|
1
|
Kruithof PD, Lunev S, Aguilar Lozano SP, de Assis Batista F, Al-Dahmani ZM, Joles JA, Dolga AM, Groves MR, van Goor H. Unraveling the role of thiosulfate sulfurtransferase in metabolic diseases. Biochim Biophys Acta Mol Basis Dis 2020; 1866:165716. [PMID: 32061776 DOI: 10.1016/j.bbadis.2020.165716] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 01/10/2020] [Accepted: 01/30/2020] [Indexed: 02/08/2023]
Abstract
Thiosulfate sulfurtransferase (TST, EC 2.8.1.1), also known as Rhodanese, is a mitochondrial enzyme which catalyzes the transfer of sulfur in several molecular pathways. After its initial identification as a cyanide detoxification enzyme, it was found that its functions also include sulfur metabolism, modification of iron‑sulfur clusters and the reduction of antioxidants glutathione and thioredoxin. TST deficiency was shown to be strongly related to the pathophysiology of metabolic diseases including diabetes and obesity. This review summarizes research related to the enzymatic properties and functions of TST, to then explore the association between the effects of TST on mitochondria and development of diseases such as diabetes and obesity.
Collapse
Affiliation(s)
- Paul D Kruithof
- Univeristy of Groningen, Department of Pharmacy and Drug Design, the Netherlands
| | - Sergey Lunev
- Univeristy of Groningen, Department of Pharmacy and Drug Design, the Netherlands
| | | | | | - Zayana M Al-Dahmani
- Univeristy of Groningen, Department of Pharmacy and Drug Design, the Netherlands
| | - Jaap A Joles
- University Medical Center Utrecht, Department of Nephrology and Hypertension, the Netherlands
| | - Amalia M Dolga
- University of Groningen, Department of Pharmacy, Molecular Pharmacology, the Netherlands
| | - Matthew R Groves
- Univeristy of Groningen, Department of Pharmacy and Drug Design, the Netherlands
| | - Harry van Goor
- University Medical Center Groningen, Department of Pathology and Medical Biology the Netherlands.
| |
Collapse
|
|
2
|
Oh J, Jeon I, Kim D, You Y, Baek D, Kang SJ, Lee J. Highly Stable Upconverting Nanocrystal-Polydiacetylenes Nanoplates for Orthogonal Dual Signaling-Based Detection of Cyanide. ACS APPLIED MATERIALS & INTERFACES 2020; 12:4934-4943. [PMID: 31904923 DOI: 10.1021/acsami.9b20438] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Although the unique optical signaling properties of polydiacetylene (PDA) have been exploited in diverse bio-chemosensors, the practical application of most PDA sensor systems is limited by their instability in harsh environments and fluorescence signal weakness. Herein, a universal design principle for a highly stable PDA sensor system with a practical dual signaling capability is developed to detect cyanide (CN) ions, which are commonly found in drinking water. Effective metal intercalation and enhanced hydrophobic intermolecular interactions between PDA-metal supramolecules are used to construct highly stacked PDA-metal nanoplates that feature unusual optical stability upon exposure to strong acids, bases, organic solvents, and thermal/mechanical stresses, and can selectively detect CN anions, concomitantly undergoing a specific supramolecular structure change. To realize the practical dual signaling capability of the PDA sensor system, upconverting nanocrystals (UCNs) are incorporated into highly stacked PDA-metal nanoplates, and practical dual signaling (orthogonal changes in luminescence and visible color) is demonstrated using a portable detection system. The presented universal design principle is expected to be suitable for the development of other highly stable and selective PDA sensor systems with practical dual signaling capability.
