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Toxicity of Halogenated Oxyquinolines in Dogs. A Clinical Study

III. Intoxication Experiments

Acta Veterinaria Scandinavica volume 15, pages 398–418 (1974)Cite this article

Abstract

LANNEK, BIRGITTA and PAUL LINDBERG: Toxicity of halogenated oxyquinolines in dogs. A clinical study. III. Intoxication experiments. Acta vet. scand. 1974, 15, 398–418. — Oxyquinoline drugs, which are normally well tolerated by dogs, will cause disease when a dog’s resistance is occasionally lowered. In a series of experiments in dogs we tried to reproduce the disease pattern of spontaneous cases of poisoning. Most of these experiments, using even high single or repeated oral doses, failed. It was observed, more or less by chance, that the intestinal absorption of 125I-labelled vioform was greatly increased when the dog was not fasted. The consumption of fat, but not of protein or carbohydrates, was found to be the responsible factor. When the oxyquinoline drug was given in a fat emulsion, approx. 1/3 of the dogs fell ill. When fouled fish was also added, the dose necessary to produce disease was lowered to the range used in vioform therapy. We believe that phenolic substances, which may be produced from bacterial degradation of proteins in intestinal disorders, compete with oxyquinolines in metabolic and elimination processes.

vioform; oxyquinolines; dogs; convulsions; heart injury; liver injury; poisoning; diarrhoea; phenolic substances.

Sammanfattning

Toxiciteten av halogenerade oxikinoliner hos hund. En klinisk studie. III. Intoxikationsförsök.

Oxikinolinpreparat, vilka normalt tolereras väl av hundar, kan framkalla sjukdom när hundens resistens tillfälligt är minskad. Författarna har försökt framkalla sjukdomsmönstret vid spontan oxikinolinförgiftning i en försöksserie på hundar. Flertalet av dessa försök, även med enstaka eller upprepade höga doser givna per os, misslyckades. Av en tillfällighet observerades, att absorptionen från tarmen av 125J-märkt vioform ökade, när hundarna hade ätit strax före givan. Intagandet av fett, men ej protein eller kolhydrat, visade sig vara den ansvariga faktorn. När oxikinolin gavs i en fettemulsion, insjuknade ungefär 1/3 av hundarna. Tillsattes rutten strömming, kunde den sjukdomsframkallande dosen sänkas till samma nivå som vid spontan vioformförgiftning. Författarna anser, att substanser av fenolkaraktär, vilka bildas genom nedbrytning av proteiner vid tarmåkommor, „tävlar“ med oxikinolinerna vid nedbrytning och elimination.

References

  • Albert, A.: Selective Toxicity. 4th Ed., Methuen & Go. Ltd., London 1968.

  • Albert, A., S. D. Rubbo, R. J. Goldacre & B. G. Balfour: The influence of chemical constitution on antibacterial activit. Part III: A study of 8-hydroxyquinoline (oxine) and related compounds. Brit. J. exp. Path. 1947, 28, 69–87.

    CAS  Google Scholar 

  • Berggren, L. & O. Hansson: Absorption of intestinal antiseptics derived from 8-hydroxyquinolines. Clin. Pharmacol. Ther. 1968, 9, 67–70.

    Article  CAS  Google Scholar 

  • Candlin, F. T.: The liver. In Canine Medicine. 1st Catcott Ed., Amer. vet. Publ., Inc., California 1968.

  • Cantarow, A. & B. Schepartz: Biochemistry. 4th Ed., W. B. Saunders Co., Philadelphia & London 1967.

  • Cohn, H. D. & J. S. Harun: Letter to the Editor. J. Amer. med. Ass. 1972, 220, 276.

    Article  Google Scholar 

  • David, N. A., N. M. Phatak & F. B. Zener: Iodochlorhydroxyquinoline and diiodohydroxyquinoline : animal toxicity and absorption in man. Amer. J. trop. Med. 1944, 24, 29–33.

    Article  Google Scholar 

  • Garner, R. J.: Veterinary Toxicology. 2nd Ed., Baillière, Tindall and Cox, London 1961.

  • Goodman, L. S. & A. Gilman: The Pharmacological Basis of Therapeutics. 4th Ed., The Macmillan Company, New York 1971.

  • Griffith, R. W.: Intestopan, a 26-week oral toxicity study in dogs. Sandoz Ltd., Dept. Pharm. Tox., March 28, 1969 (unpublished).

  • Hangartner, P.: Troubles nerveux observés chez le chien après absorption d’Entéro-Vioforme Ciba. (Nervous symptoms observed in dogs after absorption of Enterovioform Ciba). Schweiz. Arch. Tierheilk. 1965, 107, 43–47.

    Google Scholar 

  • Haskins, W. T., G. W. Luttermoser & F. J. Brady: The physiological disposition of diodoquin, vioform and chiniofon in the rabbit as determined with radioiodine. Amer. J. trop. Med. 1950, 30, 599–612.

