Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-28T05:15:56.977Z Has data issue: false hasContentIssue false
  • English
  • Français

Ethidium bromide: pharmacokinetics and efficacy against trypanosme infections in rabbits and calves

Published online by Cambridge University Press:  06 April 2009

R. J. Gilbert  and
B. A. Newton
R. J. Gilbert
Affiliation:
Medical Research Council Biochemical Parasitology Unit, The Molteno Institute, University of Cambridge, Downing Street, Cambridge CB2 3EE
B. A. Newton
Affiliation:
Medical Research Council Biochemical Parasitology Unit, The Molteno Institute, University of Cambridge, Downing Street, Cambridge CB2 3EE
Get access Rights & Permissions [Opens in a new window]

Summary

[14C[ethidium bromide has been used to determine drug levels in tissues and body fluids of rabbits and calves following intramuscular injection. Uninfected and Trypanosoma brucei- or Trypanosoma congolense-infected animals were studied. Blood and tissue fluid levels reached a maximum within 1 h and then fell rapidly; after 96 h 80–90% of the radioactivity injected had been excreted, approximately one third in urine and two thirds in faeces. By 1 h after injection of 1 mg [14C]ethidium/kg into a T. congolense-infected calf, 70–80% of the radioactivity in blood was found to be bound to trypanosomes. Doses of 1 or 10 mg/kg were found not to be curative for T. congolense or T. brucei infections in rabbits; drug treatment resulted in a period of sub-patent parasitaemia which was always followed by a relapse. Examination of the prophylactic action of ethidium in rabbits showed that the drug extended the pre-patent period following trypanosome inoculation but provided no absolute protection. A period of ‘apparent’ prophylaxis observed after drug treatment of infected rabbits has been correlated with the presence of anti-trypanosome IgG in the serum.

Type
Research Article
Information
Parasitology , Volume 85 , Issue 1 , August 1982 , pp. 127 - 148
Copyright
Copyright © Cambridge University Press 1982

