-
Life (Basel, Switzerland) Oct 2022Cyanide (CN) pollution in agricultural systems can affect crop production. However, no data are available to describe the full picture of the responsive metabolic...
Cyanide (CN) pollution in agricultural systems can affect crop production. However, no data are available to describe the full picture of the responsive metabolic mechanisms of genes with known functions related to exogenous KCN exposure. In this study, we examined the transcriptome in rice seedlings exposed to potassium cyanide (KCN) using an Agilent 4×44K rice microarray to clarify the relationship between the differentially expressed genes (DEGs) and their function classifications. The number of DEGs (up-regulated genes/down-regulated genes) was 322/626 and 640/948 in the shoots and roots of CN-treated rice seedlings, respectively. Functional predication demonstrated that a total of 534 and 837 DEGs in shoots and roots were assigned to 22 COG categories. Four common categories listed on the top five COG classifications were detected in both rice tissues: signal transduction mechanisms, carbohydrate transport and metabolism, post-translational modification, protein turnover and chaperones, and transcription. A comparison of DEGs aligned to the same COG classification demonstrated that the majority of up-regulated/down-regulated DEGs in rice tissues were significantly different, suggesting that responsive and regulatory mechanisms are tissue specific in CN-treated rice seedlings. Additionally, fifteen DEGs were aligned to three different COG categories, implying their possible multiple functions in response to KCN stress. The results presented here provide insights into the novel responsive and regulatory mechanisms of KCN-responsive genes, and will serve as useful resources for further functional dissections of the physiological significance of specific genes activated in the exogenous KCN stress response in rice plants.
PubMed: 36362856
DOI: 10.3390/life12111701 -
Toxicological Sciences : An Official... Jan 2023Cyanide-a fast-acting poison-is easy to obtain given its widespread use in manufacturing industries. It is a high-threat chemical agent that poses a risk of occupational...
Cyanide-a fast-acting poison-is easy to obtain given its widespread use in manufacturing industries. It is a high-threat chemical agent that poses a risk of occupational exposure in addition to being a terrorist agent. FDA-approved cyanide antidotes must be given intravenously, which is not practical in a mass casualty setting due to the time and skill required to obtain intravenous access. Glyoxylate is an endogenous metabolite that binds cyanide and reverses cyanide-induced redox imbalances independent of chelation. Efficacy and biochemical mechanistic studies in an FDA-approved preclinical animal model have not been reported. Therefore, in a swine model of cyanide poisoning, we evaluated the efficacy of intramuscular glyoxylate on clinical, metabolic, and biochemical endpoints. Animals were instrumented for continuous hemodynamic monitoring and infused with potassium cyanide. Following cyanide-induced apnea, saline control or glyoxylate was administered intramuscularly. Throughout the study, serial blood samples were collected for pharmacokinetic, metabolite, and biochemical studies, in addition, vital signs, hemodynamic parameters, and laboratory values were measured. Survival in glyoxylate-treated animals was 83% compared with 12% in saline-treated control animals (p < .01). Glyoxylate treatment improved physiological parameters including pulse oximetry, arterial oxygenation, respiration, and pH. In addition, levels of citric acid cycle metabolites returned to baseline levels by the end of the study. Moreover, glyoxylate exerted distinct effects on redox balance as compared with a cyanide-chelating countermeasure. In our preclinical swine model of lethal cyanide poisoning, intramuscular administration of the endogenous metabolite glyoxylate improved survival and clinical outcomes, and ameliorated the biochemical effects of cyanide.
Topics: Swine; Animals; Cyanides; Disease Models, Animal; Antidotes; Hemodynamics; Glyoxylates; Poisoning
PubMed: 36326479
DOI: 10.1093/toxsci/kfac116 -
Molecules (Basel, Switzerland) Oct 2022Allyl halides with triflamide under oxidative conditions form halogen-substituted amidines. Allyl cyanide reacts with triflamide in acetonitrile or THF solutions in the...
Allyl halides with triflamide under oxidative conditions form halogen-substituted amidines. Allyl cyanide reacts with triflamide in acetonitrile or THF solutions in the presence of NBS to give the products of bromotriflamidation with a solvent interception, whereas in CHCl two regioisomers of the bromotriflamidation product without a solvent interception were obtained. The formed products undergo base-induced dehydrobromination to give linear isomers with the new C=C bond conjugated either with the nitrile group or the amidine moiety or alkoxy group. Under the same conditions, the reaction of allyl alcohol with triflamide gives rise to amidine, which was prepared earlier by the reaction of diallyl formal with triflamide. Unlike their iodo-substituted analogs, bromo-substituted amidines successfully transform into imidazolidines under the action of potassium carbonate.
Topics: Amidines; Solvents; Nitriles; Acetonitriles; Halogens; Imidazolidines
PubMed: 36296503
DOI: 10.3390/molecules27206910 -
Biology Sep 2022Recombinant DNA technology offered the creation of new combinations of DNA segments that are not found together in nature. The present study aimed to produce an...
