Cyanide intoxication-I. An oral chronic animal model

The effects of oral chronic cyanide administration to mice were studied. Cyanide intoxication was confirmed by the increased levels of this poison and the concomitant inhibition of cytochrome oxidase activity in liver, brain, heart and blood. The detoxifying enzyme rhodanese was measured. The state...

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Autor principal: Buzaleh, A.M
Otros Autores: Vazquez, E.S, Del Battle, C.A.M
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 1989
Acceso en línea:Registro en Scopus
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024 7 |2 scopus  |a 2-s2.0-0024604682 
024 7 |2 cas  |a cyanide, 57-12-5; cytochrome c oxidase, 72841-18-0, 9001-16-5; thiocyanate, 302-04-5; thiosulfate sulfurtransferase, 9026-04-4; Cyanides; Cytochrome-c Oxidase, EC 1.9.3.1; Proteins; Sulfur, 7704-34-9; Thiocyanates; Thiosulfate Sulfurtransferase, EC 2.8.1.1 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a GEPHD 
100 1 |a Buzaleh, A.M. 
245 1 0 |a Cyanide intoxication-I. An oral chronic animal model 
260 |c 1989 
270 1 0 |m del C. Batlle, A.M.; Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Facultad de Ciencias Exactas y Naturales, 1448 Buenos Aires, Argentina 
506 |2 openaire  |e Política editorial 
504 |a Albaum, Tepperman, Bodansky, The in vivo inactivation by cyanide of brain cytochrome oxidase and its effect on glycolysis and on the high energy phosphorous compounds in brain (1946) J Biol Chem, 164, pp. 45-51 
504 |a Ballantyne, Artifacts in the definition of toxicity by cyanides and cyanogens (1983) Fundamental and Applied Toxicology, 3, pp. 400-408 
504 |a Boxer, Rickards, Studies on the metabolism of the carbon of cyanide and thiocyanate (1952) Arch. Biochem., 39, pp. 7-12 
504 |a Finazzi Agró, Federici, Giovagnoli, Cannella, Cavallini, Effect of sulfur binding on rhodanese fluourescence (1972) European Journal of Biochemistry, 28, pp. 89-93 
504 |a Guilbault, Kramer, Specific detection and determination of cyanide using various quinone derivatives (1965) Analytical Chemistry, 37, pp. 1395-1400 
504 |a Himwich, Saunders, Enzymatic conversion of cyanide to thiocyanate (1948) Am. J. Physiol., 153, pp. 348-354 
504 |a Isom, Way, Lethality of cyanide in the absence of inhibition of liver cytochrome oxidase (1976) Biochem. Pharmac., 25, pp. 605-608 
504 |a Isom, Burrows, Way, Effect of oxygen on the antagonism of cyanide intoxication (1982) Cytochrome oxidase in vivo, 65, pp. 250-256. , Tox. appl. Pharmac 
504 |a Koh, The determination of micro amounts of polythionates I A photometric method for the determination of pentathionate by means of its cyanolysis (1965) Bulletin of the Chemical Society of Japan, 38, pp. 1510-1515 
504 |a Lowry, Rosebrough, Farr, Randall, Protein measurement with the Folin-Phenol reagent (1951) J. biol. Chem., 193, pp. 265-275 
504 |a Schubert, Brill, Antagonism of experimental cyanide toxicity in relation to the in vivo activity of cytochrome oxidase (1968) J. Pharmac. exp. Ther., 162, pp. 352-359 
504 |a Solomonson, (1982) Cyanide in Biology, pp. 11-28. , Academic Press, London 
504 |a Sörbo, Crystalline rhodanese I Purification and physico-chemical examination (1953) Acta Chemica Scandinavica, 7, pp. 1129-1136 
504 |a Vázquez, Buzaleh, Wider, Batlle, Red blood cell rhodanese: its possible role in modulating δ-aminolevulinate synthetase activity in mammals (1987) Int. J. Biochem., 19, pp. 217-219 
504 |a Vennesland, Castic, Conn, Solomonson, Volini, Westley, Cyanide metabolism (1982) Fedn Proc., 41, pp. 2639-2648 
504 |a Way, Cyanide intoxication and its mechanism of antagonism (1984) A. Rev. Pharmac. Tox., 24, pp. 451-481 
504 |a Westley, Adler, Westley, Nishida, The sulfur-transferases (1983) Fundamental and Applied Toxicology, 3, pp. 377-382 
504 |a Wilson, Cyanide in human diseases a review of clinical and laboratory evidence (1983) Fundamental and Applied Toxicology, 3, pp. 397-399 
504 |a Wood, Cooley, Detoxification of cyanide by cystine (1956) J Biol Chem, 218, pp. 449-457 
504 |a Yonetani, Ray, Studies on cytochrome oxidase VI. Kinetics of the aerobic oxidation of ferrocytochrome c by cytochrome oxidase (1965) J. biol. Chem., 240, pp. 3392-3398 
