Sodium stibogluconate (Pentostam) potentiates oxidant production in murine visceral leishmaniasis and in human blood.
Sodium stibogluconate (Sbb), a leishmanicidal drug, was studied for its in vivo effect on the formation of reactive oxygen species (ROS), assessed by chemiluminescence (CL) in the whole blood of mice infected with Leishmania infantum. Stimulation of ROS formation induced ex vivo by zymosan particles or the protein kinase C activator phorbol myristate acetate (PMA) was reduced by approximately 25% (P < 0.05) after infection of mice. Treatment of infected mice with Sbb (50 to 400 mg/kg of body weight) enhanced the blood CL induced by zymosan and PMA (47 to 96%, P < 0.01). The drug potentiation effect also occurred in uninfected mice. In vitro treatment of normal human blood with Sbb (1, 10, or 100 microg/ml) for 1 h primed the CL response to PMA (29 to 54%). The priming effect of Sbb was also observed on the production of superoxide by isolated polymorphonuclear leukocytes stimulated either by PMA and zymosan or by the chemoattractants N-formyl-Met-Leu-Phe and platelet-activating factor. These data provide the first evidence of priming of the phagocyte respiratory burst by Sbb. This novel property of Sbb may contribute to the drug's leishmanicidal effect.
Rais
S
S
Service de Parasitologie, Faculté de Médecine, CHU Henri Mondor, Créteil, France.
Perianin
A
A
Lenoir
M
M
Sadak
A
A
Rivollet
D
D
Paul
M
M
Deniau
M
M
D000818:Animals; D000967:Antimony Sodium Gluconate / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016877:Oxidants / Q000096:biosynthesis; D010586:Phagocytes / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst
D000981:Antiprotozoal Agents; D016877:Oxidants; D017382:Reactive Oxygen Species; D000967:Antimony Sodium Gluconate