Collapse
Affiliation(s)
- Jongwon Oh
- School of Energy and Chemical Engineering , Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919 , Republic of Korea
| | - Inkyu Jeon
- School of Energy and Chemical Engineering , Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919 , Republic of Korea
| | - Dowon Kim
- School of Energy and Chemical Engineering , Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919 , Republic of Korea
| | - Younghoon You
- School of Energy and Chemical Engineering , Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919 , Republic of Korea
| | - Dahye Baek
- School of Energy and Chemical Engineering , Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919 , Republic of Korea
| | - Seok Ju Kang
- School of Energy and Chemical Engineering , Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919 , Republic of Korea
| | - Jiseok Lee
- School of Energy and Chemical Engineering , Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919 , Republic of Korea
| |
Collapse
|
|
3
|
Identification of specific metabolic pathways as druggable targets regulating the sensitivity to cyanide poisoning. PLoS One 2018; 13:e0193889. [PMID: 29879736 PMCID: PMC5991913 DOI: 10.1371/journal.pone.0193889] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 02/20/2018] [Indexed: 11/19/2022] Open
Abstract
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.
Collapse
|
|
4
|
Petrikovics I, Budai M, Kovacs K, Thompson DE. Past, present and future of cyanide antagonism research: From the early remedies to the current therapies. World J Methodol 2015; 5:88-100. [PMID: 26140275 PMCID: PMC4482825 DOI: 10.5662/wjm.v5.i2.88] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 01/09/2015] [Accepted: 04/20/2015] [Indexed: 02/06/2023] Open
Abstract
This paper reviews milestones in antidotal therapies for cyanide (CN) spanning early remedies, current antidotal systems and research towards next generation therapies. CN has been a part of plant defense mechanisms for millions of years. It became industrially important in the nineteenth century with the advent of CN assisted gold mining and the use of CN as a pest control agent. The biochemical basis of CN poisoning was actively studied and key mechanisms were understood as early as 1929. These fundamental studies led to a variety of antidotes, including indirect CN binders that generate methemoglobin, direct CN binders such as hydroxocobalamin, and sulfur donors that convert CN to the less toxic thiocyanate. Research on blood gases at the end of the twentieth century shed new light on the role of nitric oxide (NO) in the body. The discovery of NO’s ability to compete with CN for enzymatic binding sites provided a previously missed explanation for the rapid efficacy of NO generating antidotes such as the nitrites. Presently used CN therapies include: methemoglobin/NO generators (e.g., sodium nitrite, amyl nitrite, and dimethyl aminophenol), sulfur donors (e.g., sodium thiosulfate and glutathione), and direct binding agents [(e.g., hydroxocobalamin and dicobalt salt of ethylenediaminetetraacetic acid (dicobalt edetate)]. A strong effort is being made to explore novel antidotal systems and to formulate them for rapid administration at the point of intoxication in mass casualty scenarios. New antidotes, formulations, and delivery systems are enhancing bioavailability and efficacy and hold promise for a new generation of improved CN countermeasures.
Collapse
|
|
5
|
Matusiewicz M, Kosieradzka I, Zuk M, Szopa J. Effect of Dose and Administration Period of Seed Cake of Genetically Modified and Non-Modified Flax on Selected Antioxidative Activities in Rats. Int J Mol Sci 2015; 16:14259-75. [PMID: 26110393 PMCID: PMC4490551 DOI: 10.3390/ijms160614259] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2015] [Revised: 06/11/2015] [Accepted: 06/12/2015] [Indexed: 02/07/2023] Open
Abstract
Flaxseed cake containing antioxidants is a valuable dietary component. Its nutritional effect may be diminished by the presence of anti-nutrients. The work was aimed at determining the effect of different contents of flaxseed cake in diets and their administration period on the development of rats and selected parameters of their health status. Diets with 15% and 30% addition of genetically modified (GM) flax seed cake with enhanced synthesis of polyphenols, as well as Linola non-GM flax were administered in short-term (33 days) and long-term (90 days) experiments. The 30% addition of flaxseed cake reduced digestibility of dietary nutrients, GM flaxseed cake lowered body weight gains. The relative weight of selected organs, hematological blood markers and serum activities of aspartate and alanine aminotransferases (AST, ALT) were not affected. Flaxseed cake consumption reduced serum concentration of albumins and increased globulins. Administration of 30% flaxseed cake improved plasma total antioxidant status and 30% GM flaxseed cake lowered liver thiobarbituric acid reactive substances. The activities of superoxide dismutase in erythrocytes, glutathione peroxidase in plasma and the liver concentration of 8-oxo-2′-deoxyguanosine were not changed. Most morphometric parameters of the small intestine did not differ between feeding groups. The administration of diets with 30% addition of flaxseed cake for 90 days improved the antioxidant status in rats.
