ascorbic-acid and 1-3-dimethylthiourea

In the present study, we examined the protective effect of N,N'-dimethylthiourea (DMTU), a scavenger of hydroxyl radical (·OH), against water-immersion restraint stress (WIRS)-induced gastric mucosal lesions in rats. When male Wistar rats fasted for 24 h were exposed to WIRS for 3 h, gastric mucosal lesions occurred with increases in the levels of gastric mucosal myeloperoxidase (MPO), an index of tissue neutrophil infiltration, pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin 1beta), lipid peroxide (LPO), and nitrite/nitrate (NOx), an index of nitric oxide synthesis, and decreases in the levels of gastric mucosal nonprotein SH and vitamin C and gastric adherent mucus. DMTU (1, 2.5, or 5 mmol/kg) administered orally at 0.5 h before the onset of WIRS reduced the severity of gastric mucosal lesions with attenuation of the changes in the levels of gastric mucosal MPO, pro-inflammatory cytokines, LPO, NOx, nonprotein SH, and vitamin C and gastric adherent mucus found at 3 h after the onset of WIRS in a dose-dependent manner. Serum levels of corticosterone and glucose, which are indices of stress responses, increased in rats exposed to WIRS for 3 h, but DMTU pre-administered at any dose had no effect on these increases. These results indicate that DMTU protects against WIRS-induced gastric mucosal lesions in rats by exerting its antioxidant action including ·OH scavenging and its anti-inflammatory action without affecting the stress response.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Corticosterone; Cytokines; Gastric Mucosa; Lipid Peroxides; Male; Neutrophil Infiltration; Nitric Oxide; Peroxidase; Protective Agents; Rats; Rats, Wistar; Stomach Ulcer; Stress, Physiological; Thiourea

In hulless barley, H 2 S mediated increases in H 2 O 2 induced by putrescine, and their interaction enhanced tolerance to UV-B by maintaining redox homeostasis and promoting the accumulation of UV-absorbing compounds. This study investigated the possible relationship between putrescence (Put), hydrogen sulfide (H2S) and hydrogen peroxide (H2O2) as well as the underlying mechanism of their interaction in reducing UV-B induced damage. UV-B radiation increased electrolyte leakage (EL) and the levels of malondialdehyde (MDA) and UV-absorbing compounds but reduced antioxidant enzyme activities and glutathione (GSH) and ascorbic acid (AsA) contents. Exogenous application of Put, H2S or H2O2 reduced some of the above-mentioned negative effects, but were enhanced by the addition of Put, H2S and H2O2 inhibitors. Moreover, the protective effect of Put against UV-B radiation-induced damage to hulless barley was diminished by DL-propargylglycine (PAG, a H2S biosynthesis inhibitor), hydroxylamine (HT, a H2S scavenger), diphenylene iodonium (DPI, a PM-NADPH oxidase inhibitor) and dimethylthiourea (DMTU, a ROS scavenger), and the effect of Put on H2O2 accumulation was abolished by HT. Taken together, as the downstream component of the Put signaling pathway, H2S mediated H2O2 accumulation, and H2O2 induced the accumulation of UV-absorbing compounds and maintained redox homeostasis under UV-B stress, thereby increasing the tolerance of hulless barley seedlings to UV-B stress.

Topics: Alkynes; Antioxidants; Ascorbic Acid; Enzyme Inhibitors; Glutathione; Glycine; Homeostasis; Hordeum; Hydrogen Peroxide; Hydrogen Sulfide; Hydroxylamine; NADPH Oxidases; Onium Compounds; Oxidation-Reduction; Oxidative Stress; Plant Proteins; Protective Agents; Putrescine; Seedlings; Signal Transduction; Thiourea; Ultraviolet Rays

