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. 1992 Aug;36(8):1630–1634. doi: 10.1128/aac.36.8.1630

Hexadecylphosphocholine: oral treatment of visceral leishmaniasis in mice.

A Kuhlencord 1, T Maniera 1, H Eibl 1, C Unger 1
PMCID: PMC192021  PMID: 1329624

Abstract

Hexadecylphosphocholine (He-PC), a novel phospholipid derivative, was tested against Leishmania donovani and Leishmania infantum, the causative agents of visceral leishmaniasis. In vitro, promastigotes were highly susceptible to He-PC; the 50% inhibitory concentrations were between 0.89 and 2.25 micrograms/ml for the different leishmanial strains. In vivo, a marked antileishmanial activity in infected BALB/c mice could be demonstrated after oral administration of He-PC. Whereas parasite suppression and killing in the liver were comparable after 5 days of treatment with He-PC (10 or 20 mg/kg of body weight per day administered orally) and sodium stibogluconate (120 mg of pentavalent antimonal agent per kg/day administered subcutaneously), a superior reduction in the parasite load in the spleen and bone marrow was observed after oral treatment with He-PC. After a 4-week treatment period, parasite suppression in the spleen was better than that observed with standard sodium stibogluconate therapy by a factor of more than 600.

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Selected References

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  1. Baumann R. J., McCann P. P., Bitonti A. J. Suppression of Leishmania donovani by oral administration of a bis(benzyl)polyamine analog. Antimicrob Agents Chemother. 1991 Jul;35(7):1403–1407. doi: 10.1128/aac.35.7.1403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berens R. L., Marr J. J. An easily prepared defined medium for cultivation of Leishmania donovani promastigotes. J Parasitol. 1978 Feb;64(1):160–160. [PubMed] [Google Scholar]
  3. Berman J. D. Chemotherapy for leishmaniasis: biochemical mechanisms, clinical efficacy, and future strategies. Rev Infect Dis. 1988 May-Jun;10(3):560–586. doi: 10.1093/clinids/10.3.560. [DOI] [PubMed] [Google Scholar]
  4. Berman J. D., Wyler D. J. An in vitro model for investigation of chemotherapeutic agents in leishmaniasis. J Infect Dis. 1980 Jul;142(1):83–86. doi: 10.1093/infdis/142.1.83. [DOI] [PubMed] [Google Scholar]
  5. Breiser A., Kim D. J., Fleer E. A., Damenz W., Drube A., Berger M., Nagel G. A., Eibl H., Unger C. Distribution and metabolism of hexadecylphosphocholine in mice. Lipids. 1987 Nov;22(11):925–926. doi: 10.1007/BF02535556. [DOI] [PubMed] [Google Scholar]
  6. Carter K. C., Baillie A. J., Alexander J., Dolan T. F. The therapeutic effect of sodium stibogluconate in BALB/c mice infected with Leishmania donovani is organ-dependent. J Pharm Pharmacol. 1988 May;40(5):370–373. doi: 10.1111/j.2042-7158.1988.tb05271.x. [DOI] [PubMed] [Google Scholar]
  7. Chunge C. N., Gachihi G., Muigai R., Wasunna K., Rashid J. R., Chulay J. D., Anabwani G., Oster C. N., Bryceson A. D. Visceral leishmaniasis unresponsive to antimonial drugs. III. Successful treatment using a combination of sodium stibogluconate plus allopurinol. Trans R Soc Trop Med Hyg. 1985;79(5):715–718. doi: 10.1016/0035-9203(85)90200-7. [DOI] [PubMed] [Google Scholar]
  8. Croft S. L., Neal R. A., Pendergast W., Chan J. H. The activity of alkyl phosphorylcholines and related derivatives against Leishmania donovani. Biochem Pharmacol. 1987 Aug 15;36(16):2633–2636. doi: 10.1016/0006-2952(87)90543-0. [DOI] [PubMed] [Google Scholar]
  9. Eibl H., Unger C. Hexadecylphosphocholine: a new and selective antitumor drug. Cancer Treat Rev. 1990 Sep;17(2-3):233–242. doi: 10.1016/0305-7372(90)90053-i. [DOI] [PubMed] [Google Scholar]
  10. Haase R., Wieder T., Geilen C. C., Reutter W. The phospholipid analogue hexadecylphosphocholine inhibits phosphatidylcholine biosynthesis in Madin-Darby canine kidney cells. FEBS Lett. 1991 Aug 19;288(1-2):129–132. doi: 10.1016/0014-5793(91)81018-4. [DOI] [PubMed] [Google Scholar]