Collapse
Affiliation(s)
- Magdalena Matusiewicz
- Department of Animal Nutrition and Biotechnology, Faculty of Animal Sciences, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786 Warsaw, Poland.
| | - Iwona Kosieradzka
- Department of Animal Nutrition and Biotechnology, Faculty of Animal Sciences, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786 Warsaw, Poland.
| | - Magdalena Zuk
- Department of Genetic Biochemistry, Faculty of Biotechnology, University of Wrocław, Przybyszewskiego 63/77, 51-148 Wrocław, Poland.
| | - Jan Szopa
- Department of Genetic Biochemistry, Faculty of Biotechnology, University of Wrocław, Przybyszewskiego 63/77, 51-148 Wrocław, Poland.
| |
Collapse
|
|
6
|
Chan A, Jiang J, Fridman A, Guo LT, Shelton GD, Liu MT, Green C, Haushalter KJ, Patel HH, Lee J, Yoon D, Burney T, Mukai D, Mahon SB, Brenner M, Pilz RB, Boss GR. Nitrocobinamide, a new cyanide antidote that can be administered by intramuscular injection. J Med Chem 2015; 58:1750-9. [PMID: 25650735 DOI: 10.1021/jm501565k] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Currently available cyanide antidotes must be given by intravenous injection over 5-10 min, making them ill-suited for treating many people in the field, as could occur in a major fire, an industrial accident, or a terrorist attack. These scenarios call for a drug that can be given quickly, e.g., by intramuscular injection. We have shown that aquohydroxocobinamide is a potent cyanide antidote in animal models of cyanide poisoning, but it is unstable in solution and poorly absorbed after intramuscular injection. Here we show that adding sodium nitrite to cobinamide yields a stable derivative (referred to as nitrocobinamide) that rescues cyanide-poisoned mice and rabbits when given by intramuscular injection. We also show that the efficacy of nitrocobinamide is markedly enhanced by coadministering sodium thiosulfate (reducing the total injected volume), and we calculate that ∼1.4 mL each of nitrocobinamide and sodium thiosulfate should rescue a human from a lethal cyanide exposure.