Sepsis/multiple organ dysfunction syndrome (MODS) is a major cause of high mortality in the intensive care unit. We have recently reported that 100% oxygen treatment is beneficial to mice with zymosan-induced sterile inflammation by increasing antioxidant enzymatic activities. Yet, the use of hyperoxia is hindered by concerns that it could exacerbate organ injury by increasing free radical formation. It is believed that systemic inflammation and overproduction of reactive oxygen species (ROS) contribute to the mechanism underlying sepsis/MODS. A ROS scavenger has been proven to protect against sepsis/MODS in some animal models. Therefore, we hypothesized that ROS scavenger pretreatment might enhance the protective action of 100% oxygen treatment against zymosan-induced sterile inflammation in mice. In the present study, we showed that 100% oxygen treatment prevented the abnormal changes in serum biochemical parameters, tissue oxygenation, and organ histopathology, and improved the 14-day survival rate in zymosan-stimulated mice, indicating that 100% oxygen treatment had a protective action on sterile inflammation. We found that pretreatment with a ROS scavenger (N-acetylcysteine, vitamin C, or dimethylthiourea) abolished this protective action of 100% oxygen treatment. We also showed that 100% oxygen treatment decreased the levels of serum proinflammatory cytokines (TNF-alpha, IL-6, and high-mobility group box 1), increased the level of serum anti-inflammatory cytokine (IL-10), and upregulated the activities of serum and tissue antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in zymosan-stimulated mice, which were reversed by the pretreatment with a ROS scavenger (N-acetylcysteine, vitamin C, or dimethylthiourea). We thus conclude that ROS scavenger pretreatment partly abolishes the protective effects of 100% oxygen treatment on sterile inflammation in mice by regulating inflammatory cytokines as well as antioxidant enzymes.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Cytokines; Free Radical Scavengers; Heart; Inflammation; Kidney; Liver; Lung; Male; Mice; Multiple Organ Failure; Myocardium; Oxygen; Reactive Oxygen Species; Sepsis; Thiourea; Zymosan

Exposure to visible-light causes the photoinactivation of certain bacteria by a process that is believed to involve the photo-stimulation of endogenous intracellular porphyrins. Studies with some bacterial species have reported that this process is oxygen-dependent. This study examines the role of oxygen in the visible-light inactivation of Staphylococcus aureus. Suspensions of S. aureus were exposed to broadband visible-light under both oxygen depletion and oxygen enhancement conditions to determine whether these environmental modifications had any effect on the staphylococcal inactivation rate. Oxygen enhancement was achieved by flowing oxygen over the surface of the bacterial sample during light inactivation and results demonstrated an increased rate of staphylococcal inactivation, with approximately 3.5 times less specific dose being required for inactivation compared to that for a non-enhanced control. Oxygen depletion, achieved through the addition of oxygen scavengers to the S. aureus suspension, further demonstrated the essential role of oxygen in the light inactivation process, with significantly reduced staphylococcal inactivation being observed in the presence of oxygen scavengers. The results of the present study demonstrate that the presence of oxygen is important for the visible-light inactivation of S. aureus, thus providing supporting evidence that the nature of the mechanism occurring within the visible-light-exposed staphylococci is photodynamic inactivation through the photo-excitation of intracellular porphyrins.

Topics: Ascorbic Acid; Catalase; Light; Oxygen; Reactive Oxygen Species; Staphylococcus aureus; Thiourea

The role of H2O2 in abscisic acid (ABA)-induced rice leaf senescence is investigated. ABA treatment resulted in H2O2 production in rice leaves, which preceded the occurrence of leaf senescence. Dimethylthiourea, a chemical trap for H2O2, was observed to be effective in inhibiting ABA-induced senescence, ABA-increased matondialdehyde (MDA) content, ABA-increased antioxidative enzyme activities (superoxide dismutase, ascorbate peroxidase, glutathione reductase and catalase), and ABA-decreased antioxidant contents (ascorbic acid and reduced glutathione) in rice leaves. Diphenyteneiodonium chloride (DPI) and imidazole (IMD), inhibitors of NADPH oxidase, and KCN and NaN3, inhibitors of peroxidase, prevented ABA-induced H2O2 production, suggesting NADPH oxidase and peroxidase are H2O2-generating enzymes in ABA-treated rice leaves. DPI, IMD, KCN, and NaN3 also inhibited ABA-promoted senescence, ABA-increased MDA contents, ABA-increased antioxidative enzyme activities, and ABA-decreased antioxidants in rice leaves. These results suggest that H2O2 is involved in ABA-induced senescence of rice leaves.

