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1.
Braz. J. Pharm. Sci. (Online) ; 59: e22459, 2023. graf
Article in English | LILACS | ID: biblio-1439495

ABSTRACT

Abstract Cervical cancer is a leading cause of death among women. The endocervical adenocarcinoma (ECA) represents an aggressive and metastatic type of cancer with no effective treatment options currently available. We evaluated the antitumoral and anti-migratory effects of hypericin (HYP) encapsulated on Pluronic F127 (F127/HYP) photodynamic therapy (PDT) against a human cell line derived from invasive cervical adenocarcinoma (HeLa) compared to a human epithelial cell line (HaCaT). The phototoxicity and cytotoxicity of F127/HYP were evaluated by the following assays: colorimetric assay, MTT, cellular morphological changes by microscopy and long-term cytotoxicity by clonogenic assay. In addition, we performed fluorescence microscopy to analyze cell uptake and subcellular distribution of F127/HYP, cell death pathway and reactive oxygen species (ROS) production. The PDT mechanism was determined with sodium azide and D-mannitol and cell migration by wound-healing assay. The treatment with F127/HYP promoted a phototoxic result in the HeLa cells in a dose-dependent and selective form. Internalization of F127/HYP was observed mainly in the mitochondria, causing cell death by necrosis and ROS production especially by the type II PDT mechanism. Furthermore, F127/HYP reduced the long-term proliferation and migration capacity of HeLa cells. Overall, our results indicate a potentially application of F127/HYP micelles as a novel approach for PDT with HYP delivery to more specifically treat ECA.


Subject(s)
Adenocarcinoma/pathology , Poloxamer/analogs & derivatives , Photochemotherapy/classification , HeLa Cells/classification , Uterine Cervical Neoplasms/pathology , Sodium Azide/administration & dosage , Epithelial Cells/classification , Microscopy, Fluorescence/methods , Neoplasms/pathology
2.
Chem Res Toxicol ; 33(2): 594-603, 2020 02 17.
Article in English | MEDLINE | ID: mdl-31922405

ABSTRACT

Three cobalt-containing macrocyclic compounds previously shown to antagonize cyanide toxicity have been comparatively evaluated for the amelioration of sublethal azide toxicity in juvenile (7-8 weeks) Swiss-Webster mice. The lowest effective doses were determined for hydroxocobalamin, a cobalt porphyrin, and a cobalt-Schiff base macrocycle by giving the antidotes 5 min prior to the toxicant, 27 mg (415 µmol) /kg sodium azide. Both male and female mice were evaluated for their response to the toxicant as well as the antidotes, and no significant differences were noted once weight differences were taken into account. Two of the three compounds significantly decreased the recovery time of azide-intoxicated mice at 10 min after the administration of sodium azide, as determined by a behavioral test (pole climbing). Additionally, azide was determined to cause a several degree drop (∼3 °C) in measured tail temperature, and warming the mice led to a more rapid recovery. The mice were also shown to recover more rapidly when given sodium nitrite, 24 mg (350 µmol)/kg, 5 min after the toxicant; this treatment also suppressed the azide-induced tail temperature decrease. Electron paramagnetic resonance (EPR) measurements of mouse blood treated with sodium azide demonstrated the presence of nitrosylhemoglobin at levels of 10-20 µM which persisted for ∼300 min. The presence of the methemoglobin azide adduct was also detected by EPR at a maximum level of ∼300 µM, but these signals disappeared around 200 min after the administration of azide. The treatment of mice with 15N sodium azide proved that the nitrosylhemoglobin was a product of the administered azide by the appearance of a two-line hyperfine (due to the 15N) in the EPR spectrum of mouse blood.