Collapse
Affiliation(s)
- Adriano Chan
- Departments of †Medicine, ‡Pathology, §Chemistry and Biochemistry, and ∥Anesthesiology, University of California-San Diego , La Jolla, California 92093-0652, United States
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
7
|
Zottola MA, Beigel K, Soni SD, Lawrence R. Disulfides as Cyanide Antidotes: Evidence for a New In Vivo Oxidative Pathway for Cyanide Detoxification. Chem Res Toxicol 2009; 22:1948-53. [DOI: 10.1021/tx900258m] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Mark A. Zottola
- United States Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Edgewood Area-Aberdeen Proving Ground, Maryland 21010, and Department of Chemistry, University of Alabama at Birmingham, 1530 Third Avenue South, Birmingham, Alabama 35294
| | - Keith Beigel
- United States Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Edgewood Area-Aberdeen Proving Ground, Maryland 21010, and Department of Chemistry, University of Alabama at Birmingham, 1530 Third Avenue South, Birmingham, Alabama 35294
| | - Sunil-Datta Soni
- United States Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Edgewood Area-Aberdeen Proving Ground, Maryland 21010, and Department of Chemistry, University of Alabama at Birmingham, 1530 Third Avenue South, Birmingham, Alabama 35294
| | - Richard Lawrence
- United States Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Edgewood Area-Aberdeen Proving Ground, Maryland 21010, and Department of Chemistry, University of Alabama at Birmingham, 1530 Third Avenue South, Birmingham, Alabama 35294
| |
Collapse
|
|
8
|
Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) on hydrocyanic acid in flavourings and other food ingredients with flavouring properties. EFSA J 2004. [DOI: 10.2903/j.efsa.2004.105] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
|
|
9
|
Wing D, Patel H, Baskin S. The effect of picrylsulphonic acid on In vitro conversion of cyanide to thiocyanate by 3-mercaptopyruvate sulphurtransferase and rhodanese. Toxicol In Vitro 1992; 6:597-603. [DOI: 10.1016/0887-2333(92)90073-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/1992] [Revised: 04/07/1992] [Indexed: 10/27/2022]
|
|
10
|
Brittebo EB, Eriksson C, Brandt I. Effects of glutathione-modulating agents on the covalent binding and toxicity of dichlobenil in the mouse olfactory mucosa. Toxicol Appl Pharmacol 1992; 114:31-40. [PMID: 1585372 DOI: 10.1016/0041-008x(92)90093-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Twenty-four hours following injection of a single dose of the herbicide dichlobenil (2,6-dichlorobenzonitrile) in C57Bl/6 mice a steep dose-response curve for the histopathological toxicity in the olfactory mucosa was observed. Four hours following injection of a toxic dose of [ring-14C]dichlobenil (12 mg/kg) the covalent binding in the olfactory mucosa was 26 times higher than that in the liver. A dose-dependent decrease of nonprotein sulfhydryls (mainly glutathione, GSH) in the olfactory mucosa was observed 2.5 hr following injection of dichlobenil (6, 12, 25 mg/kg). The synthetic GSH precursor N-acetyl-L-cysteine decreased both the dichlobenil-induced toxicity and the covalent binding, whereas N-acetyl-D-cysteine had no effect. No protective effects of the cyanide antidotes nitrite, thiosulfate, or superoxide dismutase on the dichlobenil-induced toxicity were observed. In mice given the GSH-depleting agent phorone and a subtoxic dose of dichlobenil (6 mg/kg), an extensive toxicity and an increased covalent binding in the olfactory mucosa were demonstrated. Autoradiography showed no change in the distribution of covalent [14C]dichlobenil binding to nontarget tissues of phorone-treated mice. In conclusion, the results demonstrate a relationship between the degrees of covalent binding, GSH depletion, and toxicity of dichlobenil in the olfactory mucosa. Hence, the level of GSH appears to be of importance for the dichlobenil-induced toxicity in the olfactory mucosa.
Collapse
Affiliation(s)
- E B Brittebo
- Department of Pharmacology and Toxicology, SLU, Uppsala, Sweden
| | | | | |
Collapse
|
|
11
|
Sylvester M, Sander C. Immunohistochemical localization of rhodanese. THE HISTOCHEMICAL JOURNAL 1990; 22:197-200. [PMID: 2387754 DOI: 10.1007/bf02386005] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The role of rhodanese in the detoxication of acute cyanide exposure is controversial. The debate involves questions of the availability of rhodanese to cyanide in the peripheral circulation. Blood-borne cyanide will distribute to the brain and may induce lesions or even death. The present study addresses the dispute by determining the distribution of rhodanese in tissues considered to have the highest rhodanese activity and thought to serve as major detoxication sites. The results indicate that rhodanese levels are highest in (1) hepatocytes that are in close proximity to the blood supply of the liver (2) epithelial cells surrounding the bronchioles (a major entry route for gaseous cyanide) and (3) proximal tubule cells of the kidney (serving to facilitate cyanide detoxication and elimination as thiocyanate). Rhodanese activity in the brain is low compared with liver and kidney (Mimori et al., 1984; Drawbaugh & Marrs, 1987); the brain is not considered to be a major site of cyanide detoxication. The brain, however, is the target for cyanide toxicity. In this study our goal was also to differentiate the distribution of rhodanese in an area of the brain. We found that the enzyme level is highest in fibrous astrocytes of the white matter. Cyanide-induced brain lesions may thus occur in areas of the brain lacking sufficient sites for detoxication.