Topics: Abscisic Acid; Ascorbate Peroxidases; Ascorbic Acid; Catalase; Glutathione; Glutathione Reductase; Hydrogen Peroxide; Lipid Peroxidation; Malondialdehyde; Oryza; Peroxidases; Plant Growth Regulators; Plant Leaves; Plant Proteins; Superoxide Dismutase; Thiourea; Time Factors

We report on a deposition of oxalate crystals on ferruginous bodies after occupational exposure to asbestos demonstrated in 3 patients. We investigated the mechanism and possible significance of this deposition by testing the hypothesis that oxalate generated through nonenzymatic oxidation of ascorbate by asbestos-associated iron accounts for the deposition of the crystal on a ferruginous body. Crocidolite asbestos (1000 microg/mL) was incubated with 500 micromol H(2)O(2) and 500 micromol ascorbate for 24 hours at 22 degrees C. The dependence of oxalate generation on iron-catalyzed oxidant production was tested with the both the metal chelator deferoxamine and the radical scavenger dimethylthiourea. Incubation of crocidolite, H(2)O(2), and ascorbate in vitro generated approximately 42 nmol of oxalate in 24 hours. Oxalate generation was diminished significantly by the inclusion of either deferoxamine or dimethylthiourea in the reaction mixture. Incubation of asbestos bodies and uncoated fibers isolated from human lung with 500 micromol H(2)O(2) and 500 micromol ascorbate for 24 hours at 22 degrees C resulted in the generation of numerous oxalate crystals. We conclude that iron-catalyzed production of oxalate from ascorbate can account for the deposition of this crystal on ferruginous bodies.

Topics: Asbestos, Crocidolite; Asbestosis; Ascorbic Acid; Calcium Oxalate; Crystallization; Crystallography, X-Ray; Deferoxamine; Fatal Outcome; Humans; Hydrogen Peroxide; Iron; Iron Chelating Agents; Lung; Male; Middle Aged; Oxidation-Reduction; Thiourea

It has been recently shown that glycated human haemoglobin induces endothelial dysfunction in rat vessels by generating superoxide anions that interfere with nitric oxide mediated responses. Our study analysed the effect of glycated human haemoglobin on the endothelium-dependent relaxations of human vessels.. Omental microvessels were obtained from patients (without diabetes, hypertension or vascular disease) during surgery and mounted in a small vessel myograph to study their vasoactive responses (vessels from 3-7 patients for each set of experiments).. Cumulative vasodilatory responses to bradykinin (10 nmol/l to 3 mumol/l) were induced in vessels precontracted with 35-50 mmol/l potassium chloride. Addition of 100 mumol/l NG-nitro-L-arginine methyl ester reduced the relaxation evoked by bradykinin, but preincubation with both NG-nitro-L-arginine methyl ester and 10 mumol/l indomethacin was needed to abolish it. Bradykinin-induced responses were inhibited by 1 mumol/l non-glycated oxyhaemoglobin whereas no effect was obtained with 10 nmol/l oxyhaemoglobin. At these low concentrations (10 nmol/l), glycated human oxyhaemoglobin caused an impairment of bradykinin-induced relaxation when the percentage of glycation was 10% or higher. This effect was prevented by preincubating the vessels with ascorbic acid (10 mumol/l), superoxide dismutase (100 U/ml) and gliclazide (1 and 10 mumol/l), but not with indomethacin (10 mumol/l), catalase (400-600 U/ml), dimethylthiourea (1 mmol/l) or glibenclamide (10 mumol/l). In vessels preincubated with NG-nitro-L-arginine methyl ester (100 mumol/l), glycohaemoglobin did not add any additional effect.. Highly glycated human oxyhaemoglobin, at physiological plasmatic concentrations, impairs nitric oxide-mediated responses by a mechanism involving superoxide anions but not cyclooxygenase derivatives.

