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Oxidative Medicine and Cellular... 2018This investigation is aimed at examining the effects of pharmacological PostC with potassium cyanide (KCN) on functional recovery, gene expression, cytochrome c...
This investigation is aimed at examining the effects of pharmacological PostC with potassium cyanide (KCN) on functional recovery, gene expression, cytochrome c expression, and redox status of isolated rat hearts. Rats were divided into the control and KCN groups. The hearts of male Wistar albino rats were retrogradely perfused according to the technique at a constant perfusion pressure of 70 cmHO. After stabilisation, control hearts were subjected to global ischemia (5 minutes), followed by reperfusion (5 minutes), while experimental hearts underwent global ischemia (5 minutes) followed by 5 minutes of reperfusion with 10 mol/L KCN. The following parameters of heart function were measured: maximum and minimum rates of pressure development, systolic and diastolic left ventricular pressure, heart rate, and coronary flow. Levels of superoxide anion radical, hydrogen peroxide, nitrites, and index of lipid peroxidation (measured as thiobarbituric acid-reactive substances) were measured in coronary venous effluent, and activity of catalase was determined in heart tissue. Expression of Bax, Bcl-2, SOD-1, SOD-2, and cytochrome c was studied as well. It was shown that expression of Bax, Bcl-2, and SOD-2 genes did not significantly differ between groups, while expression of SOD-1 gene and cytochrome c was lower in the KCN group. Our results demonstrated that KCN improved the recovery of myocardial contractility and systolic and diastolic function, enhanced catalase activity, and diminished generation of prooxidants. However, all possible mechanisms and potential adverse effects of KCN should be further examined in the future.
Topics: Animals; Heart; Humans; Ischemia; Male; Myocardial Reperfusion Injury; Oxidative Stress; Potassium Cyanide; Rats; Rats, Wistar
PubMed: 30116485
DOI: 10.1155/2018/5979721 -
Journal of Labelled Compounds &... Nov 2020N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) is a carbodiimide coupling reagent commonly used for the preparation of amides from carboxylic acids and amines....
N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) is a carbodiimide coupling reagent commonly used for the preparation of amides from carboxylic acids and amines. Because of initial concerns regarding the genotoxicity of EDC and its use in GMP syntheses at Bristol Myers Squibb, the quantitation of residual EDC and its by-product N-(3-dimethylaminopropyl)-N'-ethylurea (EDU) by liquid chromatography-mass spectrometry (LCMS) impurity analysis was required. These analyses required the use of stable-isotope-labeled EDC and EDU to serve as internal standards. To meet this need, stable-isotope-labeled EDC 9 and EDU 10 were prepared from [1,2- C ] ethylene glycol and [ C, N] potassium cyanide in overall yields of 6% and 8%, respectively.
Topics: Carbodiimides; Chemistry Techniques, Synthetic; Isotope Labeling; Mass Spectrometry; Methylamines; Urea
PubMed: 32845523
DOI: 10.1002/jlcr.3877 -
Molecules (Basel, Switzerland) May 2022Coumestrol (3,9-dihydroxy-6-benzofuran [3,2-c] chromenone) as a phytoestrogen and polyphenolic compound is a member of the Coumestans family and is quite common in...
Coumestrol (3,9-dihydroxy-6-benzofuran [3,2-c] chromenone) as a phytoestrogen and polyphenolic compound is a member of the Coumestans family and is quite common in plants. In this study, antiglaucoma, antidiabetic, anticholinergic, and antioxidant effects of Coumestrol were evaluated and compared with standards. To determine the antioxidant activity of coumestrol, several methods-namely N,N-dimethyl-p-phenylenediamine dihydrochloride radical (DMPD)-scavenging activity, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical (ABTS)-scavenging activity, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH)-scavenging activity, potassium ferric cyanide reduction ability, and cupric ion (Cu)-reducing activity-were performed. Butylated hydroxyanisole (BHA), Trolox, α-Tocopherol, and butylated hydroxytoluene (BHT) were used as the reference antioxidants for comparison. Coumestrol scavenged the DPPH radical with an IC value of 25.95 μg/mL (r: 0.9005) while BHA, BHT, Trolox, and α-Tocopherol demonstrated IC values of 10.10, 25.95, 7.059, and 11.31 μg/mL, respectively. When these results evaluated, Coumestrol had similar DPPH-scavenging effect to BHT and lower better than Trolox, BHA and α-tocopherol. In addition, the inhibition effects of Coumestrol were tested against the metabolic enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase II (CA II), and α-glycosidase, which are associated with some global diseases such as Alzheimer's disease (AD), glaucoma, and diabetes. Coumestrol exhibited K values of 10.25 ± 1.94, 5.99 ± 1.79, 25.41 ± 1.10, and 30.56 ± 3.36 nM towards these enzymes, respectively.
