- Characterization of a Swine (Sus scrofa) Model of Oral Potassium Cyanide Intoxication. [Journal Article]
- CMComp Med 2018 Sep 12
- Cyanide is a readily available and potentially lethal substance. Oral exposure can result in larger doses, compared withother routes. Currently, there are no antidotes specific for use in the treatme...
Cyanide is a readily available and potentially lethal substance. Oral exposure can result in larger doses, compared withother routes. Currently, there are no antidotes specific for use in the treatment of oral cyanide poisoning, and studies cannotbe done in humans. We report on a new large animal model of oral cyanide toxicity to evaluate potential antidotes. Six femaleswine (Sus scrofa; weight, 45 to 55 kg) were anesthetized, intubated, and instrumented. Animals received a KCN bolusof either 5 or 8 mg/kg delivered via orogastric tube. Time to apnea was recorded; parameters monitored included heart rate,respiratory rate, blood pressure, pulse oximetry, end-tidal CO2, arterial blood gasses, and lactate concentrations. The Welcht test was used to calculate confidence intervals, mean, and standard deviation, and a Kaplan-Meier survival curve was usedto compare survival between the 2 groups. At baseline, all animals in both groups were similar. Animals in the 5-mg/kg grouphad a more rapid time to apnea (5.1 ± 2.1 min), longer time to death (48.5 ± 38.1 min), and a greater rate of survival than the8-mg/kg group (apnea, 10.6 ± 10.7 min; death, 26.1 ± 5.8 min). All animals displayed signs of toxicity (acidemia, hyperlactatemia,hypotension, apnea). We here report a large animal (swine) model of oral cyanide poisoning with dose-dependent effects in regard to time to death and survival rate. This model likely will be valuable for the development of medical countermeasures for oral cyanide poisoning.
- Protective efficacy of various carbonyl compounds and their metabolites, and nutrients against acute toxicity of some cyanogens in rats: biochemical and physiological studies. [Journal Article]
- ITInterdiscip Toxicol 2017; 10(1):1-10
- Cyanogens are widely used in industries and their toxicity is mainly due to cyanogenesis. The antidotes for cyanide are usually instituted for the management of cyanogen poisoning. The present study ...
Cyanogens are widely used in industries and their toxicity is mainly due to cyanogenesis. The antidotes for cyanide are usually instituted for the management of cyanogen poisoning. The present study reports the protective efficacy of 14 carbonyl compounds and their metabolites, and nutrients (1.0 g/kg; oral; +5 min) against acute oral toxicity of acetonitrile (ATCN), acrylonitrile (ACN), malononitrile (MCN), propionitrile (PCN), sodium nitroprusside (SNP), succinonitrile (SCN), and potassium ferricyanide (PFCN) in rats. Maximum protection index was observed for alpha-ketoglutarate (A-KG) against MCN and PCN (5.60), followed by dihydroxyacetone (DHA) against MCN (2.79). Further, MCN (0.75 LD50) caused significant increase in cyanide concentration in brain, liver and kidney and inhibition of cytochrome c oxidase activity in brain and liver, which favorably responded to A-KG and DHA treatment. Up-regulation of inducible nitric oxide synthase by MCN, PCN and SNP, and uncoupling protein by PCN and SNP observed in the brain was abolished by A-KG administration. However, no DNA damage was detected in the brain. MCN and SNP significantly decreased the mean arterial pressure, heart rate, respiratory rate and neuromuscular transmission, which were resolved by A-KG. The study suggests a beneficial effect of A-KG in the treatment of acute cyanogen poisoning.
- Identification of specific metabolic pathways as druggable targets regulating the sensitivity to cyanide poisoning. [Journal Article]
- PlosPLoS One 2018; 13(6):e0193889
- Cyanide is a potent toxic agent, and the few available antidotes are not amenable to rapid deployment in mass exposures. As a result, there are ongoing efforts to exploit different animal models to i...