520 3 |a The effects of oral chronic cyanide administration to mice were studied. Cyanide intoxication was confirmed by the increased levels of this poison and the concomitant inhibition of cytochrome oxidase activity in liver, brain, heart and blood. The detoxifying enzyme rhodanese was measured. The state of the sulfane sulfur pool was investigated by determination of the cyanide labile-sulfur levels. A clear correlation between rhodanese activity and sulfur content was obtained as a consequence of cyanide action. These results support the belief that rhodanese plays a fundamental role in the detoxification process of cyanide, in preventing cyanide reaching the target tissues. © 1989.  |l eng 
536 |a Detalles de la financiación: Universidad de Buenos Aires 
536 |a Detalles de la financiación: Secretaria de Ciencia y Tecnica, Universidad de Buenos Aires 
536 |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas 
536 |a Detalles de la financiación: The results obtained indicate that an animal model for chronic cyanide intoxication can be produced by oral administration of the toxin to mice. Under the conditions described, cyanide intoxication was demonstrated by the high levels of cyanide accumulated in organs and blood, as well as by the corresponding inhibition of cytochrome oxidase activity; although it should be considered that the degree of inhibition in tissue homogenates may not be an accurate reflection of the situation in rive (Ballantyne, 1983). The fact that rhodanese activity was detectable even without adding cyanide to the incubation mixture, is also indicative of the presence of the toxin in these tissues• The diminished activity of liver rhodanese could be attributed to the high levels of cyanide in the tissue; this effect would be magnified by the lower hepatic levels of labile sulfur measured which would reduce the degree of conversion of rhodanese to its active sulfur substituted form (Finazzi Agr6 et al., 1972). During the first clays of intoxication a 50% increase of brain rhodanese activity was detected, showing this enzymatic system to be functioning at its maximal rate detoxifying the cyanide in this target tissue• No changes were detected for the heart enzyme measured in the presence of cyanide, but it was slightly modified when no substrate was added to the incubation system. Although labile sulfur concentration was significantly diminished, the system still retained the control activity levels in this vital organ• The high labile sulfur values found in blood correspond with the formation of the very active sulfur substituted form of the enzyme and therefore we would not expect its activity to be modified by the excess of cyanide detected in this tissue• This is the form of rhodanese which would actually detoxify the cyanide. In conclusion, one of the earliest effects of cyanide seems to be an inhibition of the hepatic rhodanese which is presumably due to either blockage by excess binding to the active site and/or depletion of the sulfane-sulfur pool. These changes do not seem to occur in blood where rhodanese functions at its maximal rate, thus preventing cyanide reaching the target tissues and therefore exerting its lethal action• Acknowledgements--A. M. del C. BatUe holds the post of Scientific Research in the Argentine National Research Council (CONICET); E. Vfizquez and A. M. Buzaleh are research fellows at the CONICET. This work was supported by grants from the CONICET, the SECYT, SecretafiA de Salud Pfblica del Ministerio de Bienestar Social, UBA and Banco de la N~ci6n Argentina. We wish to express our gratitude to Lic. S. Afonso for the excellent drawings, and to Laboratios Promeco, B. Aires for providing the animals. 
593 |a Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Facultad de Ciencias Exactas y Naturales, 1448 Buenos Aires, Argentina 
690 1 0 |a CYANIDE 
690 1 0 |a CYTOCHROME C OXIDASE 
690 1 0 |a THIOCYANATE 
690 1 0 |a THIOSULFATE SULFURTRANSFERASE 
690 1 0 |a ANIMAL CELL 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANIMAL MODEL 
690 1 0 |a BLOOD 
690 1 0 |a BRAIN 
690 1 0 |a DETOXIFICATION 
690 1 0 |a HEART 
690 1 0 |a INTOXICATION 
690 1 0 |a LIVER 
690 1 0 |a MOUSE 
690 1 0 |a NONHUMAN 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a ADMINISTRATION, ORAL 
690 1 0 |a ANIMAL 
690 1 0 |a CYANIDES 
690 1 0 |a CYTOCHROME-C OXIDASE 
690 1 0 |a MICE 
690 1 0 |a PROTEINS 
690 1 0 |a SULFUR 
690 1 0 |a SUPPORT, NON-U.S. GOV'T 
690 1 0 |a THIOCYANATES 
690 1 0 |a THIOSULFATE SULFURTRANSFERASE 
690 1 0 |a TIME FACTORS 
700 1 |a Vazquez, E.S. 
700 1 |a Del Battle, C.A.M. 
773 0 |d 1989  |g v. 20  |h pp. 323-327  |k n. 3  |p Gen. Pharmacol. Vasc. Syst.  |x 03063623  |w (AR-BaUEN)CENRE-4808  |t General Pharmacology 
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