Collapse
Affiliation(s)
- M Sylvester
- Pharmacology-Toxicology Graduate Programme, College of Pharmacy, Washington State University, Pullman 99164-6510
| | | |
Collapse
|
|
12
|
Abstract
Isolated hepatocyte systems are being examined in our laboratory for a number of applications, including alternatives to animal testing. This report summarizes findings from studies with chlorinated aliphatics, acetaminophen, nitrotoluenes, and cyanide and its antidotes that relate to in vivo toxicity and validation of these systems for cytotoxicity screening.
Collapse
Affiliation(s)
- C A Tyson
- SRI International, Menlo Park, CA 94025
| |
Collapse
|
|
13
|
Gee SJ, LeValley SE, Tyson CA. Application of a hepatocyte-erythrocyte coincubation system to studies of cyanide antidotal mechanisms. Toxicol Appl Pharmacol 1987; 88:24-34. [PMID: 3564031 DOI: 10.1016/0041-008x(87)90266-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
A coincubation system composed of hepatocytes in primary monolayer culture and erythrocytes suspended in the culture medium was developed and used as a model for investigations of mechanisms of cyanide antidote action at the cellular level. Hepatocyte ATP was used as the cytotoxicity indicator. Treatment of rat hepatocytes in the coincubation system with KCN (1.0 mM) for 10 min at 37 degrees C selectively reduced hepatocyte ATP levels to 33 +/- 15% of control (no KCN added) levels. 4-dimethylaminophenol (DMAP), cobalt(II) chloride, sodium nitrite, sodium thiosulfate, or a combination of the last two antidotes added to the KCN-containing medium significantly reversed ATP depression and the response was concentration dependent. The relative effectiveness, on a molar basis, was estimated to be DMAP greater than CoCl2 much greater than NaNO2 congruent to Na2S2O3. NaNO2 and DMAP induced methemoglobin formation in the absence of cyanide and cyanmethemoglobin formation in its presence; erythrocytes were required in the medium for effectiveness. CoCl2 produced neither cyanmethemoglobin nor thiocyanate in appreciable quantities nor required erythrocytes for antagonism. Na2S2O3 converted cyanide to thiocyanate and reversed ATP depression without erythrocytes in the medium. The addition of erythrocytes increased these rates significantly and to a greater extent than albumin. The overall results are consistent with previously proposed modes of action for these antidotes. However, the enhancement in cyanide metabolism and ATP recovery with Na2S2O3 and erythrocytes in the system was unexpected and raises the possibility that erythrocytes may contribute to cyanide disposition and antagonism in vivo when this antidote is administered.
Collapse
|
|
14
|
Ten Eyck RP, Schaerdel AD, Ottinger WE. Stroma-free methemoglobin solution: an effective antidote for acute cyanide poisoning. Am J Emerg Med 1985; 3:519-23. [PMID: 4063017 DOI: 10.1016/0735-6757(85)90163-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Several aspects of stroma-free methemoglobin solution (SFMS) as a cyanide antidote were investigated using a rat model. Stroma-free methemoglobin solution was more than 90% effective against multiples of the LD90 of cyanide up to and including four times the LD90 and approximately 50% effective against multiples up to and including eight times the LD90. Highly concentrated solutions of SFMS (33 g/dl) did not differ significantly from less concentrated solutions of SFMS (16 g/dl) when compared on the basis of efficacy. Administration of large doses of SFMS alone resulted in no apparent morbidity or mortality. It could be that SFMS is a safe and effective alternative antidote for the treatment of cyanide poisoning.
