of histidine on isolated perfused rat hearts after global ischemia (40 min) and reperfusion (30 min) (I/R). Left ventricular (LV) function was recorded and coronary effluent was collected for measurement of lactate dehydrogenase (LDH) before ischemia and at 5, 10, 15, and 30 min of reperfusion. At the end of the experiment, a portion of the LV wall was fixed with 2% glutaraldehyde for morphological analysis; the remaining heart was immediately frozen in liquid nitrogen for determination of adenine nucleotides. Histidine effectively quenched hydroxyl radicals and H2O2, but not superoxide anions, in in vitro and in vivo conditions. Hearts treated with histidine exhibited significantly greater functional recovery during reperfusion as compared with nontreated hearts (p < 0.05). Cell morphology was well preserved, and enzyme release was significantly attenuated by histidine treatment (p < 0.05). Histidine raised the ATP level to 73% and the creatine phosphate level to 68% of normal control during reperfusion. Total adenine nucleotide pool and energy charge rate in histidine-treated hearts significantly increased as compared with those in nontreated hearts (p < 0.05), but no effect on ATP and creatine phosphate was noted during ischemia, Histidine prevents postischemic reperfusion injury in isolated heart by inhibiting reactive O2 species and preserving high-energy phosphates (HEP).

Topics: Adenosine Triphosphate; Animals; Ascorbic Acid; Chromatography, High Pressure Liquid; Disease Models, Animal; Free Radical Scavengers; Gentisates; Glutaral; Heart Ventricles; Histidine; Hydrogen Peroxide; Hydroxybenzoates; Hydroxyl Radical; L-Lactate Dehydrogenase; Male; Myocardial Reperfusion Injury; Phosphates; Phosphocreatine; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Superoxides; Tissue Embedding; Ventricular Function, Left

The levels of hydroxyl radicals and oxidized GSH have been examined as indices of oxidative stress in young (3 months), middle-aged (15 months), and old (20-24 months) gerbil brain hippocampus, cortex, and striatum. The hydroxyl radical stress was estimated by measuring the salicylate hydroxyl radical trapping products 2,5- and 2,3-dihydroxybenzoic acid. The stress was significantly higher in all three brain regions in middle-aged and old gerbils versus young animals (< or = 66.0%). Regional comparisons showed that the stress was significantly higher in cortex than in either the hippocampus or striatum of the middle-aged and old gerbils (< or = 32.0%). The ratio of oxidized to total GSH also increased progressively in middle-aged and old animals in all three brain regions (p < 0.05, < or = 41.1%), further indicating a general age-related increase in oxidative stress. Parallel to this age-related increase in oxidative stress, a significant, albeit slight (8%), decrease in neuronal number in hippocampal CA1 region was observed in both the middle-aged and old animals. Possible differences in antioxidant levels were also examined. Total GSH levels were similar across age groups (variance < 12%). However, the regional comparison showed that it was highest in striatum in all age groups. The levels of alpha-tocopherol (vitamin E) were significantly higher in the middle-aged and old animals in all three regions (< or = 70.4%). Vitamin E was highest in the hippocampus and the differences between the hippocampus and the cortex and striatum increased with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Animals; Antioxidants; Ascorbic Acid; Body Water; Brain; Cerebral Cortex; Corpus Striatum; Gentisates; Gerbillinae; Glutathione; Hippocampus; Hydroxybenzoates; Hydroxyl Radical; Male; Neurons; Organ Specificity; Oxidation-Reduction; Pyramidal Tracts; Vitamin E

The biodistributions of different Tc-MDP complexes, separated from different MDP preparations by anionic exchange chromatography, were investigated. We included MDP preparations from one producer with both ascorbic and gentisic acid as stabilizing agent and one preparation with ascorbic acid from a second producer. Bone to soft tissue ratios in rats were compared for the different Tc-MDP complexes separated. It seems that the elution profile of the radiochromatogram may indicate the biodistribution of the preparation. Ascorbic acid and gentisic acid caused different elution profiles and the different complexes isolated were demonstrated to have different bone to muscle ratios.

Topics: Animals; Ascorbic Acid; Bone and Bones; Chromatography, Ion Exchange; Excipients; Gentisates; Hydroxybenzoates; Male; Radionuclide Imaging; Rats; Rats, Inbred Strains; Technetium Tc 99m Medronate; Tissue Distribution

The biodistribution of four 99mTc labelled MDP preparations with different stabilizing agents were studied in young rats. The study was performed with MDP gentisic acid as a standard versus MDP ascorbic acid and MDP PABA. All results were tested statistically by the Wilcoxon-van-Eltern test.