Subject(s)
Antidotes/pharmacology , Coordination Complexes/pharmacology , Disease Models, Animal , Sodium Azide/antagonists & inhibitors , Sodium Azide/toxicity , Animals , Antidotes/administration & dosage , Cobalt/chemistry , Cobalt/pharmacology , Coordination Complexes/administration & dosage , Electron Spin Resonance Spectroscopy , Electron Transport Complex IV/antagonists & inhibitors , Electron Transport Complex IV/metabolism , Female , Hemoglobins/analysis , Macrocyclic Compounds/chemistry , Macrocyclic Compounds/pharmacology , Male , Mice , Sodium Azide/administration & dosage
3.
Chem Res Toxicol ; 33(2): 333-342, 2020 02 17.
Article in English | MEDLINE | ID: mdl-31599574

ABSTRACT

There is presently no antidote available to treat azide poisoning. Here, the Schiff-base compound Co(II)-2,12-dimethyl-3,7,11,17-tetraazabicyclo-[11.3.1]heptadeca-1(17)2,11,13,15-pentaenyl dibromide (Co(II)N4[11.3.1]) is investigated to determine if it has the capability to antagonize azide toxicity through a decorporation mechanism. The stopped-flow kinetics of azide binding to Co(II)N4[11.3.1] in the absence of oxygen exhibited three experimentally observable phases: I (fast); II (intermediate); and III (slow). The intermediate phase II accounted for ∼70% of the overall absorbance changes, representing the major process observed, with second-order rate constants of 29 (±4) M-1 s-1 at 25 °C and 70 (±10) M-1 s-1 at 37 °C. The data demonstrated pH independence of the reaction around neutrality, suggesting the unprotonated azide anion to be the attacking species. The binding of azide to Co(II)N4[11.3.1] appears to have a complicated mechanism leading to less than ideal antidotal capability; nonetheless, this cobalt complex does protect against azide intoxication. Administration of Co(II)N4[11.3.1] at 5 min post sodium azide injection (ip) to mice resulted in a substantial decrease of righting-recovery times, 12 (±4) min, compared to controls, 40 (±8) min. In addition, only two out of seven mice "knocked down" when the antidote was administered compared to the controls given toxicant only (100% knockdown).


Subject(s)
Antidotes/pharmacology , Antidotes/therapeutic use , Cobalt/pharmacology , Coordination Complexes/pharmacology , Schiff Bases/pharmacology , Sodium Azide/antagonists & inhibitors , Sodium Azide/poisoning , Animals , Antidotes/administration & dosage , Antidotes/chemistry , Cobalt/administration & dosage , Cobalt/chemistry , Cobalt/therapeutic use , Coordination Complexes/administration & dosage , Coordination Complexes/chemistry , Coordination Complexes/therapeutic use , Electron Spin Resonance Spectroscopy , Hydrogen-Ion Concentration , Injections, Intraperitoneal , Male , Mice , Schiff Bases/administration & dosage , Schiff Bases/chemistry , Schiff Bases/therapeutic use , Sodium Azide/administration & dosage , Survival Rate
4.
J Gen Appl Microbiol ; 63(6): 347-354, 2018 Jan 15.
Article in English | MEDLINE | ID: mdl-29142163

ABSTRACT

Microbacterium foliorum GA2, an alkali-tolerant bacterium, was randomly mutated using UV radiation and sodium azide to obtain a mutant with a higher cold-active extracellular amylolytic activity. A mutant, designated as MFSD20, was selected owing to its higher amylase activity at 20°C. Under optimized conditions, amylase production was achieved best with raw banana peels (5000 units) in solid-state fermentation (SSF). The enzyme was purified by salt precipitation and chromatographic methods and afterwards characterized biochemically. The purified enzyme showed maximal activity at temperatures between 15-25°C and at pH 8.0. Interestingly, this mutant biocatalyst (MFSD20) displays higher catalytic activity under conditions of low temperature (4°C) and high pH (10.0), in the presence of SDS (0.1 and 1%), and exhibited 85% and 50% requirement of divalent metallic ions Ca2+ and Mg2+, respectively. This mutant enzyme extract in combination with "Wheel detergent" was highly effective in the removal of tomato sauce and chocolate stains from white cotton fabric was demonstrated by ~50% additional reflectance compared with detergent alone, in a wash performance analysis at 20 ± 2°C. The features shown by mutant M. foliorum GA2 make it a promising candidate for industrial applications involving starch degradation at low temperatures.


