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Antimicrobial Agents and Chemotherapy, September 2000, p. 2406-2410, Vol. 44, No. 9
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Sodium Stibogluconate (Pentostam) Potentiates Oxidant Production in Murine Visceral Leishmaniasis and in Human Blood

Samira Rais,1,2 Axel Perianin,3 Monique Lenoir,3 Abderrahim Sadak,4 Daniele Rivollet,1 Muriel Paul,5 and Michele Deniau1,*

Service de Parasitologie, Faculté de Médecine,1 and Service de Pharmacie,5 CHU Henri Mondor, 94010 Créteil, and CNRS UPRES-A 8068, Pharmacologie, Hôpital Cochin, 75014 Paris,3 France, and Laboratoire de Parasitologie, Faculté des Sciences, Rabat,4 and Laboratoire de Biochimie, Faculté des Sciences Ben M'sik, Casablanca,2 Morocco

Received 7 February 2000/Returned for modification 5 April 2000/Accepted 7 June 2000

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 µg/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.

* Corresponding author. Mailing address: Laboratoire de Parasitologie, Faculté de Médecine de Créteil, 8, rue du Général Sarrail, 94010 Créteil, France. Phone: (33) 1 49 81 36 31. Fax: (33) 1 49 81 36 01. E-mail: deniau{at}univ-paris12.fr.

Antimicrobial Agents and Chemotherapy, September 2000, p. 2406-2410, Vol. 44, No. 9
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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