Cyanide is a potent toxic agent, and the few available antidotes are not amenable to rapid deployment in mass exposures. As a result, there are ongoing efforts to exploit different animal models to identify novel countermeasures. We have created a pipeline that combines high-throughput screening in zebrafish with subsequent validation in two mammalian small animal models as well as a porcine large animal model. We found that zebrafish embryos in the first 3 days post fertilization (dpf) are highly resistant to cyanide, becoming progressively more sensitive thereafter. Unbiased analysis of gene expression in response to several hours of ultimately lethal doses of cyanide in both 1 and 7 dpf zebrafish revealed modest changes in iron-related proteins associated with the age-dependent cyanide resistance. Metabolomics measurements demonstrated significant age-dependent differences in energy metabolism during cyanide exposure which prompted us to test modulators of the tricarboxylic acid cycle and related metabolic processes as potential antidotes. In cyanide-sensitive 7 dpf larvae, we identified several such compounds that offer significant protection against cyanide toxicity. Modulators of the pyruvate dehydrogenase complex, as well as the small molecule sodium glyoxylate, consistently protected against cyanide toxicity in 7 dpf zebrafish larvae. Together, our results indicate that the resistance of zebrafish embryos to cyanide toxicity during early development is related to an altered regulation of cellular metabolism, which we propose may be exploited as a potential target for the development of novel antidotes against cyanide poisoning.
- An insoluble iron complex coated cathode enhances direct electron uptake by Rhodopseudomonas palustris TIE-1. [Journal Article]
- BBioelectrochemistry 2018; 122:164-173
- Microbial electrosynthesis (MES) is a promising bioelectrochemical approach to produce biochemicals. A previous study showed that Rhodopseudomonas palustris TIE-1 can directly use poised electrodes a...
Microbial electrosynthesis (MES) is a promising bioelectrochemical approach to produce biochemicals. A previous study showed that Rhodopseudomonas palustris TIE-1 can directly use poised electrodes as electron donors for photoautotrophic growth at cathodic potentials that avoid electrolytic H2 production (photoelectroautotrophy). To make TIE-1 an effective biocatalyst for MES, we need to improve its electron uptake ability and growth under photoelectroautotrophic conditions. Because TIE-1 interacts with various forms of iron while using it as a source of electrons for photoautotrophy (photoferroautotrophy), we tested the ability of iron-based redox mediators to enhance direct electron uptake. Our data show that soluble iron cannot act as a redox mediator for electron uptake by TIE-1 from a cathode poised at +100mV vs. Standard Hydrogen electrode. We then tested whether an immobilized iron-based redox mediator Prussian blue (PB) can enhance electron uptake by TIE-1. Chronoamperometry indicates that cathodic current uptake by TIE-1 increased from 1.47±0.04 to 5.6±0.09μA/cm2 (3.8 times). Overall, our data show that immobilized PB can enhance direct electron uptake by TIE-1.
- On the Efficacy of Cardio-Pulmonary Resuscitation and Epinephrine Following Cyanide- and H2S Intoxication-Induced Cardiac Asystole. [Journal Article]
- CTCardiovasc Toxicol 2018 Apr 11
- This study was aimed at determining the efficacy of epinephrine, followed by chest compressions, in producing a return of spontaneous circulation (ROSC) during cyanide (CN)- or hydrogen sulfide (H2S)...