Subject(s)
Actinobacteria/enzymology , Cold Temperature , Fermentation , alpha-Amylases/biosynthesis , alpha-Amylases/metabolism , Actinobacteria/genetics , Bacterial Proteins/biosynthesis , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Hydrogen-Ion Concentration , Kinetics , Mutagens/administration & dosage , Mutation/drug effects , Mutation/radiation effects , Sodium Azide/administration & dosage , Starch/metabolism , Ultraviolet Rays , alpha-Amylases/genetics
5.
Stem Cells ; 34(4): 960-71, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26676373

ABSTRACT

Fanconi anemia (FA) is an inherited bone marrow (BM) failure syndrome, presumably resulting from defects in hematopoietic stem cells (HSCs). Normal HSCs depend more on glycolysis than on oxidative phosphorylation (OXPHOS) for energy production. Here, we show that FA HSCs are more sensitive to the respiration inhibitor NaN3 treatment than to glycolytic inhibitor 2-deoxy-d-glucose (2-DG), indicating more dependence on OXPHOS. FA HSCs undergo glycolysis-to-OXPHOS switch in response to oxidative stress through a p53-dependent mechanism. Metabolic stresses induce upregulation of p53 metabolic targets in FA HSCs. Inactivation of p53 in FA HSCs prevents glycolysis-to-OXPHOS switch. Furthermore, p53-deficient FA HSCs are more sensitive to 2-DG-mediated metabolic stress. Finally, oxidative stress-induced glycolysis-to-OXPHOS switch is mediated by synthesis of cytochrome c oxidase 2 (SCO2). These findings demonstrate p53-mediated OXPHOS function as a compensatory alteration in FA HSCs to ensure a functional but mildly impaired energy metabolism and suggest a cautious approach to manipulating p53 signaling in FA.


Subject(s)
Carrier Proteins/biosynthesis , Fanconi Anemia/metabolism , Hematopoietic Stem Cells/metabolism , Mitochondrial Proteins/biosynthesis , Tumor Suppressor Protein p53/genetics , Apoptosis/drug effects , Carrier Proteins/genetics , Deoxyglucose/administration & dosage , Energy Metabolism , Fanconi Anemia/genetics , Fanconi Anemia/pathology , Glycolysis/drug effects , Hematopoietic Stem Cells/pathology , Humans , Mitochondrial Proteins/genetics , Molecular Chaperones , Oxidative Phosphorylation/drug effects , Oxidative Stress/drug effects , Signal Transduction/drug effects , Sodium Azide/administration & dosage , Tumor Suppressor Protein p53/metabolism
6.
Zhongguo Zhong Yao Za Zhi ; 39(3): 488-92, 2014 Feb.
Article in Chinese | MEDLINE | ID: mdl-24946553

ABSTRACT

OBJECTIVE: To observe the effect of synchronous perfusion of specific respiratory chain complex IV inhibitor sodium azide (NaN3) in brain on rat ventromedial prefrontal cortex (mPFC) and acetylcholine (ACh) and choline (Ch) contents in hippocampal extra-cellular fluid, and establish the AD rat model induced by mitochondrial acute injury. METHOD: The synchronous dual-probe dual-channel brain microdialysis sampling technology was applied to synchronously perfuse modified Ringer's solution containing NaN3 (50 micro mol L-1) and neostigmine (2 micro mol L-1) into mPFC and hippocampus of conscious, freely moving normal rats, and continuously collect dialysates from different encephalic areas. Dynamic contents of ACh and Ch were determined by high performance liquid chromatography-post-column immobilized enzyme reactor-electrochemical process. RESULT: ACh and Ch contents in mPFC extracellular fluid of normal rats were higher than that in hippocampus. During the process of perfusion, NaN3 could significantly reduce ACh in mPFC/hippocampal extra-cellular fluid, but remarkably increase Ch, and constantly inhibit the recovery of ACh and Ch contents in mPFC/hippocampus. CONCLUSION: The synchronous perfusion of NaN3in rat mPFC and hippocampus can injure functions of the cholinergic nerve projection area, and cause the acute AD model with ACh and Ch metabolic disorders. This model can be used in pathogenetic and pharmacological studies.