Topics: Acetylcholinesterase; Antioxidants; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Butyrylcholinesterase; Carbonic Anhydrases; Coumestrol; Free Radical Scavengers; Glycoside Hydrolases; alpha-Tocopherol
PubMed: 35630566
DOI: 10.3390/molecules27103091 -
Journal, Genetic Engineering &... Feb 2023Superoxide dismutase is an important antioxidative stress enzyme which is found in honeybee venom and has a wide pharmaceutical and medical applications.
BACKGROUND
Superoxide dismutase is an important antioxidative stress enzyme which is found in honeybee venom and has a wide pharmaceutical and medical applications.
RESULTS
We reported the purification and characterization of venom SOD from Egyptian honeybee Apis mellifera lamarckii and termed BVSOD. It was purified to homogeneity from the Egyptian honeybee venom. The purification procedures included crude extraction, DEAE-cellulose anion exchange column chromatography, and Sephacryl S-300 gel filtration column chromatography. The purified BVSOD is found to be homogeneous as investigated by native PAGE. It exhibited homodimeric structure with a molecular weight of native form of 32 kDa and subunits of 16.0 kDa. It displayed the maximum activity at pH 7.4. CuCl, ZnCl, and MgCl and elevated the activity of BVSOD, while CoCl, FeCl, and NiCl inhibited BVSOD activity. Potassium cyanide and hydrogen peroxide were most potent inhibitors for BVSOD activity suggesting that it is a Cu/Zn-SOD type.
CONCLUSIONS
The purified BVSOD is found to have antimicrobial and antitumor activities which can be used for various medical and clinical applications.
PubMed: 36807019
DOI: 10.1186/s43141-023-00470-4 -
Clinical Toxicology (Philadelphia, Pa.) Jan 2015More effective, rapidly delivered, safer antidotes are needed for cyanide poisoning. Previous study has demonstrated a beneficial effect of isosorbide dinitrate on the...
CONTEXT
More effective, rapidly delivered, safer antidotes are needed for cyanide poisoning. Previous study has demonstrated a beneficial effect of isosorbide dinitrate on the survival of cyanide-poisoned mice.
OBJECTIVE
To evaluate the effectiveness of isosorbide dinitrate compared with that of sodium nitrite in cyanide poisoning.
MATERIALS AND METHODS
A comparative animal study was performed using 18 rabbits, randomized into 3 study groups. Animals were poisoned intravenously with potassium cyanide (1 mg/kg). The first group was not given any further treatment. The second and third groups were treated intravenously 1 min after poisoning with sodium nitrite (6 mg/kg) and isosorbide dinitrate (50 μg/kg), respectively. The primary outcome was short-term survival of up to 30 min. Secondary outcomes included time to death, a clinical score, mean blood pressure, pulse, blood pH, and lactate and methemoglobin levels.
RESULTS
Rabbits treated with isosorbide dinitrate or sodium nitrite survived while only one untreated rabbit survived. Median time to death of the 5 poisoned and untreated animals was 10 min. All the animals collapsed soon after poisoning, exhibiting rapidly disturbed vital signs and developed lactic metabolic acidosis; average peak blood lactate levels were 15.5-19.1 mmol/L at 10 min after poisoning. The treated animals improved gradually with practically full recovery of the clinical scores, vital signs, and blood gas levels. Sodium nitrite administration raised methemoglobin to an average peak of 7.9%, while isosorbide dinitrate did not change methemoglobin levels.
CONCLUSION
Early administration of isosorbide dinitrate improved the short-term survival of cyanide-poisoned rabbits. Isosorbide dinitrate shows potential as an antidote for cyanide poisoning and may exert its effect using a nitric-oxide-dependent mechanism.
Topics: Acidosis; Administration, Intravenous; Animals; Isosorbide Dinitrate; Male; Methemoglobin; Poisoning; Potassium Cyanide; Rabbits; Sodium Nitrite
PubMed: 25519879
DOI: 10.3109/15563650.2014.990564 -
ACS Infectious Diseases Oct 2016Daptomycin is a lipopeptide antibiotic approved for use against Gram-positive organisms, including highly resistant species. A number of studies have suggested that...