This study was aimed at determining the efficacy of epinephrine, followed by chest compressions, in producing a return of spontaneous circulation (ROSC) during cyanide (CN)- or hydrogen sulfide (H2S)-induced toxic cardiac pulseless electrical activity (PEA) in the rat. Thirty-nine anesthetized rats were exposed to either intravenous KCN (n = 27) or H2S solutions (n = 12), at a rate that led to a PEA within less than 10 min. In the group intoxicated by CN, 20 rats were mechanically ventilated and received either epinephrine (0.1 mg/kg i.v. n = 10) followed by chest compressions or saline (n = 10, "control CN") when in PEA. PEA was defined as a systolic pressure below 20 mmHg and a pulse pressure of less than 5 mmHg for 1 min. In addition, seven spontaneously breathing rats were also exposed to the same CN protocol, but infusion was stopped when a central apnea occurred; then, as soon as a PEA occurred, epinephrine (0.1 mg/kg IV) was administered while providing manual chest compressions and mechanical ventilation (CPR). Finally, 12 rats were intoxicated with H2S, while mechanically ventilated, and received either saline (n = 6, "control H2S") or epinephrine (n = 6) with CPR when in PEA. None of the control-intoxicated animals resuscitated (10 rats in the control CN group and 6 in the control H2S group). In contrast, all the animals intoxicated with CN or H2S that received epinephrine followed by chest compressions, returned to effective circulation. In addition, half of the spontaneously breathing CN-intoxicated animals that achieved ROSC after epinephrine resumed spontaneous breathing. In all the animals achieving ROSC, blood pressure, cardiac output, peripheral blood flow and [Formula: see text]O2 returned toward baseline, but remained lower than the pre-intoxication levels (p < 0.01) with a persistent lactic acidosis. Epinephrine, along with CPR maneuvers, was highly effective in resuscitating rodents intoxicated with CN or H2S. Since epinephrine is readily available in any ambulance, its place as an important countermeasure against mitochondrial poisons should be advocated. It remains critical to determine whether the systematic administration of epinephrine to any victims found hypotensive following CN or H2S intoxication could prevent PEA, decrease post-ischemic brain injury and increase the efficacy of current antidotes by improving the circulatory status.
- Assessing the efficacy of aqueous garlic extract, sodium nitrite and sodium thiosulfate against prolonged oral cyanide exposure in rabbits. [Journal Article]
- PJPak J Pharm Sci 2018; 31(2):411-419
- This study was aimed to compare the efficacy of aqueous garlic extract, sodium nitrite (SNT), sodium thiosulfate (STS) and hydroxocobalamin against oral cyanide exposure in rabbits. For this purpose,...
This study was aimed to compare the efficacy of aqueous garlic extract, sodium nitrite (SNT), sodium thiosulfate (STS) and hydroxocobalamin against oral cyanide exposure in rabbits. For this purpose, forty two adult male rabbits were divided randomly into 7 groups of 6 animals (A-G) each. Rabbits in group A were offered feed only and served as negative control, while the rabbits in group B received feed plus potassium cyanide (KCN) at 3mg/kg orally and were kept as positive control. Animals in group C received feed, KCN and intraperitoneal injection (IP) of aqueous garlic extract at 500mg/kg. Rabbits in group D were given feed, KCN and IP injection of STS at 600mg/kg. Members in group E received feed, KCN and IP injection of both aqueous garlic extract at 500mg/kg and SNT at 20mg/kg. Animals in group F were given feed, KCN and IP injection of both STS at 600mg/kg and SNT at 20mg/kg, while the rabbits in group G received feed, KCN and IP injection of hydroxocobalamin at 300mg/kg. The treatments were given to respective groups for 40 days. The efficacy of the antidotes was measured on the basis of changes in biochemical profile of rabbits in each group. In this study, hydroxocobalamin was found to be significantly more effective cyanide (CNI) antidote than garlic, STS, SNT plus garlic extract, or SNT and STS, either alone or in combination. A combination of SNT and garlic extract was the second most effective CNI antidote. The efficacy of garlic alone was significantly higher than STS alone or in combination with SNT. The efficacy of combined SNT and STS was superior to STS alone in treating rabbits with CNI toxicity. In conclusion, aqueous garlic extract alone or in combination with STS can effectively be used against cyanide toxicity.
- Enhanced cesium removal from real matrices by nickel-hexacyanoferrate modified activated carbons. [Journal Article]
- CChemosphere 2018; 202:569-575
- After nuclear disasters, radioactive cesium partitions to soils and surface water, where it decays slowly. Hexacyanoferrates (HCFs) have excellent cesium removal properties but their structure is typ...
After nuclear disasters, radioactive cesium partitions to soils and surface water, where it decays slowly. Hexacyanoferrates (HCFs) have excellent cesium removal properties but their structure is typically powdery. Many carrier materials, such as biomass or magnetic particles, have been used to provide a suitable substrate for HCFs that can be used in filters. This research uses the sorption properties of activated carbon (AC) to incorporate Ni-HCF, resulting in good structural properties of the hybrid material. These HCF-modified ACs show drastically improved sorption properties towards Cs after one, two and three HCF impregnation cycles. The activated carbon from brewer's spent grain with one modification cycle removes more than 80% of 1 mg L-1 Cs in a sea water solution and more than 98% of 1 mg L-1 Cs from surface water at a low AC dosage (0.5 g L-1). Iron and nickel leaching is studied and found to be dependent on the type of modified AC used and the leaching solution. Iron leaching can be problematic in surface and seawater, whereas nickel leaching is especially pronounced in seawater.
