ascorbic-acid and zinc-chloride

The disruption of copper homeostasis and the oxidative stress induced by Cu-amyloids are crucial features of Alzheimer's disease pathology. The copper specific N

Topics: Aminoquinolines; Amyloid beta-Peptides; Ascorbic Acid; Carrier Proteins; Chelating Agents; Chlorides; Copper; Homeostasis; Humans; Molecular Structure; Oxidation-Reduction; Oxidative Stress; Peptide Fragments; Reactive Oxygen Species; Zinc Compounds

Initiation of celiac disease is triggered in the gastrointestinal tract by transglutaminase 2 (TG2) assisted deamidation of gluten peptides. Deamidation is a side-reaction to transamidation and occurs if primary amines are absent. In contrast to deamidation, transamidation does not trigger an immune response. The aim of the study was to identify a suitable food additive that interacts with TG2 binding motives in gluten-derived peptides to prevent deamidation/transamidation. Homology modelling of α2-gliadin and computational screening of compounds for their binding affinity to a common TG2 binding motive (P)QLP were done by using computational approaches followed by experimental testing of TG2 activity. A database containing 1174 potential food grade ligands was screened against the model of α2-gliadin (27 out of 33 aa). Out of the five best ligands, ascorbyl palmitate, was observed to decrease TG2 transamidation of gliadin by 82% ± 2%. To completely silence the transamidation, we added zinc chloride (ZnCl

Topics: Ascorbic Acid; Celiac Disease; Chlorides; Drug Evaluation, Preclinical; Epitopes, T-Lymphocyte; Food Additives; Genetic Predisposition to Disease; Gliadin; GTP-Binding Proteins; Humans; Lymphocyte Activation; Models, Molecular; Molecular Docking Simulation; Pilot Projects; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases; Zinc Compounds

A one-pot synthesis method for the fabrication of biomass-derived activated carbon-zinc oxide (ZAC) nanocomposites using sugarcane bagasse as a carbon precursor and ZnCl2 as an activating agent is reported. For the first time, we used ZnCl2 as not only an activating agent and also for the synthesis of ZnO nanoparticles on the AC surface. ZAC materials with varying ZnO loading were prepared and characterized by a variety of analytical and spectroscopic techniques such as FE-SEM, FE-TEM, XRD, EA, XPS, and Raman spectroscopy. ZAC-modified glassy carbon electrodes (GCEs) were found to exhibit remarkable electrochemical properties for simultaneous detection of ascorbic acid (AA), dopamine (DA), and uric acid (UA) as well as hazardous pollutants such as hydrogen peroxide (H2O2) and hydrazine (N2H4) with desirable sensitivity, selectivity, and detection limits. Moreover, ZAC-modified stainless steel electrodes also showed superior performances for supercapacitor applications. The ZAC nanocomposites, which may be mass produced by the reported facile direct route from sugarcane bagasse, are not only eco-friendly but also cost-effective, and thus, are suitable as a practical platform for bio-sensing and energy storage applications.

Topics: Ascorbic Acid; Biosensing Techniques; Carbon; Cellulose; Chlorides; Dopamine; Electric Capacitance; Electric Power Supplies; Electrodes; Green Chemistry Technology; Hydrazines; Hydrogen Peroxide; Limit of Detection; Nanocomposites; Particle Size; Porosity; Saccharum; Uric Acid; Zinc Compounds; Zinc Oxide

