Skip to main content
Download PDF
  • Published:

Toxicity of Halogenated Oxyquinolines in Dogs. a Clinical Study

Toxiciteten av halogenerade oxikinoliner hos hund. En klinisk Studie. V. Patolog-anatomiska förändringar

V. Pathological Findings

Acta Veterinaria Scandinavica volume 15, pages 461–486 (1974)Cite this article

Abstract

A description is given of the post-mortem findings in 21 cases of acute spontaneous oxyquinoline poisoning in dogs after administration of halogenated oxyquinoline drugs once or over a short period. The findings are in accordance with the results of necropsy of 7 cases of experimentally induced oxyquinoline poisoning. Biopsy specimens of the liver were taken in 18 dogs. The investigation reveals that spontaneous as well as experimental poisonings give rise to severe myocardial and liver injuries. The myocardial lesions consisted of focal necrosis with interstitial cellular reaction. The areas of necrosis were most frequent in the papillary muscles of the left ventricle. The liver-cell damage ranged from cloudy swelling to hydropic degeneration with depositions of lipids. In 3 experimental cases, in which rapid fixation methods were used, it was possible to evaluate the pathological lesions in the neurons of the brain and spinal cord. Degenerative neuronal changes with chromatolysis and vacuolation were observed, especially in the hippocampus and hypothalamus. It was presumed that the injuries and destruction of these structures had caused symptoms that were consistent with the clinical pictures of the dogs. The clinical symptoms and post-mortem changes were believed to be due to a toxic effect on the myocardium, liver, and central nervous system.

Sammanfattning

Författarna beskriver postmortala fynd hos 21 fall av akut spontan oxikinolinförgiftning hos hund efter behandling med läkemedel innehållande halogenerade oxikinolinderivat en gång eller under kort tid. Fynden överensstämmer med obduktionerna av 7 fall av experimentell oxikinolinförgiftning. Leverbiopsier har tagits i 18 fall. Föreliggande undersökning visar att en svår myokard- och leverskada utvecklas i såväl spontana som experimentella fall. Myokardskadorna bestod av fokala nekroser med cellreaktion i interstitiet. Nekroserna var vanligast förekommande i vänster kammares papillarmuskler. Levercellskadan varierade från albuminös degeneration till hydropisk degeneration med förfettning. I 3 experimentella fall, vilka snabbfixerades, förelåg patologiska förändringar i hjärnan och ryggmärgens neuroner. Degenerativa nervförändringar med kromatolys och vakuolisering sågs främst i hippocampus och hypothalamus. Skador i dessa strukturer kan förmodas ge upphov till symptom, vilka överensstämmer med hundarnas kliniska bild. Symptombilden och de postmortala fynden antas bero på en direkt toxisk effekt på myokardiet, levern och centrala nervsystemet.

References

  • Annotation: More on S.M.O.N Lancet 1971, 2, 1244.

  • Bajusz, E. & G. Jasmin: Enzyme histochemistry of some chemically induced cardiac necroses. I. Myocardial lesions induced by plasmocid. II. Vitamin-, Hormon- und Fermentforsch. 1965, 14, 28–42.

    CAS  Google Scholar 

  • Bajusz, E., G. Jasmin & A. Mongeau: Dissociation by forced muscular exercise of the cardiotoxic from the myotoxic actions of plasmocid. Rev. canad. Biol. 1964, 23, 29–36.

    CAS  PubMed  Google Scholar 

  • Bengtsson, K. & O. Vikrot: Retrograd amnesi efter broxikinolin. (Retrograde amnesia after broxyquinoline). Svenska Läk.-Tidn. 1972, 69, 14–16.

    Google Scholar 

  • Berggren, L. & O. Hansson: Treating acrodermatitis enteropathica. Lancet 1966, 1, 52.

    Article  Google Scholar 

  • Berggren, L., O. Hansson & I. Wahlberg: Läkemedelsbiverkan och tarm-resorbtion av 8-hydroxikinolinpreparat. (Secondary effect and absorption from the intestine of 8-hydroxyquinoline drugs). Svenska Läk.-Tidn. 1968, 65, 3772–3773.

    Google Scholar 

  • D’Agostino, A. N.: An electron microscopic study of skeletal and cardiac muscle of the rat poisoned by plasmocid. Lab. Invest. 1963, 12, 1060–1071.

    Google Scholar 

  • Drachman, D. A. & J. Arbit: Memory and the hippocampal complex. Arch. Neurol. (Chic.) 1966, 15, 52–61.

    Article  CAS  Google Scholar 

  • Etheridge, J. E., Jr. & G. T. Stewart: Treating acrodermatitis enteropathica. Lancet 1966, 1, 261–262.

    Article  Google Scholar 

  • 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 Giba. (Nervous symptoms observed in dogs after absorption of Enterovioform Ciba). Schweiz. Arch. Tierheilk. 1965, 107, 43–47.