    Article  CAS  Google Scholar 

  • Haskins, W. T. & G. W. Luttermoser: Urinary excretion of vioform and diodoquin in rabbits. J. Pharmacol. exp. Ther. 1953, 109, 201–205.

    CAS  PubMed  Google Scholar 

  • Knight, A. A. & J. Miller: Comparative studies on the iodine absorption of Anayodin, Chiniofon, Diodoquin, and Vioform in man. Ann. intern. Med. 1949, 30, 1180–1187.

    Article  CAS  Google Scholar 

  • Lannek, B.: Leverbiopsi hos hund. Ett diagnostiskt hjälpmedel. (Liver biopsy in dogs. A diagnostic aid). Svensk Vet.-Tidn. 1968, 21, 591–594.

    Google Scholar 

  • Lannek, B.: Toxicity of halogenated oxyquinolines in dogs. A clinical study. I. A survey of cases. Acta vet. scand. 1973, 14, 723–744.

    CAS  PubMed  Google Scholar 

  • Lannek, B.: Toxicity of halogenated oxyquinolines in dogs. A clinical study. II. History, symptoms, laboratory findings, therapy, and follow-up. Acta vet. scand. 1974, 15, 219–238.

    CAS  PubMed  Google Scholar 

  • Lannek, B. & L. Jönsson: Toxicity of halogenated oxyquinolines in dogs. A clinical study. V. Pathological findings. Acta vet. scand. 1974, 15. In press.

  • Lannek, B. & P. Lindberg: Vioform poisoning in dogs. The absorption of vioform from the intestine. Svensk Vet.-Tidn. 1972 a, 11, 438–441.

    Google Scholar 

  • Lannek, B. & P. Lindberg: Toxicity of halogenated oxyquinolines to dogs. The effect of feeding fouled herring. Acta vet. scand. 1972 b, 13, 441–442.

    Article  CAS  Google Scholar 

  • Lannek, B. & P. Lindberg: Toxicity of halogenated oxyquinolines in dogs. A clinical study. IV. Tissue distribution and elimination in urine. Acta vet. scand. 1974, 15, 419–435.

    CAS  PubMed  Google Scholar 

  • Mentzing, L. O. & O. Ringertz: Salmonella infection in tourists. 2. Prophylaxis against Salmonellosis. Acta path. microbiol. scand. 1968, 74, 405–413.

    Article  CAS  Google Scholar 

  • Millier, L. F.: Die Mexaformvergiftung des Hundes (Klinische Demonstration). (The mexaform poisoning in the dog. Clinical demonstration). Kleintier-Prax. 1967, 12, 51–52.

    Google Scholar 

  • Palm, A.: Untersuchungen in der Chinolinreihe. X. Mitteilung: Dijodverbindungen. (Investigations of the quinoline derivatives. X. Communication: Diiodo compounds). Naunyn-Schmiedeberg’s Arch. exp. Path. Pharmak. 1932, 166, 176–185.

    Google Scholar 

  • Püschner, H. & R. Fankhauser: Neuropathologische Befunde bei experimenteller Vioform-Vergiftung der weissen Maus. (Neurological symptoms after experimental Vioform poisoning in the white mouse). Schweiz. Arch. Tierheilk. 1969, 111, 371–379.

    Google Scholar 

  • Reichard, H.: Ornithine Carbamyl Transferase in dog serum on intravenous injection of enzyme, choledochus ligation, and carbontetrachloride poisoning. J. Lab. clin. Med. 1959, 53, 417–425.

    CAS  PubMed  Google Scholar 

  • Ritter, P. & M. Jermann: Vergleichende Untersuchungen über Resorption und Stoffwechsel einiger therapeutisch angewendeter 8-Hydroxychinolin. (Comparative study on the absorption and the metabolism of some 8-hydroxyquinolines for therapeutic use). Arzneimittel-Forsch. 1966, 16, 1647–1652.

    CAS  Google Scholar 

  • Sigma Technical Bulletin No. 505. The colorimetric determination of glutamic-oxalacetic and glutamic-pyruvic transaminases. 1967.

  • Schantz, B. & B. Wikström: Suspected poisoning with oxyquinoline preparations in dogs. Svensk Vet.-Tidn. 1965, 4, 106–107.

    Google Scholar 

  • Tateishi, J., S. Kuroda, A. Saito & S. Otsuki: Myelo-optic neuropathy induced by clioquinol in animals. Lancet 1971, 2, 1263–1264.

    Article  CAS  Google Scholar 

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  1. Department of Medicine I, Royal Veterinary College, Stockholm 50, Stockholm, S-104 05, Sweden

    Birgitta Lannek & Paul Lindberg

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  1. Birgitta Lannek
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  2. Paul Lindberg
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Supported by grants from the Swedish Medical Research Gouncil.

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Lannek, B., Lindberg, P. Toxicity of Halogenated Oxyquinolines in Dogs. A Clinical Study. Acta Vet Scand 15, 398–418 (1974). https://doi.org/10.1186/BF03547467

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Acta Veterinaria Scandinavica

ISSN: 1751-0147