This work investigated zinc (Zn) and mercury (Hg) effects on oxidative parameters, markers of toxicity and metal levels in different tissues from non-lactating rats (NLR) and lactating rats (LR). Adult NLR and LR received ZnCl2 (27mg/kg) or saline (0.9%) subcutaneously and after 24h they received HgCl2 (5mg/kg) or saline (0.9%). Twenty four hours later, they were sacrificed and the preparation of biological material and biochemical analyses were performed. With respect to oxidative parameters, Hg exposure decreased kidney total SH levels from NLR and LR and hepatic catalase activity (not statistically significant) in NLR. Zinc pre-treatment partly prevented the decrease of kidney total SH levels in LR. Zinc per se increased hepatic non-protein SH levels of NLR and LR. Regarding toxicity markers, Hg exposure inhibited the δ-aminolevulinic acid dehydratase (δ-ALA-D) activity from kidney and liver of NLR, inhibited serum alanine aminotransferase (ALT) activity of LR and increased serum creatinine and urea levels of NLR and LR. Zinc pre-exposure prevented the enzymatic alterations caused by Hg. NLR and LR Hg exposed presented accumulation of mercury in the kidney, liver, blood and urine. Zinc pre-treatment prevented this accumulation partly in NLR liver and blood and completely in LR kidney and liver. These results show that NLR and LR are differently sensitive to HgCl2 and that ZnCl2 showed a promising effect against Hg toxicity.

Topics: Alanine Transaminase; Animals; Ascorbic Acid; Catalase; Chlorides; Creatinine; Female; Kidney; Lactation; Liver; Mercuric Chloride; Organ Specificity; Porphobilinogen Synthase; Protective Agents; Rats, Wistar; Sulfhydryl Compounds; Urea; Zinc Compounds

The aim of the present study was to evaluate the possible effects of zinc chloride against the gastrointestinal lesions caused by oral administration of ethanol in rats. Rats were divided into five groups, namely, saline, ethanol, zn, zn+ethanol and ethanol+zn. Ethanol 70% (2 mL/kg) was administered by gavage in 36 h fasted rats. Zinc chloride (27 mg/kg, ~13 mg/kg of zinc) was given by gavage 1h before or 1h after the administration of ethanol. Oral administration of ethanol consistently induced damage in the rat glandular stomach and intestine. Zinc did not demonstrate effect per se and significantly reduced gastrointestinal lesions when administered either before or after lesion induction. Ethanol induced enhancement of thiobarbituric acid reactive substance and reactive species levels, diminished the ascorbic acid and total protein SH content as well as superoxide dismutase and catalase activity in stomach and intestine of rats. Zinc treatment prevented and reversed these alterations induced by ethanol. Stomach and intestine of rats treated with zinc presented higher zinc content than the tissues of rats treated only with ethanol. Non-protein SH content was not altered by any treatment. Results suggested that the gastrointestinal protective effect of zinc in this experimental model could be due to its antioxidant effect.

Topics: Animals; Antioxidants; Ascorbic Acid; Catalase; Chlorides; Ethanol; Gastric Mucosa; Lipid Peroxidation; Male; Rats; Rats, Wistar; Reactive Oxygen Species; Sulfhydryl Compounds; Superoxide Dismutase; Zinc Compounds

Organoselenium compounds have important pharmacological properties. However, these compounds can cause toxicity, typically related to oxidation of endogenous thiols. The aim of this study was to investigate whether 2,2'-dithienyl diselenide (DTDS) has potential toxicity in vitro and in vivo. Therefore, sulfhydryl-containing enzyme activities, δ-aminolevulinic acid dehydratase (δ-ALA-D) and Na(+) -K(+) -ATPase were used to predict DTDS toxicity in rat brain homogenate in vitro. In in vivo experiments, a DTDS administration (50 or 100 mg kg(-1) , p.o.) to rats was performed and toxicological parameters were determined. DTDS inhibited δ-ALA-D (IC50 2 µm) and Na(+) -K(+) -ATPase (IC50 17 µm) activities in vitro. The inhibitory effect of DTDS on δ-ALA-D and Na(+) -K(+) -ATPase activities was restored by dithiothreitol. DTDS (5-25 µm) elicited a thiol oxidase-like activity. In vivo, DTDS (50 and 100 mg kg(-1) ) caused systemic toxicity, evidenced by a decrease in water and food intakes and body weight gain, as well as the death of rats. DTDS at the dose of 100 mg kg(-1) increased plasma alanine and aspartate aminotransferase activities and decreased urea levels. At 50 and 100 mg kg(-1) , it increased lipid peroxidation levels. At the highest dose, DTDS inhibited δ-ALA-D activity. By contrast, Na(+) -K(+) -ATPase activity and antioxidant defense were not altered in the brains of rats exposed to DTDS. In conclusion, interaction with the cisteinyl residues seems to mediate the inhibitory effect of DTDS on sulfhydryl-containing enzymes in vitro. In addition, high oral doses of DTDS induce toxicity in rats.