    Google Scholar 

  • Hoerlein, B. F.: Canine Neurology — Diagnosis and Treatment. 2nd Ed., W. B. Saunders Company, Philadelphia 1971.

  • Igata, A.: Comments. Lancet 1971, 2, 42–43.

    Google Scholar 

  • Kaeser, H. E. & G. Scollo-Lavizzari: Akute zerebrale Störungen nach hohen Dosen eines Oxychinolinderivates. (Acute cerebral disturbance after high doses of an oxyquinoline derivative). Dtsch. med. Wschr. 1970, 95, 394–397.

    CAS  Google Scholar 

  • Kaeser, H. E. & R. Wüthrich: Zur Frage der Neurotoxizität der Oxychinoline. (On the possible neurotoxicity of oxyquinoline). Dtsch. med. Wschr. 1970, 95, 1685–1688.

    Article  CAS  Google Scholar 

  • Kjaersgaard, K.: Amnesia after clioquinol. Lancet 1971, 2, 1086.

    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.

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

    Google Scholar 

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

    Article  CAS  Google Scholar 

  • Lannek, B. & P. Lindberg: Toxicity of halogenated oxyquinolines in dogs. A clinical study. III. Intoxication experiments. Acta vet. scand. 1974a, 15, 398–418.

    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 b, 15, 419–435.

    CAS  PubMed  Google Scholar 

  • Marshall, P. N. & R. W. Horobin: The chemical nature of the gallocyanin-chrome alum staining complex. Stain Technol. 1972, 47, 155–161.

    Article  CAS  Google Scholar 

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

    Google Scholar 

  • Nakae, K., S. Yamamoto & A. Igata: Subacute myelo-opticoneuropathy (S.M.O.N.) in Japan. Lancet 1971, 2, 510–512.

    Article  CAS  Google Scholar 

  • Poley, R. W., L. C. D. Fobes & M. J. Hall: Fuchsinophilia in early myocardial infarction. Arch. Path. 1964, 77, 325–329.

    CAS  PubMed  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 

  • Redding, R. W.: Diagnosis and therapy of seizures. J. Animal Hosp. Ass. 1969, 5, 79–92.

    Google Scholar 

  • Richter, R.: The effect of certain quinoline compounds upon the nervous system of monkeys. J. Neuropath, exp. Neurol. 1949, 8, 155–170.

    Article  CAS  Google Scholar 

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

    Google Scholar 

  • Schmidt, I. G. & L. H. Schmidt: Neurotoxicity of the 8-aminoquinolines. II. Reactions of various experimental animals to plasmocid. J. comp. Neurol. 1949, 91, 337–351.

    CAS  Google Scholar 

  • Schmidt, I. G. & L. H. Schmidt: Neurotoxicity of the 8-amino-quinolines. III. The effects of pentaquine, isopentaquine, primaquine and pamaquine on the central nervous system of the rhesus monkey. J. Neuropath, exp. Neurol. 1951, 10, 231–256.

    CAS  Google Scholar 

  • Schneider, H. & H. Coper: Morphologische Befunde am Zentralnerven-system der Ratte nach Vergiftung mit Antimetaboliten den Nicotinamids (6-aminonicotinsaureamid und 3-acetylpyridin) und einem Chinolinderivat (5-nitro-8-hydroxychinolin). (Morphologic findings in the central nervous system of the rat at poisoning by antimetabolites of the nicotine amids and quinoline derivatives). Arch. Psychiat. Nervenkr. 1968, 211, 138–154.

    CAS  Google Scholar 

  • Sobue, I., K. Ando, M. Iida, T. Takayanagi, Y. Yamamura & Y. Matsuoka: Myeloneuropathy with abdominal disorders in Japan. Neurology (Bombay) 1971, 21, 168–173.

    Article  CAS  Google Scholar 

  • Stahl, J.: Studies on the blood ammonia in liver disease. Ann. intern. Med 1963, 58, 1–24.

    Article  CAS  Google Scholar 

  • Stranduik, B. & R. Zetterstrom: Amaurosis after broxyquinoline. Lancet 1968, 1, 922–923.

    Article  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 

  • Tsubaki, T., Y. Honma & M. Hoshi: Neurological syndrome associated with clioquinol. Lancet 1971, 1, 696–697.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Birgitta Lannek & Lennart Jönsson

Authors
  1. Birgitta Lannek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lennart Jönsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by grants from the Swedish Medical Research Council.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lannek, B., Jönsson, L. Toxicity of Halogenated Oxyquinolines in Dogs. a Clinical Study. Acta Vet Scand 15, 461–486 (1974). https://doi.org/10.1186/BF03547220

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1186/BF03547220

Keywords

Acta Veterinaria Scandinavica

ISSN: 1751-0147