Collapse
|
|
15
|
Effect of cyanide on the distribution of 60Co in mice. Arch Toxicol 1982. [DOI: 10.1007/bf00302753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
16
|
Marbury TC, Sheppard JE, Gibbons K, Lee CS. Combined antidotal and hemodialysis treatments for nitroprusside-induced cyanide toxicity. JOURNAL OF TOXICOLOGY. CLINICAL TOXICOLOGY 1982; 19:475-82. [PMID: 7175992 DOI: 10.3109/15563658208992502] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
A case report is presented for a patient with nitroprusside-induced cyanide intoxication. The patient received approximately 1 g sodium nitroprusside through an intravenous infusion of the drug over 6 d. The toxicity was treated with antidotes, sodium nitrite and sodium thiosulfate, followed by hemodialysis. Hemodialysis significantly removed thiocyanate but not cyanide from the patient's extracorporeal circulation. The removal of thiocyanate by hemodialysis enhanced the liberation of cyanide from the cytochrome oxidase. Hemodialysis is a significant addition to the therapy of cyanide toxicity, particularly for intoxicated patient with reduced renal function
Collapse
|
|
17
|
Clark CR, Wall GM, Davidson PP. Acute toxicity of some alkylaminocyclohexane carbonitriles, probable contaminants of phencyclidine analogs. J Appl Toxicol 1982. [DOI: 10.1002/jat.2550020104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
|
|
18
|
Abstract
In recent years, the increasing use of laetrile has been added to the traditional sources of exposure to cyanide in industry, chemistry labs, and fumigation. The events in Jonestown in 1978 were a grim reminder of the lethality of cyanide. Nonetheless, advancement in new modes of treatment has been slow. The traditional method of treatment used in the United States is effective, but not without its own morbidity and mortality. Using two case reports as models, we review here the topic of cyanide poisoning including sources of exposure, pathophysiology, clinical manifestations of both acute and chronic exposure, and modes of treatment. Although there is currently no accepted alternate treatment in this country, review of the literature shows promise in other modalities being investigated in Europe, including hydroxocobalamin, cobalt salts, and particularly aminophenols.
Collapse
|
|
19
|
|
|
20
|
Christel D, Eyer P, Hegemann M, Kiese M, Lörcher W, Weger N. Pharmacokinetics of cyanide in poisoning of dogs, and the effect of 4-dimethylaminophenol or thiosulfate. Arch Toxicol 1977; 38:177-89. [PMID: 578721 DOI: 10.1007/bf00293652] [Citation(s) in RCA: 43] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Cyanide in blood, plasma, and urine of dogs after administration of K14CN was determined with the isotope dilution technique. The addition of large amounts of inactive KCN as soon as possible to a sample to be analyzed inhibited the decrease of the original cyanide concentration. After administration of several lethal doses of cyanide into the stomach or by slow intravenous infusion a concentration of about 40 micron cyanide in plasma was found at the moment of respiratory arrest. Since 60% of the cyanide in plasma was bound to proteins the concentration of free cyanide which stopped respiration was about 16 micron. Quick formation of ferrihemoglobin by i.v. injection of 4-dimethylaminophenol after plasma cyanide had risen to or above 40 micron decreased the cyanide concentration in plasma and restored respiration, while cyanide was accumulated in red cells by formation of ferrihemoglobin cyanide. Equilibrium constants calculated for the reaction between ferrihemoglobin and cyanide in vivo indicated that the reaction approached equilibrium in a few minutes. Up to 60% of the radioactive cyanide absorbed was found as non-cyanide radioactivity in the urine.
Collapse
|
|
21
|
Bogusz M. Disappearance of cyanide in blood and tissues after fatal poisoning. FORENSIC SCIENCE 1976; 7:173. [PMID: 964809 DOI: 10.1016/0300-9432(76)90034-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
|