Topics: Animals; Antioxidants; Ascorbic Acid; Brain; Catalase; Chemical and Drug Induced Liver Injury; Chlorides; Drinking; Eating; Enzyme Inhibitors; Female; Glutathione; Kidney Diseases; Lipid Peroxidation; Male; Organoselenium Compounds; Oxidoreductases Acting on Sulfur Group Donors; Porphobilinogen Synthase; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Superoxide Dismutase; Thiophenes; Weight Gain; Zinc Compounds

We recently reported that induction of metallothionein (MT) was critical in limiting nickel (Ni)-induced lung injury in intact mice. Nonetheless, the mechanism by which Ni induces MT expression is unclear. We hypothesized that the ability of Ni to mobilize zinc (Zn) may contribute to such regulation and therefore, we examined the mechanism for Ni-induced MT2A expression in human airway epithelial (BEAS-2B) cells. Ni induced MT2A transcript levels and protein expression by 4 hours. Ni also increased the activity of a metal response element (MRE) promoter luciferase reporter construct, suggesting that Ni induces MRE binding of the metal transcription factor (MTF-1). Exposure to Ni resulted in the nuclear translocation of MTF-1, and Ni failed to induce MT in mouse embryonic fibroblasts lacking MTF-1. As Zn is the only metal known to directly bind MTF-1, we then showed that Ni increased a labile pool of intracellular Zn in cells as revealed by fluorescence-activated cell sorter using the Zn-sensitive fluorophore, FluoZin-3. Ni-induced increases in MT2A mRNA and MRE-luciferase activity were sensitive to the Zn chelator, TPEN, supporting an important role for Zn in mediating the effect of Ni. Although neither the source of labile Zn nor the mechanism by which Ni liberates labile Zn was apparent, it was noteworthy that Ni increased intracellular reactive oxygen species (ROS). Although both N-acetyl cysteine (NAC) and ascorbic acid (AA) decreased Ni-induced increases in ROS, only NAC prevented Ni-induced increases in MT2A mRNA, suggesting a special role for interactions of Ni, thiols, and Zn release.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Bronchi; Cell Separation; Cells, Cultured; Chelating Agents; Chlorides; DNA-Binding Proteins; Epithelial Cells; Ethylamines; Flow Cytometry; Fluorescent Dyes; Humans; Metallothionein; Mice; Mice, Knockout; Nickel; Polycyclic Compounds; Pyridines; Pyrimidines; Reactive Oxygen Species; RNA, Messenger; Time Factors; Transcription Factor MTF-1; Transcription Factors; Transcriptional Activation; Transfection; Up-Regulation; Zinc Compounds