  11. Heinzel F. P., Sadick M. D., Holaday B. J., Coffman R. L., Locksley R. M. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med. 1989 Jan 1;169(1):59–72. doi: 10.1084/jem.169.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hilgard P., Stekar J., Voegeli R., Engel J., Schumacher W., Eibl H., Unger C., Berger M. R. Characterization of the antitumor activity of hexadecylphosphocholine (D 18506). Eur J Cancer Clin Oncol. 1988 Sep;24(9):1457–1461. doi: 10.1016/0277-5379(88)90336-7. [DOI] [PubMed] [Google Scholar]
  13. Hochhuth C. H., Vehmeyer K., Eibl H., Unger C. Hexadecylphosphocholine induces interferon-gamma secretion and expression of GM-CSF mRNA in human mononuclear cells. Cell Immunol. 1992 Apr 15;141(1):161–168. doi: 10.1016/0008-8749(92)90135-c. [DOI] [PubMed] [Google Scholar]
  14. Hochhuth C., Berkovic D., Eibl H., Unger C., Doenecke D. Effects of antineoplastic phospholipids on parameters of cell differentiation in U937 cells. J Cancer Res Clin Oncol. 1990;116(5):459–466. doi: 10.1007/BF01612994. [DOI] [PubMed] [Google Scholar]
  15. Jha T. K. Evaluation of allopurinol in the treatment of kala-azar occurring in North Bihar, India. Trans R Soc Trop Med Hyg. 1983;77(2):204–207. doi: 10.1016/0035-9203(83)90071-8. [DOI] [PubMed] [Google Scholar]
  16. Peters B. S., Fish D., Golden R., Evans D. A., Bryceson A. D., Pinching A. J. Visceral leishmaniasis in HIV infection and AIDS: clinical features and response to therapy. Q J Med. 1990 Nov;77(283):1101–1111. doi: 10.1093/qjmed/77.2.1101. [DOI] [PubMed] [Google Scholar]
  17. Peters W., Trotter E. R., Robinson B. L. The experimental chemotherapy of leishmaniasis, V. The activity of potential leishmanicides against 'L. infantum LV9' in NMRI mice. Ann Trop Med Parasitol. 1980 Jun;74(3):289–297. [PubMed] [Google Scholar]
  18. Peters W., Trotter E. R., Robinson B. L. The experimental chemotherapy of leishmaniasis, VII. Drug responses of L. major and L. mexicana amazonensis, with an analysis of promising chemical leads to new antileishmanial agents. Ann Trop Med Parasitol. 1980 Jun;74(3):321–335. [PubMed] [Google Scholar]
  19. Saenz R. E., Paz H. M., Johnson C. M., Marr J. J., Nelson D. J., Pattishall K. H., Rogers M. D. Treatment of American cutaneous leishmaniasis with orally administered allopurinol riboside. J Infect Dis. 1989 Jul;160(1):153–158. doi: 10.1093/infdis/160.1.153. [DOI] [PubMed] [Google Scholar]
  20. Saenz R. E., Paz H., Berman J. D. Efficacy of ketoconazole against Leishmania braziliensis panamensis cutaneous leishmaniasis. Am J Med. 1990 Aug;89(2):147–155. doi: 10.1016/0002-9343(90)90292-l. [DOI] [PubMed] [Google Scholar]
  21. Sundar S., Kumar K., Singh V. P. Ketoconazole in visceral leishmaniasis. Lancet. 1990 Dec 22;336(8730):1582–1583. doi: 10.1016/0140-6736(90)93358-v. [DOI] [PubMed] [Google Scholar]
  22. Sypek J. P., Wyler D. J. Antileishmanial defense in macrophages triggered by tumor necrosis factor expressed on CD4+ T lymphocyte plasma membrane. J Exp Med. 1991 Oct 1;174(4):755–759. doi: 10.1084/jem.174.4.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Unger C., Damenz W., Fleer E. A., Kim D. J., Breiser A., Hilgard P., Engel J., Nagel G., Eibl H. Hexadecylphosphocholine, a new ether lipid analogue. Studies on the antineoplastic activity in vitro and in vivo. Acta Oncol. 1989;28(2):213–217. doi: 10.3109/02841868909111249. [DOI] [PubMed] [Google Scholar]
  24. Unger C., Fleer E., Damenz W., Hilgard P., Nagel G., Eibl H. Hexadecylphosphocholine: determination of serum concentrations in rats. J Lipid Mediat. 1991 Jan-Feb;3(1):71–78. [PubMed] [Google Scholar]
  25. Vehmeyer K., Eibl H., Unger C. Hexadecylphosphocholine stimulates the colony-stimulating factor-dependent growth of hemopoietic progenitor cells. Exp Hematol. 1992 Jan;20(1):1–5. [PubMed] [Google Scholar]
  26. Vehmeyer K., Scheurich P., Eibl H., Unger C. Hexadecylphosphocholine-mediated enhancement of T-cell responses to interleukin 2. Cell Immunol. 1991 Oct 1;137(1):232–238. doi: 10.1016/0008-8749(91)90072-j. [DOI] [PubMed] [Google Scholar]

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