Subject(s)
Extracellular Fluid/drug effects , Extracellular Fluid/metabolism , Hippocampus/cytology , Neurotransmitter Agents/metabolism , Perfusion , Prefrontal Cortex/cytology , Sodium Azide/pharmacology , Acetylcholine/metabolism , Animals , Choline/metabolism , Male , Rats , Rats, Sprague-Dawley , Sodium Azide/administration & dosage , Time Factors
7.
Neurochem Res ; 38(8): 1648-60, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23670089

ABSTRACT

To elucidate the molecular events involved in early ischemic neuronal death, we performed two-dimensional proteome profiling of primary cultures of rat cortical neurons following chemical ischemia induced by the administration of sodium azide under glucose-free conditions. Using a lactic dehydrogenase assay and Western blot analysis of dephosporylation of the voltage-gated potassium channel Kv2.1, we determined duration of chemical ischemia of 2 h to be the relevant time-point for early ischemic neuronal death. Sixty-one proteins were differentially expressed, and 26 different proteins were identified by MALDI-TOF with Mascot database searching. The proteome data indicated that chemical ischemia altered the expression of 20 proteins that are involved in stress response/chaperone, brain development, cytoskeletal/structural proteins, metabolic enzymes, and calcium ion homeostasis. Western blotting and immunocytochemical studies of the 6-most functionally significant proteins showed that, in the ischemia-treated group, the expression of glucose-related protein 78, heat shock protein 90 alpha, and α-enolase was significantly increased, while the expression of inositol triphosphate receptor 1 and ATP synthase beta subunit was decreased. In addition, the expression of dihydropyrimidinase-like 3 showed a truncated pattern in the ischemia group. The changes in the expression of these proteins might be significant indicators of early ischemic neuronal death.


Subject(s)
Cerebral Cortex/metabolism , Ischemia/chemically induced , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Proteomics , Sodium Azide/administration & dosage , Animals , Blotting, Western , Cells, Cultured , Cerebral Cortex/cytology , Electrophoresis, Gel, Two-Dimensional , Phosphorylation , Rats , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
8.
J Nanobiotechnology ; 9: 9, 2011 Mar 25.
Article in English | MEDLINE | ID: mdl-21439072

ABSTRACT

The DNA degradation potential and anti-cancer activities of copper nanoparticles of 4-5 nm size are reported. A dose dependent degradation of isolated DNA molecules by copper nanoparticles through generation of singlet oxygen was observed. Singlet oxygen scavengers such as sodium azide and Tris [hydroxyl methyl] amino methane were able to prevent the DNA degradation action of copper nanoparticles confirming the involvement of activated oxygen species in the degradation process. Additionally, it was observed that the copper nanoparticles are able to exert cytotoxic effect towards U937 and Hela cells of human histiocytic lymphoma and human cervical cancer origins, respectively by inducing apoptosis. The growth characteristics of U937 and Hela cells were studied applying various concentrations of the copper nanoparticles.


Subject(s)
Antineoplastic Agents/pharmacology , Copper/therapeutic use , DNA Damage/drug effects , Metal Nanoparticles/administration & dosage , Singlet Oxygen/pharmacology , Apoptosis/drug effects , Free Radical Scavengers/administration & dosage , HeLa Cells , Humans , Sodium Azide/administration & dosage , Tromethamine/administration & dosage , U937 Cells
9.
Regul Toxicol Pharmacol ; 52(2): 158-62, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18755233