The effect of cadmium (Cd(2+)) on delta-aminolevulinate dehydratase (delta-ALA-D) activity from rat lung in vitro was investigated. delta-ALA-D activity, a parameter for metal intoxication, has been reported as a target of Cd(2+) in different tissues. The protective effect of monotherapies with dithiol chelating (meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS)) or antioxidant agents (ascorbic acid, diphenyl diselenide (PhSe)(2), and N-acetylcysteine (NAC)) was evaluated. The effect of a combined therapy (dithiol chelatingxantioxidant agent) was also studied. Zinc chloride (ZnCl(2)) and dithiothreitol (DTT) were used to investigate the mechanisms involved in cadmium, chelating and antioxidant effects on delta-ALA-D activity. Cadmium inhibited rat lung delta-ALA-D activity at low concentrations. DTT (3mM), but not ZnCl(2) (100microM), protected the inhibition of enzyme activity caused by Cd(2+). Chelating agents were not effective in restoring the enzyme activity. DMPS and DMSA presented inhibitory effect on enzyme activity. DTT restored the inhibition caused by both chelating agents, but ZnCl(2) restored only the inhibitory effect induced by DMSA. These compounds caused a marked potentiation of delta-ALA-D inhibition induced by Cd(2+). ZnCl(2) did not restore inhibition of enzyme activity caused by Cd(2+) plus chelating agents. Conversely, DTT restored the inhibition induced by Cd(2+)/DMSA, but not by Cd(2+)/DMPS. Antioxidants were not effective in ameliorating delta-ALA-D inhibition induced by Cd(2+), whereas ascorbic acid potentiated the enzyme inhibition induced by this metal. A combined effect of Cd(2+)xDMPSx(PhSe)(2) and Cd(2+)xDMPSxNAC was observed. There was no combined effect of Cd(2+)xchelatorxantioxidants when DMSA was used. This study demonstrated that Cd(2+)inhibited delta-ALA-D activity and chelating and antioxidant agents, alone or combined, did not restore the enzyme activity. In contrast, these compounds potentiated the inhibition induced by Cd(2+) in rat lung.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Cadmium Chloride; Chelating Agents; Chlorides; Dithiothreitol; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Environmental Pollutants; Enzyme Inhibitors; Lung; Male; Organoselenium Compounds; Porphobilinogen Synthase; Rats; Rats, Wistar; Succimer; Unithiol; Zinc Compounds

The detection of DNA radicals by immuno-spin trapping (IST) is based on the trapping of radicals with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), forming stable nitrone adducts that are then detected using an anti-DMPO serum. DNA radicals are very reactive species, and because they are paramagnetic they have previously been detected only by electron spin resonance (ESR) with or without spin trapping, which is not available in most bioresearch laboratories. IST combines the simplicity, reliability, specificity and sensitivity of spin trapping with heterogeneous immunoassays for the detection of DNA radicals, and complements existing methods for the measurement of oxidatively generated DNA damage. Here we have used IST to demonstrate that DMPO traps Cu(II)-H(2)O(2)-induced DNA radicals in situ and in real time, forming DMPO-DNA nitrone adducts, but preventing both 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) formation and DNA fragmentation. We also applied IST to detect DNA radicals in rat hepatocytes exposed to Cu(II) and H(2)O(2) under nonlethal conditions.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Ascorbic Acid; Cell Nucleus; Chlorides; Copper; Cyanides; Cyclic N-Oxides; Deoxyguanosine; Deuterium Oxide; DNA; DNA Fragmentation; Enzyme-Linked Immunosorbent Assay; Female; Free Radicals; Glutathione; Hepatocytes; Histidine; Hydrogen Peroxide; Immunoassay; Nitrogen Oxides; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Spin Trapping; Thiourea; Zinc Compounds

This study investigated the involvement of NMDA receptors and the L-arginine-nitric oxide (NO) pathway in the antidepressant-like effects of zinc in the forced swimming test (FST). The immobility times in the FST and in the tail suspension test (TST) were reduced by zinc chloride (ZnCl(2), 30 and 10-30 mg/kg intraperitoneal (i.p.), respectively). The doses active in the FST and TST reduced locomotor activity in an open-field. The antidepressant-like effect of ZnCl(2) in the FST was prevented by pre-treatment of animals with guanosine 5'-monophosphate (GMP), ascorbic acid, L-arginine, or S-nitroso-N-acetyl-penicillamine (SNAP), but not with D-arginine, administered at doses that per se produced no anti-immobility effect. The immobility time of mice treated with ZnCl(2)+MK-801 was not different from the result obtained with ZnCl(2) or MK-801 alone, but ZnCl(2)+imipramine had a greater effect in the FST than administration of either drug alone. Pre-treatment of animals with a sub-threshold dose of ZnCl(2) prevented the anti-immobility effect of MK-801, ketamine, GMP, L-arginine or N(G)-nitro-L-arginine (L-NNA), but did not alter the effect of imipramine or fluoxetine. Taken together, the results demonstrate that zinc produced an antidepressant-like effect that seems to be mediated through its interaction with NMDA receptors and the L-arginine-NO pathway.