Daptomycin is a lipopeptide antibiotic approved for use against Gram-positive organisms, including highly resistant species. A number of studies have suggested that daptomycin kills bacteria by membrane permeabilization and depolarization. Recently a model membrane system consisting of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol) in a 1:1 ratio and the ionophore CCCP was proposed as a simple model to investigate the mode of action of daptomycin and resistance mechanisms at a molecular level. This study investigates how this model depends on the composition of the membrane and the role of CCCP. Results obtained from a fluorescence assay using pyranine show that daptomycin causes leakage in liposomes of limited stability and that CCCP promotes this leakage. A different model membrane system used here, which relies on ion selective dyes such as 4,4'-[1,4,10,13-tetraoxa-7,16-diazacyclooctadecane-7,16-diylbis(5-methoxy-6,2-benzofurandiyl)]bis-, tetrakis[(acetyloxy)methyl] ester (PBFI), and 4,4'-[1,4,10-trioxa-7,13-diazacyclopentadecane-7,13-diylbis(5-methoxy-6,2-benzofurandiyl)]bis-, tetraammonium salt (SBFI), is a more robust alternative. Findings based on this newer model suggest that daptomycin is selective for potassium.
Topics: Anti-Bacterial Agents; Bacteria; Biological Transport; Cell Membrane; Cell Membrane Permeability; Daptomycin; Potassium; Sodium
PubMed: 27669740
DOI: 10.1021/acsinfecdis.6b00152 -
Journal of Population Therapeutics and... Oct 2019Cyanide is notoriously known to the public for more than a century now as a weapon of mass destruction (Zyklon B gas - hydrogen cyanide used by Nazis), an agent for...
Cyanide is notoriously known to the public for more than a century now as a weapon of mass destruction (Zyklon B gas - hydrogen cyanide used by Nazis), an agent for chemical warfare during World War I (hydrogen cyanide) and very infamous "Suicide Pill" used in the past by military and espionage organizations during World War II (potassium cyanide). During the modern industrial era, cyanide poisoning is commonly associated with the industrial exposure and domestic fires. But there is little awareness about potentially fatal consequences of cyanide poisoning from common food sources. Here, we present the case report of a 79-year-old female with acute cyanide poisoning from improperly prepared cassava leaves. Symptoms from ingested toxin may start a few hours after exposure, which include headache, confusion, ataxia, seizures, palpitations, nausea, vomiting, abdominal pain, flushing, and itching of the skin. Patients may develop hypotension, cardiac arrhythmias, renal failure, hepatic necrosis, rhabdomyolysis, and metabolic acidosis; a multisystem manifestation of hypoxia at the cellular level. Multiple treatment strategies are available to treat cyanide poisoning, including sodium nitrite, sodium thiosulfate, and hydroxycobalamine. This is one of the scenarios where a thorough history, awareness of agents causing cyanide toxicity and knowledge of clinical manifestations can help avoid delays in prompt decision-making for appropriate treatment, thus reducing morbidity, mortality, and prolonged hospital course.
Topics: Aged; Antidotes; Cooking; Cyanides; Female; Humans; Manihot; Plant Leaves; Plants, Edible
PubMed: 31904202
DOI: 10.15586/jptcp.v26i3.633 -
Chemical Research in Toxicology Sep 2022Masitinib is a small molecule tyrosine kinase inhibitor under investigation for the treatment of amyotrophic lateral sclerosis, mastocytosis, and COVID-19....
Masitinib is a small molecule tyrosine kinase inhibitor under investigation for the treatment of amyotrophic lateral sclerosis, mastocytosis, and COVID-19. Hepatotoxicity has been reported in some patients while taking masitinib. The liver injury is thought to involve hepatic metabolism of masitinib by cytochrome P450 (P450) enzymes to form chemically reactive, potentially toxic metabolites. The goal of the current investigation was to determine the P450 enzymes involved in the metabolic activation of masitinib in vitro. In initial studies, masitinib (30 μM) was incubated with pooled human liver microsomes in the presence of NADPH and potassium cyanide to trap reactive iminium ion metabolites as cyano adducts. Masitinib metabolites and cyano adducts were analyzed using reversed-phase liquid chromatography-tandem mass spectrometry. The primary active metabolite, -desmethyl masitinib (M485), and several oxygenated metabolites were detected along with four reactive metabolite cyano adducts (MCN510, MCN524, MCN526, and MCN538). To determine which P450 enzymes were involved in metabolite formation, reaction phenotyping experiments were conducted by incubation of masitinib (2 μM) with a panel of recombinant human P450 enzymes and by incubation of masitinib with human liver microsomes in the presence of P450-selective chemical inhibitors. In addition, enzyme kinetic assays were conducted to determine the relative kinetic parameters (apparent and ) of masitinib metabolism and cyano adduct formation. Integrated analysis of the results from these experiments indicates that masitinib metabolic activation is catalyzed primarily by P450 3A4 and 2C8, with minor contributions from P450 3A5 and 2D6. These findings provide further insight into the pathways involved in the generation of reactive, potentially toxic metabolites of masitinib. Future studies are needed to evaluate the impact of masitinib metabolism on the toxicity of the drug in vivo.