ABSTRACT

Sodium azide (NaN(3)) is being proposed for use as an active ingredient to control a broad spectrum of soil borne pathogens including insects, weeds, nematodes, fungi, and bacteria. The purpose of this study was to determine the maternal and developmental toxicity of NaN(3) in rats. Sperm-positive Sprague-Dawley rats were treated with NaN(3) via oral gavage once daily from Gestation Day (GD) 6 through 19 at respective dose levels of 0, 1, 5, and 17.5mg/kg/day. From GD 10-12, the high-dose was reduced to 10mg/kg/day due to maternal mortality. Cesarean section was performed on GD 20 and implantation and resorptions sites, live and dead fetuses were counted. Fetuses were weighed, sexed externally and processed for gross external, visceral and skeletal examinations. A high rate of maternal mortality; reduced gestation body weight, gestation body weight changes and food consumption; decreased corrected body weight and corrected weight gain were observed at 17.5/10mg/kg/day. Fetal weight was also reduced at 17.5/10mg/kg/day. There were no maternal deaths, clinical signs or body weight effects that were considered related to NaN(3) at 1 and 5mg/kg/day. No increase in the incidence of malformations and variations were observed at any of the doses evaluated. Based on the results of this study, the No Observed Adverse Effect Level (NOAEL) and the Lowest Observed Adverse Effect Level (LOAEL) for maternal and developmental toxicity of NaN(3) in rats were considered to be 5 and 17.5/10mg/kg/day, respectively.


Subject(s)
Abnormalities, Drug-Induced/etiology , Maternal Exposure/adverse effects , Pesticides/toxicity , Sodium Azide/toxicity , Administration, Oral , Animals , Body Weight/drug effects , Dose-Response Relationship, Drug , Eating/drug effects , Female , Fetal Weight/drug effects , Gestational Age , Male , Maternal Mortality , No-Observed-Adverse-Effect Level , Pregnancy , Rats , Rats, Sprague-Dawley , Sodium Azide/administration & dosage
10.
Psychopharmacology (Berl) ; 200(4): 455-64, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18587667

ABSTRACT

RATIONALE: Considerable evidence indicates that brain ethanol metabolism mediated by catalase is involved in modulating some of the behavioral and physiological effects of this drug, which suggests that the first metabolite of ethanol, acetaldehyde, may have central actions. Previous results have shown that acetaldehyde administered into the lateral ventricles produced anxiolysis in a novel open arena in rats. OBJECTIVES: The present studies investigate the effects of centrally formed acetaldehyde on ethanol-induced anxiolysis. MATERIALS AND METHODS: The effects of the catalase inhibitor sodium azide (SA; 0 or 10 mg/kg, IP) on ethanol-induced anxiolysis (0.0, 0.5, or 1.0 g/kg, IP) were evaluated in CD1 mice in two anxiety paradigms, the elevated plus maze and the dark/light box. Additional studies assessed the effect of the noncompetitive catalase inhibitor 3-amino-1,2,4-triazole (AT; 0.5 g/kg, IP) and the acetaldehyde inactivation agent D: -penicillamine (50 mg/kg, IP) on the plus maze. RESULTS: SA reduced the anxiolytic effects of ethanol on several parameters evaluated in the elevated plus maze and in the dark/light box. In the plus maze, AT completely blocked and D-penicillamine significantly reduced the anxiolytic properties of ethanol. CONCLUSIONS: Thus, when cerebral metabolism of ethanol into acetaldehyde is blocked by catalase inhibitors, or acetaldehyde is inactivated, there is a suppressive effect on the anxiolytic actions of ethanol. These data provide further support for the idea that centrally formed or administered acetaldehyde can contribute to some of the psychopharmacological actions of ethanol, including its anxiolytic properties.


Subject(s)
Acetaldehyde/metabolism , Anti-Anxiety Agents/pharmacology , Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Amitrole/pharmacology , Animals , Anti-Anxiety Agents/administration & dosage , Anxiety/drug therapy , Catalase/antagonists & inhibitors , Central Nervous System Depressants/administration & dosage , Darkness , Disease Models, Animal , Dose-Response Relationship, Drug , Ethanol/administration & dosage , Light , Male , Maze Learning/drug effects , Mice , Sodium Azide/administration & dosage , Sodium Azide/pharmacology
11.
Am J Physiol Heart Circ Physiol ; 290(4): H1617-23, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16327018