Topics: 4-Aminobenzoic Acid; Animals; Ascorbic Acid; Excipients; Gentisates; Hydroxybenzoates; Rats; Technetium Tc 99m Medronate; Tissue Distribution

The oxidation state of technetium-99m, reduced by concentrated hydrochloric acid and evaporation until dryness, was determined by radiochromatography. The dry deposits of reduced 99mTc were allowed to react with DTPA and MDP with and without antioxidants present. The formation of 99mTc(IV)-DTPA and 99mTc(IV)-MDP complexes and the influence of the antioxidants gentisic and ascorbic acids were studied by radiochromatography and by biodistributional studies in rabbits. 99mTc(IV)-MDP complexes thus formed were demonstrated to have the same biodistribution in rabbits as 99mTc-MDP complexes formed by a conventional stannous reduction kit technique.

Topics: Animals; Ascorbic Acid; Gentisates; Hydroxybenzoates; Organometallic Compounds; Oxidation-Reduction; Pentetic Acid; Rabbits; Technetium Tc 99m Medronate; Technetium Tc 99m Pentetate; Tissue Distribution

Mitochondria are known to contain a P-450 like system similar to that found in microsomes. Since previous in vivo studies from this laboratory have suggested that renal mitochondria may metabolize salicylate (SAL) to a reactive intermediate capable of protein binding, the ability of isolated kidney and liver mitochondria to activate salicylate was investigated. Renal mitochondria were 4 times more active than liver in converting SAL to a reactive intermediate and metabolized approx. 1% of the SAL to 2,3-dihydroxybenzoic acid, the catechol analogue of SAL. The formation of 2,3-dihydroxybenzoate (2,3-DHBA) and the amount of radiolabel bound to mitochondrial protein was decreased in the presence of SKF 525-A; however, excess unlabeled metabolite had no effect on binding. These data indicate that kidney mitochondria activate SAL via a cytochrome P-450 like system, but suggest that the binding species is not 2,3-DHBA itself. Oxidation of SAL and covalent binding of radiolabel, however, were also observed after the addition of ferrous iron and ascorbic acid to a model system containing [14C]SAL and bovine serum albumin. Mannitol decreased SAL oxidation and covalent binding, suggesting radical formation may represent a non-enzymatic mechanism for SAL activation.

Topics: Animals; Ascorbic Acid; Chromatography, Thin Layer; Ferrous Compounds; Gentisates; Hydroxybenzoates; In Vitro Techniques; Kidney; Male; Mannitol; Mitochondria, Liver; Proadifen; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid

The in vitro effects of ascorbic acid, acetaminophen, salicylic acid, and gentisic acid on home blood-glucose-measurement systems were studied. Whole blood in the normoglycemic range was spiked with quantities of each study drug at low, moderate, and high therapeutic concentrations. The glucose concentration of the blood was measured using Chemstrip bG, Dextrostix, and Visidex II home blood-glucose-monitoring systems. Serum samples were also measured by two automated systems, a glucose-oxidase method and a hexokinase method. Mean values were compared within the same glucose-measurement system to determine the extent of drug interference, and to values obtained by other systems to determine the reliability among systems. Changes between the control and treatment glucose mean concentrations of 20% or more were considered clinically important. Drug interference was observed with all three home blood-glucose-measurement systems and was drug-concentration dependent. Both automated systems were associated with drug interference at the highest concentration of salicylic acid, and the hexokinase method was influenced at the highest concentration of gentisic acid. No clinically important differences were observed between the automated systems; however, differences were observed between the automated and home blood-glucose-monitoring systems. Salicylic acid, acetaminophen, and ascorbic acid interfere with home blood-glucose-measurement systems. Switching between home blood-glucose-measurement systems could result in a poor assessment of blood-glucose values. In general, the values determined by home and automated systems should not be compared clinically.

Topics: Acetaminophen; Ascorbic Acid; Blood Glucose; Drug Interactions; Gentisates; Glucose Oxidase; Humans; Hydroxybenzoates; Indicators and Reagents; Monitoring, Physiologic; Reagent Kits, Diagnostic; Salicylates; Salicylic Acid