Topics: Animals; Ascorbic Acid; Bradykinin; Catalase; Free Radical Scavengers; Gliclazide; Glycated Hemoglobin; Humans; In Vitro Techniques; Indomethacin; Microcirculation; NG-Nitroarginine Methyl Ester; Nitric Oxide; Omentum; Potassium Chloride; Rats; Splanchnic Circulation; Superoxide Dismutase; Thiourea; Vasodilation

Prostaglandin F(2alpha) (PGF(2alpha)) is implicated in the process of luteal regression in many species. Treatment of rat luteal tissue with PGF(2alpha) increases the generation of reactive oxygen species. Since reactive oxygen species have been implicated in apoptosis, the present study was undertaken to determine whether reactive oxygen species play a role in the PGF(2alpha)-induced apoptosis of rat luteal cells. Rat luteal cells were loaded with 6-carboxy-2, 7'-dichlorodihydro-fluorescein (CDCFH) diacetate, di (acetomethyl ester), which can be oxidized by reactive oxygen species to yield CDCF, a fluorescent molecule, and the cells were treated with different doses of PGF(2alpha). Incubation with 100 micromol PGF(2alpha) l(-1) induced an increase in CDCF fluorescence (P < 0. 05). Treatment of cells with PGF(2alpha) for 48 h in serum-free medium induced a dose-dependent increase in cell death, and these cells exhibited the morphological characteristics typical of apoptosis, including condensed or fragmented nuclei and fragmentation of internucleosomal DNA. Pretreatment of these cells with ascorbic acid, N,N'-dimethylthiourea, or superoxide dismutase, which acts as an antioxidant or a radical scavenger, prevented the PGF(2alpha)-induced apoptosis. These results demonstrate that PGF(2alpha) produces reactive oxygen species and induces apoptosis in rat luteal cells, indicating that the reactive oxygen species may induce apoptotic cell death during luteolysis.

Topics: Analysis of Variance; Animals; Antioxidants; Apoptosis; Ascorbic Acid; Cells, Cultured; Corpus Luteum; Dinoprostone; DNA Fragmentation; Female; Free Radical Scavengers; Least-Squares Analysis; Luteolysis; Microscopy, Fluorescence; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Superoxide Dismutase; Thiourea

Iron compounds formed in the degradation of a hematoma can accelerate the formation of free radicals in adjacent ischemic or hypoperfused tissue. The purpose of this study was to examine the efficacy of compounds that quench free radicals in improving the outcome in rats with experimental intracerebral hemorrhage. Intracerebral hemorrhage was induced in rats by injection of bacterial collagenase and heparin into the caudate nucleus. Rats were treated with alpha-tocopherol plus ascorbic acid starting before hemorrhage, or with dimethylthiourea or alpha-phenyl-N-tert-butyl nitrone starting 2 h after hemorrhage, with treatment continued for 10 days after induction of hemorrhage. Outcome was assessed by behavioral analyses, magnetic resonance imaging, and histopathology. A trend towards behavioral improvement was found for rats treated with alpha-tocopherol/ascorbic acid, while behavior was significantly improved following intracerebral hemorrhage in rats treated with dimethylthiourea or alpha-phenyl-N-tert-butyl nitrone. These results suggest that free radicals may play a role in the development of brain injury following intracerebral hemorrhage, and that compounds that interrupt the free radical cascade may improve outcome. However, treatment did not significantly affect edema, resolution of the hematoma, or neuronal injury in tissue adjacent to the hemorrhage.