ABSTRACT

Sodium azide (NaN(3)), a potent vasodilator, causes severe hypotension on accidental exposure. Although NaN(3) has been shown to increase coronary blood flow, the direct effect of NaN(3) on coronary resistance vessels and the mechanism of the NaN(3)-induced response remain to be established. To address these issues without confounding influences from systemic parameters, subepicardial coronary arterioles were isolated from porcine hearts for in vitro study. Arterioles developed basal tone at 60 cmH(2)O intraluminal pressure and dilated acutely, in a concentration-dependent manner, to NaN(3) (0.1 microM to 50 microM). The NaN(3) response was not altered by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester or endothelial removal. Neither inhibition of phosphoinositol 3-kinase and tyrosine kinases nor blockade of ATP-sensitive, Ca(2+)-activated, and voltage-dependent K(+) channels affected NaN(3)-induced dilation. However, the vasomotor action of NaN(3) was significantly attenuated in a similar manner by the inward rectifier K(+) (K(IR)) channel inhibitor Ba(2+), the Na(+)-K(+) ATPase inhibitor ouabain, or the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ). Ba(2+), in combination with either ouabain or ODQ, nearly abolished the vasodilatory response. However, there was no additive inhibition by combining ouabain and ODQ. The NaN(3)-mediated vasodilation was also attenuated by morin, an inhibitor of phosphatidylinositolphosphate (PIP) kinase, which can regulate K(IR) channel activity. With the use of whole cell patch-clamp methods, NaN(3) acutely enhanced Ba(2+)-sensitive K(IR) current in isolated coronary arteriolar smooth muscle cells. Collectively, this study demonstrates that NaN(3), at clinically toxic concentrations, dilates coronary resistance vessels via activation of both K(IR) channels and guanylyl cyclase/Na(+)-K(+)-ATPase in the vascular smooth muscle. The K(IR) channels appear to be modulated by PIP kinase.


Subject(s)
Coronary Vessels/physiology , Myocytes, Smooth Muscle/physiology , Potassium Channels, Inwardly Rectifying/physiology , Sodium Azide/administration & dosage , Sodium-Potassium-Exchanging ATPase/drug effects , Sodium-Potassium-Exchanging ATPase/physiology , Vasodilation/physiology , Animals , Arterioles/drug effects , Arterioles/physiology , Cells, Cultured , Coronary Vessels/drug effects , Enzyme Activation/drug effects , Female , Ion Channel Gating/drug effects , Ion Channel Gating/physiology , Male , Myocytes, Smooth Muscle/drug effects , Potassium Channels, Inwardly Rectifying/agonists , Swine , Vasodilation/drug effects , Vasodilator Agents/administration & dosage
12.
Behav Brain Res ; 154(1): 31-40, 2004 Sep 23.
Article in English | MEDLINE | ID: mdl-15302108

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disorder and accounts for 50-70% of all dementia cases affecting more than 12 million people worldwide. The primary cause of the disease is presently unknown; however, much evidence suggests the involvement of mitochondrial damage. Selective reduction of complex IV activity is present in post-mortem AD brains. Inhibition of this complex could be evoked by chronic sodium azide (NaN(3)) administration in animals. Partial inhibition of the mitochondrial respiratory chain produces free radicals, diminishes aerobic energy metabolism and causes excitotoxic damage creating a deleterious spiral causing neurodegeneration, a pathological process considered to underlie AD. In the present study SPRD rats were treated by various doses of NaN(3) (24-51 mg/kg per day) for 31 days via subcutaneously implanted osmotic minipumps. We have found the proper dose and duration of NaN(3) treatment which was able to cause easily detectable and reproducible cognitive changes. Animals receiving Na-azide doses under 45 mg/kg daily did not show cognitive deficits, but minor histopathological changes were already present. Doses above 45 mg/kg per day proved to be toxic in 4-week-long application causing mortality. NaN(3) dose of 45 mg/kg per day caused cognitive deficit in Morris water maze and passive avoidance tests and a decrease of spontaneous exploratory activity in open field. Histopathological but not biochemical changes were present: dendritic thickening, nerve cell loss, corkscrew-like dendrites and pycnotic nerve cells. The cognitive, behavioural and histopathological features were reproducible. The chronic Na-azide-induced mitochondrial poisoning is suitable for producing AD-like symptoms in rats and testing neuroprotective drug candidates by preventive or curative applications.


