A direct comparison of sodium stibogluconate treatment in two animal models of human visceral leishmaniasis, mouse and hamster.

K. C. Carter, J. O'Grady, T. F. Dolan, A. J. Baillie, J. Alexander, J. Keys

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The effect of sodium stibogluconate therapy, in the free or liposomal form, on the spleen, liver and bone marrow parasite burdens of L. donovani infected mice (BALB/c and B10) and hamsters was studied. Animals were infected i.v. (tail vein in mice, jugular vein in hamsters) and treated on either days 7 and 8 postinfection (acute model) or on days 31 and 32 postinfection or later (chronic model) with free (44.4 mg Sb (v)/kg/day) or liposomal (7.1 mg Sb (v)/kg/day) drug. Six days after the second drug dose animals were killed and parasite burdens assessed. Comparison of the parasite burdens in untreated L. donovani infected mice (B10 and BALB/c) and hamsters showed that higher burdens were obtained in hamsters in all 3 infection sites when the data were expressed as Leishman-Donovan units. However, if the data were expressed as the number of parasites/1000 host cell nuclei, liver burdens were similar in the two species although the parasite burdens remained higher in the spleen and bone marrow of hamsters. In the acute model, both free and liposomal drug treatment significantly reduced liver and spleen parasite burdens in BALB/c mice compared with controls, the liposomal form being significantly more suppressive at a sixth of the free drug dose. The two treatments had little effect on murine bone marrow burdens. In the hamster, the relative efficacies of the free and liposomal forms of the drug in the liver were similar to that in the mouse but in the spleen and bone marrow both treatments markedly reduced parasite numbers. The parasites in the hamster were therefore much more susceptible to drug treatment and this species-dependent effect was most marked in the bone marrow. In mice suffering from the chronic infection the effectiveness of free and liposomal stibogluconate decreased with the length of infection. A similar effect was also demonstrated in hamsters.
LanguageEnglish
Pages129-137
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume53
Issue number2
DOIs
Publication statusPublished - 15 Jul 1989

Fingerprint

Antimony Sodium Gluconate
Visceral Leishmaniasis
Cricetinae
Parasites
Animal Models
Bone Marrow
Spleen
Pharmaceutical Preparations
Liver
Infection
Jugular Veins
Cell Nucleus
Tail
Veins

Keywords

  • Leishmania donovani
  • sodium stibogluconate
  • liposome
  • acute infection
  • chronic infection
  • BALB/c mouse
  • B10 mouse
  • golden syrian hamster

Cite this

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title = "A direct comparison of sodium stibogluconate treatment in two animal models of human visceral leishmaniasis, mouse and hamster.",
abstract = "The effect of sodium stibogluconate therapy, in the free or liposomal form, on the spleen, liver and bone marrow parasite burdens of L. donovani infected mice (BALB/c and B10) and hamsters was studied. Animals were infected i.v. (tail vein in mice, jugular vein in hamsters) and treated on either days 7 and 8 postinfection (acute model) or on days 31 and 32 postinfection or later (chronic model) with free (44.4 mg Sb (v)/kg/day) or liposomal (7.1 mg Sb (v)/kg/day) drug. Six days after the second drug dose animals were killed and parasite burdens assessed. Comparison of the parasite burdens in untreated L. donovani infected mice (B10 and BALB/c) and hamsters showed that higher burdens were obtained in hamsters in all 3 infection sites when the data were expressed as Leishman-Donovan units. However, if the data were expressed as the number of parasites/1000 host cell nuclei, liver burdens were similar in the two species although the parasite burdens remained higher in the spleen and bone marrow of hamsters. In the acute model, both free and liposomal drug treatment significantly reduced liver and spleen parasite burdens in BALB/c mice compared with controls, the liposomal form being significantly more suppressive at a sixth of the free drug dose. The two treatments had little effect on murine bone marrow burdens. In the hamster, the relative efficacies of the free and liposomal forms of the drug in the liver were similar to that in the mouse but in the spleen and bone marrow both treatments markedly reduced parasite numbers. The parasites in the hamster were therefore much more susceptible to drug treatment and this species-dependent effect was most marked in the bone marrow. In mice suffering from the chronic infection the effectiveness of free and liposomal stibogluconate decreased with the length of infection. A similar effect was also demonstrated in hamsters.",
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A direct comparison of sodium stibogluconate treatment in two animal models of human visceral leishmaniasis, mouse and hamster. / Carter, K. C.; O'Grady, J.; Dolan, T. F. ; Baillie, A. J.; Alexander, J.; Keys, J.