Recombinant DNA technology offered the creation of new combinations of DNA segments that are not found together in nature. The present study aimed to produce an ecofriendly bioremediation model to remediate cyanide pollution from a polluted marine system. Cyanide is a known toxic compound produced through natural and anthropogenic activities. An -mediated genetic transformation technique was used to generate transformed using plant expression vector pTRA-K-cTp carries isolated coding sequence of the cyanobacterial cyanase gene () isolated from (PCC6803). qRT-PCR analysis showed the overexpression of in transgenic , as compared with the respective wild type. Growth parameters and biochemical analyses were performed under cyanide stress conditions using transgenic and wild for evaluating the effect of the presence of the cyanobacterial cyanase gene in algae. The transgenic strain () showed promising results for cyanide bioremediation in polluted water samples. Cyanide depletion assays and algal growth showed a significant resistance in the transgenic type against cyanide stress, as compared to the wild type. Genetically modified alga showed the ability to phytoremediate a high level of potassium cyanide (up to150 mg/L), as compared to the wild type. The presence of the gene has induced a protection response in , which was shown in the results of growth parameter analyses. Therefore, the present study affirms that transgenic the coding gene is a potential effective ecofriendly bioremediator model for the remediation of cyanide pollutants in fresh water.
PubMed: 36290324
DOI: 10.3390/biology11101420 -
ACS Pharmacology & Translational Science Oct 2022Binuclear molybdenum sulfur complexes are effective for the catalytic conversion of cyanide into thiocyanate. The complexes themselves exhibit low toxicity and high...
Characterization of a Threonine-Ligated Molybdenyl-Sulfide Cluster as a Putative Cyanide Poisoning Antidote; Intracellular Distribution, Effects on Organic Osmolyte Homeostasis, and Induction of Cell Death.
Binuclear molybdenum sulfur complexes are effective for the catalytic conversion of cyanide into thiocyanate. The complexes themselves exhibit low toxicity and high aqueous solubility, which render them suitable as antidotes for cyanide poisoning. The binuclear molybdenum sulfur complex [(thr)MoO(μ-S)(S)] (thr - threonine) was subjected to biological studies to evaluate its cellular accumulation and mechanism of action. The cellular uptake and intracellular distribution in human alveolar (A549) cells, quantified by inductively coupled plasma mass spectrometry (ICP-MS) and cell fractionation methods, revealed the presence of the compound in cytosol, nucleus, and mitochondria. The complex exhibited limited binding to DNA, and using the expression of specific protein markers for cell fate indicated no effect on the expression of stress-sensitive channel components involved in cell volume regulation, weak inhibition of cell proliferation, no increase in apoptosis, and even a reduction in autophagy. The complex is anionic, and the sodium complex had higher solubility compared to the potassium. As the molybdenum complex possibly enters the mitochondria, it is considered as a promising remedy to limit mitochondrial cyanide poisoning following, , smoke inhalation injuries.
PubMed: 36268119
DOI: 10.1021/acsptsci.2c00093 -
ChemPlusChem Apr 2023A co-crystalline adduct consisting of a phosphinine selenide and an organohalide was obtained by slow evaporation of the solvent from a mixture of...
A co-crystalline adduct consisting of a phosphinine selenide and an organohalide was obtained by slow evaporation of the solvent from a mixture of 2,6-bis(trimethylsilyl)phosphinine selenide and 1,4-diiodotetrafluorobenzene (1,4-TFDIB). The crystallographic characterization of the product shows π-π stacking, F⋅⋅⋅H hydrogen bonding between 1,4-TFDIB and the phosphinine selenide, as well as F⋅⋅⋅F interactions between 1,4-TFDIB molecules. Moreover, the phosphorus heterocycle could be crystallized with diiodine to form a 1 : 1 adduct. The d distance in this compound is 2.8475(3) Å, which is shorter than the corresponding one in triphenylphosphine selenide diiodide, reflecting the weaker net-donor power of the phosphinine selenide towards diiodine. The phosphinine selenide could also be used as a selenium transfer reagent to generate KSeCN from KCN.
PubMed: 36229226
DOI: 10.1002/cplu.202200284 -
Ecotoxicology and Environmental Safety Oct 2022Hexavalent chromium [Cr (VI)] exists environmentally and occupationally. It has been shown to pose a carcinogenic hazard in certain occupations. This study was to...