Subject(s)
Alzheimer Disease/chemically induced , Behavior, Animal/drug effects , Brain/pathology , Enzyme Inhibitors/toxicity , Sodium Azide/toxicity , Alzheimer Disease/pathology , Alzheimer Disease/physiopathology , Analysis of Variance , Animals , Avoidance Learning/drug effects , Brain/drug effects , Cognition Disorders/chemically induced , Cognition Disorders/pathology , Dose-Response Relationship, Drug , Electron Transport Complex IV/drug effects , Enzyme Inhibitors/administration & dosage , Exploratory Behavior/drug effects , Infusion Pumps , Male , Maze Learning/drug effects , Mitochondria/drug effects , Rats , Rats, Sprague-Dawley , Sodium Azide/administration & dosage , Toxicity Tests, Chronic
13.
Eur J Pharmacol ; 455(2-3): 91-100, 2002 Nov 29.
Article in English | MEDLINE | ID: mdl-12445574

ABSTRACT

We investigated the effects of sigma receptor ligands on neuronal death induced by chemical ischemia using primary cultures of rat cerebral cortical neurons. The induction of chemical ischemia by sodium azide and 2-deoxy-D-glucose led to delayed neuronal death in a time- and concentration-dependent manner, as determined by trypan blue exclusion. The neurotoxicity was inhibited by N-methyl-D-aspartate (NMDA) receptor antagonists, indicating the involvement of glutamate. The sigma receptor ligands (+)-N-allylnormetazocine ((+)-SKF10,047) and haloperidol, but not carbetapentane and R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP), prevented chemical ischemia-induced neurotoxicity in a concentration-dependent manner. The protective effects of (+)-SKF10,047 and haloperidol were not affected by the sigma receptor antagonists. (+)-SKF10,047 and haloperidol, but not carbetapentane and (+)-3PPP, inhibited the glutamate-induced increase in intracellular Ca(2+), and the inhibitory effects were not attenuated by sigma receptor antagonists. These results suggest that direct interaction with NMDA receptors but not sigma receptors is crucial to the neuroprotective effects of sigma receptor ligands with affinity for NMDA receptors.


Subject(s)
Neurons/drug effects , Phenazocine/analogs & derivatives , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, sigma/agonists , 2-Amino-5-phosphonovalerate/pharmacology , Animals , Calcium/metabolism , Calcium/pharmacology , Cell Hypoxia , Cell Survival/drug effects , Cells, Cultured , Cerebral Cortex , Cyclopentanes/pharmacology , Deoxyglucose/administration & dosage , Dizocilpine Maleate/pharmacology , Dose-Response Relationship, Drug , Excitatory Amino Acid Antagonists/pharmacology , Fetus , Glucose/pharmacology , Glutamates/metabolism , Glutamates/pharmacology , Haloperidol/pharmacology , Neurons/cytology , Neurons/metabolism , Phenazocine/pharmacology , Piperidines/pharmacology , Rats , Rats, Wistar , Sodium Azide/administration & dosage
14.
Neurochem Res ; 26(2): 135-43, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11478740

ABSTRACT

Using sodium (NaN3)-induced anoxia plus aglycaemia as a model of chemically-induced ischemia, we have characterized the endogenous release of excitatory and inhibitory amino acids from superfused hippocampal slices. Chemical ischemia produced an azide (1-30 mM) dose-dependent increase in the efflux of glutamate, aspartate and GABA. These increases were attenuated to varying degrees by removal of Ca2+, or the addition of the voltage dependent Na+-channel blocker tetrodotoxin (TTX), the selective Ca2+ channel blockers conotoxin MVIIA, MVIIC, and nifedipine, the NMDA antagonist MK801, the AMPA antagonist GYKI-52466. Similarly, addition of the GLT-1 glutamate transport inhibitor dihydrokainate (DHK) and the anti-estrogen/anion channel blocker tamoxifen also attenuated the efflux of glutamate and GABA. It would therefore appear that the increases in amino acid efflux induced by chemical ischemia originates from both the neuronal pool, via conventional exocytotic release, and glial sources via reversal of the GLT-1 transporter and anion channel regulated cell swelling.