In: International Journal of Pharmaceutics, Vol. 53, No. 2, 15.07.1989, p. 129-137.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A direct comparison of sodium stibogluconate treatment in two animal models of human visceral leishmaniasis, mouse and hamster.

AU - Carter, K. C.

AU - O'Grady, J.

AU - Dolan, T. F.

AU - Baillie, A. J.

AU - Alexander, J.

AU - Keys, J.

PY - 1989/7/15

Y1 - 1989/7/15

N2 - The effect of sodium stibogluconate therapy, in the free or liposomal form, on the spleen, liver and bone marrow parasite burdens of L. donovani infected mice (BALB/c and B10) and hamsters was studied. Animals were infected i.v. (tail vein in mice, jugular vein in hamsters) and treated on either days 7 and 8 postinfection (acute model) or on days 31 and 32 postinfection or later (chronic model) with free (44.4 mg Sb (v)/kg/day) or liposomal (7.1 mg Sb (v)/kg/day) drug. Six days after the second drug dose animals were killed and parasite burdens assessed. Comparison of the parasite burdens in untreated L. donovani infected mice (B10 and BALB/c) and hamsters showed that higher burdens were obtained in hamsters in all 3 infection sites when the data were expressed as Leishman-Donovan units. However, if the data were expressed as the number of parasites/1000 host cell nuclei, liver burdens were similar in the two species although the parasite burdens remained higher in the spleen and bone marrow of hamsters. In the acute model, both free and liposomal drug treatment significantly reduced liver and spleen parasite burdens in BALB/c mice compared with controls, the liposomal form being significantly more suppressive at a sixth of the free drug dose. The two treatments had little effect on murine bone marrow burdens. In the hamster, the relative efficacies of the free and liposomal forms of the drug in the liver were similar to that in the mouse but in the spleen and bone marrow both treatments markedly reduced parasite numbers. The parasites in the hamster were therefore much more susceptible to drug treatment and this species-dependent effect was most marked in the bone marrow. In mice suffering from the chronic infection the effectiveness of free and liposomal stibogluconate decreased with the length of infection. A similar effect was also demonstrated in hamsters.

AB - The effect of sodium stibogluconate therapy, in the free or liposomal form, on the spleen, liver and bone marrow parasite burdens of L. donovani infected mice (BALB/c and B10) and hamsters was studied. Animals were infected i.v. (tail vein in mice, jugular vein in hamsters) and treated on either days 7 and 8 postinfection (acute model) or on days 31 and 32 postinfection or later (chronic model) with free (44.4 mg Sb (v)/kg/day) or liposomal (7.1 mg Sb (v)/kg/day) drug. Six days after the second drug dose animals were killed and parasite burdens assessed. Comparison of the parasite burdens in untreated L. donovani infected mice (B10 and BALB/c) and hamsters showed that higher burdens were obtained in hamsters in all 3 infection sites when the data were expressed as Leishman-Donovan units. However, if the data were expressed as the number of parasites/1000 host cell nuclei, liver burdens were similar in the two species although the parasite burdens remained higher in the spleen and bone marrow of hamsters. In the acute model, both free and liposomal drug treatment significantly reduced liver and spleen parasite burdens in BALB/c mice compared with controls, the liposomal form being significantly more suppressive at a sixth of the free drug dose. The two treatments had little effect on murine bone marrow burdens. In the hamster, the relative efficacies of the free and liposomal forms of the drug in the liver were similar to that in the mouse but in the spleen and bone marrow both treatments markedly reduced parasite numbers. The parasites in the hamster were therefore much more susceptible to drug treatment and this species-dependent effect was most marked in the bone marrow. In mice suffering from the chronic infection the effectiveness of free and liposomal stibogluconate decreased with the length of infection. A similar effect was also demonstrated in hamsters.

KW - Leishmania donovani

KW - sodium stibogluconate

KW - liposome

KW - acute infection

KW - chronic infection

KW - BALB/c mouse

KW - B10 mouse

KW - golden syrian hamster

U2 - 10.1016/0378-5173(89)90236-6

DO - 10.1016/0378-5173(89)90236-6

M3 - Article

VL - 53

SP - 129

EP - 137

JO - International Journal of Pharmaceutics

T2 - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 2

ER -