Topics: Activation, Metabolic; Benzamides; COVID-19; Catalysis; Cytochrome P-450 Enzyme System; Humans; Microsomes, Liver; NADP; Piperidines; Potassium Cyanide; Protein Kinase Inhibitors; Pyridines; Thiazoles
PubMed: 36048877
DOI: 10.1021/acs.chemrestox.2c00057 -
Saudi Pharmaceutical Journal : SPJ :... Oct 2023Onion contains many dietary and bioactive components including phenolics and flavonoids. Spiraeoside (quercetin-4-O-β-D-glucoside) is one of the most putative...
Onion contains many dietary and bioactive components including phenolics and flavonoids. Spiraeoside (quercetin-4-O-β-D-glucoside) is one of the most putative flavonoids in onion. Several antioxidant techniques were used in this investigation to assess the antioxidant capabilities of spiraeoside, including 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·) scavenging, N,N-dimethyl-p-phenylenediamine radical (DMPD) scavenging, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical (ABTS) scavenging activities, cupric ions (Cu) reducing and potassium ferric cyanide reduction abilities. In contrast, the water-soluble α-tocopherol analogue trolox and the conventional antioxidants butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), and α-tocopherol were utilized as the standards for evaluation. Spiraeoside scavenged the DPPH radicals an IC of 28.51 μg/mL (r: 0.9705) meanwhile BHA, BHT, trolox, and α-tocopherol displayed IC of 10.10 μg/mL (r: 0.9015), 25.95 μg/mL (r: 0.9221), 7.059 μg/mL (r: 0.9614) and 11.31 μg/mL (r: 0.9642), accordingly. The results exhibited that spiraeoside had effects similar to BHT, but less potent than α-tocopherol, trolox and BHA. Also, inhibitory effects of spiraeoside were evaluated toward some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase II (CA II) and α-glycosidase, which are related to a number of illnesses, such as Alzheimer's disease (AD), diabetes mellitus and glaucoma disorder. Spiraeoside exhibited IC values of 4.44 nM (r: 0.9610), 7.88 nM (r: 0.9784), 19.42 nM (r: 0.9673) and 29.17 mM (r: 0.9209), respectively against these enzymes. Enzyme inhibition abilities were compared to clinical used inhibitors including acetazolamide (for CA II), tacrine (for AChE and BChE) and acarbose (for α-glycosidase). Spiraeoside demonstrated effective antioxidant, anticholinergic, antidiabetic and antiglaucoma activities. With these properties, it has shown that Spiraeoside has the potential to be a medicine for some metabolic diseases.
PubMed: 37693735
DOI: 10.1016/j.jsps.2023.101760 -
PloS One 2018Cyanide fishing, where a solution of sodium or potassium cyanide is used to stun reef fish for easy capture for the marine aquarium and live fish food trades, continues...
Cyanide fishing, where a solution of sodium or potassium cyanide is used to stun reef fish for easy capture for the marine aquarium and live fish food trades, continues to be pervasive despite being illegal in many countries and destructive to coral reef ecosystems. Currently, there is no easy, reliable and universally accepted method to detect if a fish has been exposed to cyanide during the capture process. A promising non-invasive technique for detecting thiocyanate ions, the metabolic byproduct excreted by exposed fish, has been reported in the literature. In an effort to validate this method, four cyanide exposure studies on Amphiprion ocellaris (common clownfish) were carried out over three years. Fish were either exposed to the same (25 ppm) or twice the concentration (50 ppm) as the previsouly published method. Over 100 water samples of fish exposed to cyanide were analyzed by reverse phase HPLC with a C30 column treated with polyethylene glycol and UV detector operating at 220 nm. No thiocyanate was detected beyond the analytical standards and positive controls prepared in seawater. As an alternate means of detecting thiocyanate, water samples and thiocyanate standards from these exposures were derivatized with monobromobimane (MBB) for LC-MS/MS analysis. Thiocyanate was detected in standards with concentrations as low as 0.6 μg/L and quantified to 1 μg/L, but thiocyanate could not be detected in any of the water samples from fish exposed to cyanide with this method either, confirming the HPLC results. Further, we calculated both the mass balance of thiocyanate and the resultant plausible dosage of cyanide from the data reported in the previously published method. These calculations, along with the known lethal dosage of cyanide, further suggests that the detection of thiocyanate in aquarium water is not a viable method for assessing fish exposure to cyanide.
Topics: Animals; Chromatography, High Pressure Liquid; Coral Reefs; Cyanides; Perciformes; Potassium Cyanide; Seawater; Sodium Cyanide; Thiocyanates
PubMed: 29847597
DOI: 10.1371/journal.pone.0196841