Topics: Animals; Ascorbic Acid; Behavior, Animal; Body Temperature; Cerebral Hemorrhage; Cyclic N-Oxides; Feeding Behavior; Free Radical Scavengers; Free Radicals; Magnetic Resonance Imaging; Male; Neurologic Examination; Neuroprotective Agents; Nitrogen Oxides; Rats; Rats, Sprague-Dawley; Thiourea; Vitamin E

The recent literature suggests that free radicals and reactive oxygen species may account for many pathologies, including those of the nervous system.. The influence of various reactive oxygen species on the rate of glutamate uptake by astrocytes was investigated on monolayers of primary cultures of mouse cortical astrocytes.. Hydrogen peroxide and peroxynitrite inhibited glutamate uptake in a concentration-dependent manner. Addition of copper ions and ascorbate increased the potency and the efficacy of the hydrogen peroxide effect, supporting the potential neurotoxicity of the hydroxyl radical. The free radical scavenger dimethylthiourea effectively eliminated the inhibitory potential of a mixture containing hydrogen peroxide, copper sulphate, and ascorbate on the rate of glutamate transport into astrocytes. The inhibitory effect of hydrogen peroxide on glutamate uptake was not altered by the inhibition of glutathione peroxidase, whereas the inhibition of catalase by sodium azide clearly potentiated this effect. Superoxide and nitric oxide had no effect by themselves on the rate of glutamate uptake by astrocytes. The absence of an effect of nitric oxide is not due to an inability of astrocytes to respond to this substance, since the same cultures did respond to nitric oxide with a sustained increase in cytoplasmic free calcium.. These results confirm that reactive oxygen species have a potential neurotoxicity by means of impairing glutamate transport into astrocytes, and they suggest that preventing the accumulation of hydrogen peroxide in the extracellular space of the brain, especially during conditions that favor hydroxyl radical formation, could be therapeutic.

Topics: Animals; Animals, Newborn; Antioxidants; Ascorbic Acid; Astrocytes; Catalase; Free Radical Scavengers; Glutamic Acid; Glutathione Peroxidase; Hydrogen Peroxide; Mice; Mice, Inbred C57BL; Nitrates; Nitric Oxide; Reactive Oxygen Species; Superoxides; Thiourea

Whether a reduction in urinary protein excretion in rats coadministered puromycin aminonucleoside and antioxidants was associated with a reduction in alterations to glomerular epithelial cell (podocyte) ultrastructure was examined. Daily urinary protein excretion was measured in rats that received a single i.v. injection of saline or puromycin aminonucleoside with or without coadministration of antioxidants. The coadministration of alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase to puromycin aminonucleoside-treated rats reduced proteinuria by approximately 90, 40, and 60%, respectively, over the 18-day period studied. For a second group of rats, daily urinary protein excretion was measured and kidneys were processed for light microscopy and transmission and scanning electron microscopy 4, 5, and 10 days after injection. Transmission electron microscopic morphometric analysis of glomeruli from puromycin aminonucleoside-treated rats coadministered antioxidants revealed significantly reduced foot process effacement on Days, 4, 5, and 10 compared with rats that received puromycin aminonucleoside alone. Thus, at Day 10, puromycin aminonucleoside-treated rats coadministered alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase contained 90, 74, and 88% (P < 0.01 in all cases) more glomerular epithelial cell filtration slits per unit length of glomerular basement membrane than rats treated with puromycin aminonucleoside alone. In contrast, by scanning electron microscopy, the antioxidants were found to provide no protection against the changes occurring in glomerular epithelial cell bodies and major processes. These results provide further evidence of a role for reactive oxygen species in puromycin aminonucleoside nephrosis and indicate that the antioxidants provide protection against the changes occurring in glomerular epithelial cell foot processes.

Topics: Animals; Antioxidants; Ascorbic Acid; Body Weight; Diuresis; Female; Kidney Glomerulus; Microscopy, Electron; Proteinuria; Puromycin Aminonucleoside; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Thiourea; Vitamin E