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Axen, R., Porath, J. & Ernback, S. (1967). Chemical coupling of peptides and proteins to polysaccharides by means of cyanogen halides. Nature, London 214, 1302–4.CrossRefGoogle ScholarPubMed
Bratton, A. C. & Marshall, E. K. (1939). A new coupling component for sulphonilamide determination. Journal of Biological Chemistry 128, 537–50.CrossRefGoogle Scholar
Browning, C. H., Morgan, G. T., Robb, J. V. M. & Walls, L. P. (1938). The trypanocidal action of certain phenanthridinium compounds. Journal of Pathology and Bacteriology 46, 203–4.CrossRefGoogle Scholar
Calnan, J. S., Ford, P. M., Holt, P. J. L. & Pflug, J. J. (1972). Implanted tissue cages – a study in rabbits. British Journal of Plastic Surgery 25, 164–74.CrossRefGoogle ScholarPubMed
Crawford, L. V. & Waring, M. J. (1967). The supercoiling of Papilloma virus DNA. Journal of General Virology 1, 387–90.CrossRefGoogle ScholarPubMed
Dean, P. M. & Wakelin, L. P. G. (1979). The docking manoeuvre at a drug receptor: a quantum mechanical study of intercalative attack of ethidium and its carboxylated derivative on a DNA fragment. Philosophical Transactions of the Royal Society of London, B 287, 571–606.Google Scholar
Desowitz, R. S. (1957). Suramin complexes II. Prophylactic activity against Trypanosoma vivax in cattle. Annals of Tropical Medicine and Parasitology 51, 457–63.CrossRefGoogle ScholarPubMed
Ellens, H., Van Renswoude, A. J. B. M. & Kroon, A. M. (1978). Tissue distribution of free and complexed ethidium bromide and its possible relation to cardiotoxicity. Journal of Molecular Medicine 3, 247–55.Google Scholar
Ercoli, N. (1978). True and false prophylaxis in experimental trypanosomiasis. Proceedings of the Society for Experimental Biology and Medicine 157, 397–401.CrossRefGoogle ScholarPubMed
Ford, E. J. H., Wilmshurst, E. C. & Karib, A. A. (1953 a). Studies on ethidium bromide I. The treatment of early Trypanosoma vivax infections in cattle. Veterinary Record 65, 589–90.Google Scholar
Ford, E. J. H., Wilmshurst, E. C. & Karib, A. A. (1953 b). Studies on ethidium bromide II. The treatment of early Trypanosoma congolense infections in cattle. Veterinary Record 65, 907–8.Google Scholar
Gilbert, R. J., Curtis, R. J. & Newton, B. A. (1979). The pharmacokinetics of [14C]ethidium bromide in normal and Trypanosoma congolense infected calves. Parasitology 79, ii.Google Scholar
Gilbert, R. J. & Newton, B. A. (1980). Ethidium bromide: host–trypanosome–drug interactions. In Biochemistry of Parasites and Host Parasite Relationships, The Host Invader Interplay (ed. Van den Bossche, H.), pp. 647–50. Amsterdam: Elsevier/North Holland.Google Scholar
Gomori, G. (1955). Preparation of buffers. Methods in Enzymology 1, 143.Google Scholar
Goodwin, L. G., Goss, M. D. & Lock, J. A. (1950). The chemotherapeutic action of phenan- thridine compounds III. Carbidium ethanesulphonate. British Journal of Pharmacology and Chemotherapy 5, 287–305.CrossRefGoogle Scholar
Goodwin, L. G. & Guy, M. W. (1973). Tissue fluid in rabbits infected with Trypanosoma brucei. Parasitology 66, 499–513.CrossRefGoogle Scholar
Goodwin, L. G. & Tierney, E. D. (1977). Trypanocidal activity of blood and tissue fluid from normal and infected rabbits treated with drugs. Parasitology 74, 33–45.CrossRefGoogle ScholarPubMed
Gray, A. R. & Roberts, C. J. (1971). Transmission of drug-resistant trypanosomes. Parasitology 63, 67–89.CrossRefGoogle Scholar
Hawking, F. & Sen, A. B. (1960). The trypanocidal action of homidium, quinapyramine and suramin. British Journal of Pharmacology and Chemotherapy 15, 567–70.CrossRefGoogle ScholarPubMed
Hill, J. (1965), Studies on isometamidium: the effect of isometamidium, homidium and pyrithidium on the infectivity of trypanosomes for mice. British Journal of Pharmacology and Chemotherapy 25, 658–63.CrossRefGoogle ScholarPubMed
Hill, J. & MacFadzean, J. A. (1963). Studies on isometamidium: depots of isometamidium in mice and rats and their importance for prophylaxis against Trypanosoma congolense. Transactions of the Royal Society of Tropical Medicine and Hygiene 57, 476–84.CrossRefGoogle ScholarPubMed
Jennings, F. W., Whitelaw, D. D. & Urquhakt, G. M. (1977). The relationship between duration of infection with Trypanosoma brucei in mice and the efficacy of chemotherapy. Parasitology 75, 143–53.CrossRefGoogle ScholarPubMed
Kandaswamy, T. S. & Henderson, J. F. (1963). The metabolism of ethidium bromide in normal and neoplastic tissues. Cancer Research 23, 250–3.Google Scholar
Lanham, S. M. & Godfrey, D. G. (1970). Isolation of salivarian trypanosomes from man and other mammals using DEAE cellulose. Experimental Parasitology 28, 521–34.CrossRefGoogle ScholarPubMed