Hexavalent chromium [Cr (VI)] exists environmentally and occupationally. It has been shown to pose a carcinogenic hazard in certain occupations. This study was to investigate the role of high mobility group A2 (HMGA2) in Cr (VI)-induced metabolism reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis in A549 and HELF cells. First, knockdown of HMGA2 by siHMGA2 significantly attenuated Cr (VI)-reduced expression of OXPHOS-related proteins (COX IV and ND1) and mitochondrial mass, indicating that HMGA2 was involved in Cr (VI)-reduced OXPHOS. Overexpression of HMGA2 by transfection of HMGA2-DNA plasmids reduced the expression of COX IV, ND1 and mitochondrial mass, suggesting the negative role of HMGA2 in OXPHOS. Secondly, both CCCP, the inhibitor of mitochondrial function, and the ER stress inhibitor, 4-phenylbutyric acid (4-PBA), decreased the level of HMGA2, indicating that the interaction of mitochondrial dysfunction and ER stress resulted in Cr (VI)-induced HMGA2 expression. Further study demonstrated that ER stress/HMGA2 axis mediated the metabolism rewiring from OXPHOS to aerobic glycolysis. Notably, Cr (VI) induced the accumulation of HMGA2 proteins in mitochondria and ChIP assay demonstrated that HMGA2 proteins could bind to D-loop region of mitochondrial DNA (mtDNA), which provided the proof for HMGA2-modulating OXPHOS. Taken together, our results suggested that the interaction of mitochondria and ER stress-enhanced HMGA2 played an important role in Cr (VI)-induced metabolic reprogramming from OXPHOS to glycolysis by binding directly to D-loop region of mtDNA. This work informs on the potential mode of action for Cr (VI)-induced tumors and builds on growing evidence regarding the contribution of cellular metabolic disruption contributing to carcinogenicity.
Topics: Carbonyl Cyanide m-Chlorophenyl Hydrazone; Chromium; DNA, Mitochondrial; Glycolysis; Mitochondria
PubMed: 36116352
DOI: 10.1016/j.ecoenv.2022.114085 -
Plant Disease Oct 2022As the excessive use of chemical fertilizers harms organisms and adversely affects the soil environment, the replacement of chemical fertilizers with biological...
As the excessive use of chemical fertilizers harms organisms and adversely affects the soil environment, the replacement of chemical fertilizers with biological fertilizers has attracted widespread attention as an environmental protection strategy. In this study, the effects of rhizosphere bacteria inoculation on growth of var. seedlings, soil parameters, soil microbial community structure, and the biocontrol of damping-off were studied by pot experiments. The results showed that all three rhizosphere bacteria (, , and A07) tested exhibited growth-promoting properties, such as the production of indole-3-acetic acid, hydrolase, siderophores, and hydrogen cyanide; nitrogen fixation; and phosphorus solubilization. The application of the three bacteria increased plant biomass, root structure, and nutrient content and also increased soil nutrient content and enzyme activity. Bacterial inoculation promoted the growth of beneficial bacteria and antagonistic bacteria by adjusting the physicochemical properties of the soil, thereby improving the bacterial community structure. Among the soil features, available nitrogen, total nitrogen, available potassium, and urease activity were the main influencing factors. In addition, it was also found that bacterial inoculation significantly increased the activities of plant superoxide dismutase, catalase, peroxidase, and other defense enzymes; enhanced plant disease resistance; effectively inhibited damping-off; and promoted plant growth. In summary, the application of three rhizosphere bacteria systematically affected the interaction between plants, soil parameters, and soil microbial communities. These results provide a basis for understanding how rhizosphere bacteria promote the growth of var. , thereby offering a promising sustainable alternative to chemical fertilizers.
Topics: Bacteria; Catalase; Fertilizers; Hydrogen Cyanide; Microbiota; Nitrogen; Phosphorus; Pinus sylvestris; Potassium; Rhizoctonia; Seedlings; Siderophores; Soil; Superoxide Dismutase; Urease
PubMed: 36094426
DOI: 10.1094/PDIS-11-21-2562-RE -
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 -
ACS Applied Materials & Interfaces Aug 2022Potassium ferricyanide in an aqueous solution is easily decomposed into highly toxic substances (potassium cyanide and hydrogen cyanide) by light or alkaline action,...
Potassium ferricyanide in an aqueous solution is easily decomposed into highly toxic substances (potassium cyanide and hydrogen cyanide) by light or alkaline action, which poses a major hazard to environmental and human health. Here, a reticulated aggregation-induced emission (AIE) supramolecular polymer material (TPAP-Mb@Q[14]) was prepared by the supramolecular self-assembly of twisted cucurbit[14]uril (Q[14]) and a triphenylamine derivative (TPAP-Mb). TPAP-Mb@Q[14] not only recognizes Fe(CN) with sensitive specificity with a limit of detection (LOD) of 1.64 × 10 M but can also effectively remove and adsorb Fe(CN) from an aqueous solution with a removal rate as high as 97.38%. Meanwhile, an important component of the supramolecular polymer material (Q[14]) can be reused. Thus, the Q[14]-based supramolecular assembly has the potential to be used for applications addressing toxic anionic contaminants present in aqueous environments.
PubMed: 35926157
DOI: 10.1021/acsami.2c10866