- A Comparison of the Cyanide-Scavenging Capabilities of Some Cobalt-Containing Complexes in Mice. [Journal Article]
- CRChem Res Toxicol 2018 Apr 16; 31(4):259-268
- Four cobalt-containing macrocyclic compounds previously shown to ameliorate cyanide toxicity have been comparatively evaluated with an acute sublethal toxicity model in conscious (unanesthetized) adu...
Four cobalt-containing macrocyclic compounds previously shown to ameliorate cyanide toxicity have been comparatively evaluated with an acute sublethal toxicity model in conscious (unanesthetized) adult male Swiss-Webster mice. All of the compounds (the cobalt-corrins cobalamin and cobinamide, a cobalt-porphyrin, plus a cobalt-Schiff base macrocycle) given 5 min prior to the toxicant dose significantly decreased the righting-recovery time of cyanide-intoxicated mice, but the doses required for maximal antidotal effect varied. Additionally, all of the compounds tested significantly reduced the righting-recovery time when administered at either 1 or 2 min after cyanide intoxication, but none of the compounds tested significantly reduced the righting-recovery time when delivered 5 min after the toxicant dose. Using the lowest effective dose of each compound determined during the first (prophylactic) set of experiments, neuromuscular recovery following cyanide intoxication in the presence/absence of the cobalt-based antidotes was assessed by RotaRod testing. All the compounds tested accelerated recovery of neuromuscular coordination, and no persistent impairment in any group, including those animals that received toxicant and no antidote, was apparent up to 2 weeks postexposures. The relative effectiveness of the cobalt compounds as cyanide antidotes are discussed and rationalized on the basis of the cyanide-binding stoichiometries and stability constants of the Co(III) cyano adducts, together with consideration of the rate constants for axial ligand substitutions by cyanide in the Co(II) forms.
- Sparks fly between ascorbic acid and iron-based nanozymes: A study on Prussian blue nanoparticles. [Journal Article]
- CSColloids Surf B Biointerfaces 2018 Mar 01; 163:379-384
- Herein we reported Prussian blue nanoparticles (PBNPs) possess ascorbic acid oxidase (AAO)- and ascorbic acid peroxidase (APOD)-like activities, which suppressed the formation of harmful H2O2 and fin...
Herein we reported Prussian blue nanoparticles (PBNPs) possess ascorbic acid oxidase (AAO)- and ascorbic acid peroxidase (APOD)-like activities, which suppressed the formation of harmful H2O2 and finally inhibited the anti-cancer efficiency of ascorbic acid (AA). This newly revealed correlation between iron and AA could provide new insight for the studies of nanozymes and free radical biology.
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- Direct Synthesis of Prussian Blue Nanoparticles in Liposomes Incorporating Natural Ion Channels for Cs+ Adsorption and Particle Size Control. [Journal Article]
- LLangmuir 2018 01 30; 34(4):1666-1672
- Coordination polymer (CP) nanoparticles (NPs) formed by a self-assembly of organic ligands and metal ions are one of the attractive materials for molecular capture and deliver/release in aqueous medi...
Coordination polymer (CP) nanoparticles (NPs) formed by a self-assembly of organic ligands and metal ions are one of the attractive materials for molecular capture and deliver/release in aqueous media. Control of particle size and prevention of aggregation among CP NPs are important factors for improving their adsorption capability in water. We demonstrate here the potential of a liposome incorporating an antibiotic ion channel as a vessel for synthesizing Prussian blue (PB) NPs, being a typical CP. In the formation of PB NPs within liposomes, the influx rate of Fe2+ ions into liposome encapsulated [Fe(CN)6]3- through channels was fundamental for the change of NPs' sizes. The optimized PB NP-liposome composite showed higher adsorption capacity of Cs+ ions than that of aggregated PB NPs that are prepared without liposome in aqueous media.