Subject(s)
Amino Acids/metabolism , Glucose/antagonists & inhibitors , Hippocampus/blood supply , Hippocampus/metabolism , Ischemia/chemically induced , Ischemia/metabolism , Sodium Azide , Animals , Dose-Response Relationship, Drug , In Vitro Techniques , Male , Rats , Rats, Sprague-Dawley , Sodium Azide/administration & dosage
15.
Naunyn Schmiedebergs Arch Pharmacol ; 358(3): 367-73, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9774225

ABSTRACT

Sodium azide (NaN3, AZ) is a potent inhibitor and uncoupler of oxidative phosphorylation as well as a nitrovasodilator after being converted to nitric oxide (NO). We studied the effect of intratubular application of AZ on loop of Henle reabsorption and tubuloglomerular feedback (TGF) employing renal micropuncture experiments in nephrons with superficial glomeruli of anesthetized Munich-Wistar-Fromter rats. During perfusion of Henle's loop downstream from an obstructing wax block, AZ (3x10(-5) mol/l and 3x10(-4) mol/l) concentration-dependently increased early distal tubular flow rate and sodium and potassium ion concentration (V(ED), [Na+]ED, [K+]ED). In comparison, application of furosemide (10(-4) mol/l), the action of which is restricted to the water-impermeable thick ascending limb of Henle's loop (TALH) and the macula densa, similarly increased [Na+]ED and [K+]ED, but did not affect V(ED). The effect of AZ on loop of Henle reabsorption appeared to be predominantly localized upstream to the TALH since (1) AZ significantly inhibited net fluid reabsorption (the latter being completely abolished at 3x10(-4) mol/l), (2) the effect of AZ on [Na+]ED and [K+]ED could be mimicked by perfusing the Henle's loop at a flow rate that caused a comparable increase in V(ED) (reflecting a comparable load to TALH), and (3) the effects of AZ and furosemide were additive. In spite of the increase in [Na+]ED and [K+]ED, intratubular application of AZ caused a concentration-dependent inhibition of TGF response, the latter being assessed as the fall in early proximal tubular stop flow pressure during perfusion of Henle's loop at increasing flow rate. Like AZ and furosemide, the NO donor sodium nitroprusside (10(-4) mol/l) blunted the TGF response, but in contrast to furosemide or AZ, it caused a minor decrease in V(ED), without changing [Na+]ED or [K+]ED. The inhibitory effect of AZ on TGF was abolished by the NO scavenger carboxy PTIO. In summary, AZ inhibits both reabsorption in the water-permeable segment of Henle's loop and the TGF response. The effect on reabsorption may be linked to metabolic inhibition rather than NO release, whereas the blunted TGF response appears to involve conversion to NO.


Subject(s)
Diuretics/pharmacology , Enzyme Inhibitors/pharmacology , Furosemide/pharmacology , Loop of Henle/drug effects , Sodium Azide/pharmacology , Absorption/drug effects , Anesthesia , Animals , Enzyme Inhibitors/administration & dosage , Feedback/drug effects , Loop of Henle/metabolism , Male , Nitric Oxide/metabolism , Potassium/metabolism , Punctures , Rats , Sodium/metabolism , Sodium Azide/administration & dosage , Thiopental/analogs & derivatives
16.
Rev. Assoc. Paul. Cir. Dent ; 38(4): 266-72, jul.-ago. 1984. tab
Article in Portuguese | LILACS, BBO - Dentistry | ID: lil-211109

ABSTRACT

Um meio seletivo para Streptococcus mutans foi pesquisado com amostras de coleçäo e com saliva. Verificou-se que o meio, para o isolamento dessa bactéria da saliva, deve conter substâncias inibidoras para bactérias gram-negativas. A azida Sódica mostrou-se mais inibitória para o S. mutans do que o Acetato de Tálio, que, na concentraçäo de 0,1 por cento apresentou melhor resultado para o isolamento dessa espécie na saliva


Subject(s)
Saliva/microbiology , Streptococcus mutans/isolation & purification , Sodium Azide/analysis , Sodium Azide/pharmacokinetics , Sodium Azide , Sodium Azide/administration & dosage , Gram-Negative Bacteria/isolation & purification , Culture Media
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