Topics: Animals; Antidepressive Agents; Arginine; Ascorbic Acid; Behavior, Animal; Chlorides; Depression; Dizocilpine Maleate; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Excitatory Amino Acid Antagonists; Female; Fluoxetine; Free Radical Scavengers; Guanosine Monophosphate; Hindlimb Suspension; Imipramine; Immobilization; Ketamine; Male; Mice; Motor Activity; Nitric Oxide; Nitric Oxide Donors; Pain Measurement; Receptors, N-Methyl-D-Aspartate; S-Nitroso-N-Acetylpenicillamine; Swimming; Time Factors; Zinc Compounds

Cystinuria, an inherited disease, is clinically diagnosed by detecting cystine in urine. A colorimetric method using sodium cyanide and sodium nitroprusside is a simple qualitative test used to detect cystinuria. Several colorimetric methods have been proposed for quantitative analysis of cystine; however, we found that none of them were satisfactory because the results were not reproducible. The causes of non-reproducible results were: (1) insufficient reduction time for conversion of cystine to cysteine, and (2) the interference of creatinine. In this report, we present a method to quantitate cystine in urine. We also found that ascorbic acid and ferric chloride, but not zinc chloride, interfered with the color reaction. Using this method, 15 normal urine samples (10 males and 5 females) and 12 cystine stone forming patients' (5 males and 7 females) urine were analyzed. The method was compared to commercially available urine controls. Only captopril showed a dose dependent response and color intensity at 521 nm. Thiola and D-penicillamine showed little effect on cystine determination.

Topics: Adult; Artifacts; Ascorbic Acid; Captopril; Chlorides; Colorimetry; Creatinine; Cyanides; Cysteine; Cystinuria; Dose-Response Relationship, Drug; Female; Ferrous Compounds; Humans; Male; Middle Aged; Nitroprusside; Penicillamine; Reference Values; Reproducibility of Results; Serum Albumin; Tiopronin; Zinc Compounds

Differential pulse polarography (DPP) was applied to measure metallothionein (MT) content in the RH-35 rat hepatoma cell. The method was sensitive in measuring MT at nanogram concentrations. The MT measurement was not interfered by small molecular weight proteins. Cellular MT content increased upon incubated in medium containing different concentrations of CdCl2 or ZnCl2. The increase was concentration-dependent. In the case of CdCl2, significant increase in cellular MT content was observed at a level as low as 0.18 mg/l. The change in MT occurred when there was no significant change in cell viability or cellular protein content. The concentration of ZnCl2 needed to induce the same amount of MT as that with 0.18 mg/l CdCl2 was 12 mg/l. At high concentrations (> 12 mg/l), ZnCl2 also caused an increase in cellular protein content. Therefore, when calculation was based on cellular protein content, ZnCl2 did not caused further increase in MT. L-ascorbic caused significant increase in cellular MT content when it was presented at levels above 100 mg/l but not at 50 mg/l. The effect of L-ascorbic acid on MT induction was not dose-dependent. At 150 mg/l, the amount of MT induced was not different from that with 100 mg/l. Thus, L-ascorbic might not directly influence cellular MT content. Cysteine at 4 and 40 mg/l did not increase cellular MT content. The results of this study showed that cellular MT content could be measured by DPP. Our finding that CdCl2 at sub-lethal concentrations can effectively induce MT suggests that MT may serve as an early warning signal prior to serve as an early warning signal prior to the occurrence of cell death.

Topics: Animals; Ascorbic Acid; Cadmium Chloride; Cell Survival; Chlorides; Cysteine; Dose-Response Relationship, Drug; Liver Neoplasms, Experimental; Metallothionein; Polarography; Rats; Reproducibility of Results; Tumor Cells, Cultured; Zinc Compounds