The isolated perfused working rat heart model of cardiopulmonary bypass and ischaemic cardiac arrest has been used to investigate whether addition of various organic anti-oxidants to the St Thomas' Hospital cardioplegic solution can enhance the recovery of function of the rat myocardium after normothermic (37 degrees C) global ischaemic arrest. Five anti-oxidants were studied: (i) ascorbate (1.0 and 10.0 mmol.litre-1), (ii) methionine (1.0 and 10.0 mmol.litre-1), (iii) reduced glutathione (1.0 and 10.0 mmol.litre-1), (iv) dimethylthiourea (0.1, 1.0, 10.0 and 50.0 mmol.litre-1), (v) N-2-mercaptopropionyl glycine (0.1, 1.0 and 10.0 mmol.litre-1). The recovery of aortic flow in control hearts which were free of anti-oxidant was 50.7(SEM 0.5)%; ascorbate (1.0 or 10.0 mmol.litre-1) improved this recovery to 72.1(1.7) and 70.2(0.3)% respectively; methionine (1.0 and 10.0 mmol.litre-1) improved the recovery to 74.1(5.7)% and 67.7(1.7)%, respectively; reduced glutathione (1.0 and 10.0 mmol.litre-1) improved the recovery to 66.7(1.4)% and 74.0(1.7)% respectively. In further studies, the addition of dimethylthiourea (0.1, 1.0 and 10.0 mmol.litre-1) to the cardioplegic solution failed to improve recovery of aortic flow [47.3(8.0), 24.6(7.3), 48.0(7.7)% respectively] when compared to its anti-oxidant free control value of 40.4(6.1)% and at a concentration of 50.0 mmol.litre-1 a very poor recovery of aortic flow of 7.7(4.8)% was observed. Mercaptopropionyl glycine (0.1, 1.0 and 10.0 mmol.litre-1) also failed to improve the recovery of aortic flow [34.7(1.6), 34.7(7.7) and 25.6(5.4)% respectively.2+ Since biological membranes are highly permeable to dimethylthiourea and mercaptopropionyl glycine, it is possible that they accumulate in the intracellular compartment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antioxidants; Ascorbic Acid; Bicarbonates; Calcium Chloride; Cardioplegic Solutions; Cardiopulmonary Bypass; Free Radicals; Heart Arrest, Induced; In Vitro Techniques; Magnesium; Male; Methionine; Myocardial Reperfusion Injury; Potassium Chloride; Rats; Rats, Inbred Strains; Sodium Chloride; Thiourea; Tiopronin

Oxygen free radicals have recently been found to mediate cell injury after ischemia in the kidney. We sought to determine whether oxygen free radicals mediate damage in mercuric chloride (HgCl2)-induced acute renal failure, a toxic model of acute renal failure. Neither superoxide dismutase nor allopurinol, which scavenges or inhibits production of superoxide radical, respectively, provided protection against renal dysfunction after HgCl2. Similarly, the hydroxyl radical scavengers tryptophan, N-acetyl-tryptophan, and ascorbic acid were unable to protect against HgCl2. However, dimethylthiourea and dimethyl sulfoxide, both hydroxyl radical scavengers, were beneficial. Dimethylthiourea completely prevented the rise in plasma creatinine concentration after HgCL2. In control rats plasma creatinine concentration rose from 0.4 mg/dl to 3.2 +/- 0.8, 5.1 +/- 1.0, and 6.1 +/- 1.6 mg/dl at 24, 48, and 72 hours after HgCl2. Dimethylthiourea-treated rats had plasma creatinine concentration less than 0.5 mg/dl at all times. Furthermore, a mixture of HgCl2 and equimolar amounts of dimethylthiourea was less toxic than HgCl2 alone. Dimethyl sulfoxide attenuated the HgCl2-induced rise in creatinine concentration: 1.3 +/- 0.2, 3.2 +/- 0.3, and 3.1 +/- 0.2 mg/dl at 24, 48, and 72 hours after HgCl2. Measurement of kidney malondialdehyde content after HgCl2 provided no evidence for oxygen free radical-mediated lipid peroxidation. We conclude that there is no convincing role for oxygen free radicals in the pathogenesis of HgCl2-induced acute renal failure. The ability of dimethylthiourea and dimethyl sulfoxide to protect against HgCl2-induced renal dysfunction may be related to their ability to form complexes with Hg2+.

Topics: Acute Kidney Injury; Allopurinol; Animals; Ascorbic Acid; Creatinine; Dimethyl Sulfoxide; Drug Interactions; Kidney Cortex; Lipid Peroxides; Male; Mercuric Chloride; Rats; Superoxide Dismutase; Thiourea; Tryptophan