Leach, T. M., Karib, A. A., Ford, E. J. H. & Wilmshurst, E. C. (1955). Studies on ethidium bromide VI. The prophylactic properties of the drug. Journal of Comparative Pathology and Therapeutics 65, 130–42.CrossRefGoogle ScholarPubMed
MacGregor, J. T. & Clarkson, T. W. (1971). Metabolism and biliary excretion of phenan-thridinium salts. Biochemical Pharmacology 20, 2833–46.CrossRefGoogle Scholar
MacGregor, J. T. & Clarkson, T. W. (1972). Biliary excretion of phenanthridinium salts. Biochemical Pharmacology 21, 1679–96.CrossRefGoogle ScholarPubMed
MacLennan, K. J. R. & Na'lsa, B. K. (1970). Relapsing Trypanosoma vivax infections in Nigerian Zebu cattle treated with diminazene aceturate. Tropical Animal Health and Production 2, 189–95.CrossRefGoogle Scholar
Nayak, P. K. & Schanker, L. S. (1969). Active transport of tertiary amine compounds into bile. American Journal of Physiology 217 1639–43.CrossRefGoogle ScholarPubMed
Newton, B. A. (1957). The mode of action of phenanthridines: the effect of ethidium bromide on cell division and nucleic acid synthesis. Journal of General Microbiology 17, 718–30.CrossRefGoogle ScholarPubMed
Newton, B. A. (1976). Antiprotozoal drugs as biochemical probes. In Biochemistry of Parasites and Host Parasite Relationships (ed. van den Bossche, H.), pp. 459–76. Amsterdam: Elsevier/North Holland.Google Scholar
Newton, B. A. & Gilbert, R. J. (1979). Preliminary studies on the pharmacokinetics of [14C]ethidium bromide in rabbits. Parasitology 79, i.Google Scholar
Pulleybank, D. E. & Morgan, A. R. (1975). The sense of naturally occurring superhelices and the unwinding angle of intercalated ethidium. Journal of Molecular Biology 91, 1–13.CrossRefGoogle Scholar
Schanker, L. S. (1968). Secretion of organic compounds in bile. In Handbook of Physiology, Section 6, (ed. Code, C. F.) 5, 2433–49. Washington D.C: American Physiological Society.Google Scholar
Schanker, L. S. & Solomon, H. (1963). Active transport of quarternary ammonium compounds into bile. American Journal of Physiology 204, 829–32.CrossRefGoogle Scholar
Soltys, M. A. (1957). Immunity in trypanosomiasis II. Agglutination reaction with African trypanosomes. Parasitology 47, 390–5.CrossRefGoogle ScholarPubMed
Taylor, A. E. R. (1960 a). The absorbtion, distribution and excretion of prothidium in rats, rabbits and cattle. British Journal of Pharmacology and Chemotherapy 15, 235–42.CrossRefGoogle Scholar
Taylor, A. E. R. (1960 b). The absorption of prothidium by Trypanosoma rhodesiense. British Journal of Pharmacology and Chemotherapy 15, 230–4.CrossRefGoogle ScholarPubMed
Unsworth, K. (1954 a). The curative effect of ethidium bromide against Trypanosoma vivax infections of Zebu cattle in West Africa, with observations on the toxicity of the drug. Annals of Tropical Medicine and Parasitology 48, 229–36.CrossRefGoogle ScholarPubMed
Unsworth, K. (1954 b). Further observations on the curative effect of ethidium bromide against Trypanosoma vivax infections of Zebu cattle in West Africa. Annals of Tropical Medicine and Parasitology 48, 237–41.CrossRefGoogle ScholarPubMed
Voller, A., Bartlett, A. & Bidwell, D. E. (1976). Enzyme immunoassays for parasitic diseases. Transactions of the Royal Society of Tropical Medicine and Hygiene 70, 98–106.CrossRefGoogle Scholar
Waring, M. J. (1975). Ethidium and propidium. In Antibiotics III: Mechanism of Action of Antimicrobial and Antitumour Agents (ed. Corcoran, J. W. and Hahn, F. E.), pp. 141–65. Berlin, Heidelberg and New York: Springer Verlag.Google Scholar
Whiteside, E. F. (1962). Interactions between drugs, trypanosomes and cattle in the field. In Drugs, Parasites and Hosts (ed. Goodwin, L. G. and Nimmo-Smith, R. H.), pp. 116–41. London: J. A. Churchill.Google Scholar
Who/Fao (1979). World Health Organization Technical Report, Series 635, p. 86.Google Scholar
Wilde, J. K. H. & Robson, J. (1953). The effect against Trypanosoma congolense in Zebu cattle of 3 new phenanthridine compounds. Veterinary Record 65, 49–51.Google Scholar
Williamson, J. (1957). Suramin complexes I. Prophylactic activity against Trypanosoma congolense in small animals. Annals of Tropical Medicine and Parasitology 51, 440–56.CrossRefGoogle ScholarPubMed
Williamson, J. (1970). Review of chemotherapeutic and chemoprophylactic agents. In The African Trypanosomiases (ed. Mulligan, H. W.), pp. 125–221. London: Allen and Unwin.Google Scholar
Wilson, S. G. & Faibclough, R. (1953). A preliminary note on the treatment of Trypanosoma congolense infections with ethidium bromide in Kenya Colony. Veterinary Record 65, 201–2.Google Scholar