EXPEHIMENTAL PARASITOLOGY 48, 126-134 (1979) Trypanosoma brucei: Trypanocidal Effect of Salicylhydroxamic Acid plus Glycerol in Infected Rats C. VAN DER MEER, J. A. M. VERSLUIJS-BROERS Pharmacological Laboratory, University of Amsterdam, Polderweg 104, Amsterdam, The Netherlands AND F. R. OPPERDOES 1 Section for Medical Enzymology and Molecular Biology, Laboratory of Biochemistry, University of Amsterdam, Eerste Constantijn Huygensstraat 20, Amsterdam, The Netherlands (Accepted for Publication 9 March 1979) VAN DER MEER, C., VERSLUIJS-BROERS, J. A. M., AND OPPERDOES, F. R. 1979. Trypano- soma brucei: Trypanocidal effect of salicylhydroxamic acid plus glycerol in infected rats. Experimental Parasitology 48, 126-134. Rats inoculated with Trypanosoma brucei brucei EATRO 427 and having a high degree of parasitemia were treated with a series of intra- peritoneal injections of salicylhydroxamic acid (SHAM) plus glycerol. Permanent cures were obtained with 380 mg/kg SHAM plus 3.8 g/kg glycerol, a dosage regime which was just sublethal. Using a regime with which permanent cure was obtained, the SHAM con- centration in the blood plasma remained above 2 mmole/liter for about 20 min, while the glycerol concentration remained above 22 mmole/liter for about 1 hr. The brain concentra- tion of SHAM was close to the plasma concentration. The concentration of glycerol in the brain remained far below the plasma concentration, reaching 6 to 8 mmole/liter between 1 and 2 hr after the beginning of treatment. Treatment with glycerol did not affect the mobility of the trypanosomes nor the survival of infected rats after treatment with suramin. INDEX DESCRIPTORS: Protozoa, parasitic; Hemoflagellate; Trypanosoma ( Trypanozoon j brucei brucei; Trypanocides; Salicylhydroxamic acid ( SHAM ) ; Glycerol; Suramin; Rat. The bloodstream forms of African try- panosomes use for their aerobic energy production an L-glycerol-Sphosphate oxi- dase system. Inhibitors of this oxidase were expected to be specific and effective agents directed against these bloodstream forms. However, in a previous paper (Opperdoes et al. 1976) it was shown that salicyl- hydroxamic acid (SHAM), in doses result- 1 Present address: International Institute of Cellular and Molecular Pathology, Tropical Re- search Unit Avenue Hippocrate 74, B-1200 Brussels, Belgium. ing in plasma concentrations expected to inhibit the L-glycerol-3-phosphate oxidase by more than 9Q%, was unable to cure rats infected with Trypanosoma brucei brucei. Clarkson and Brohn (1976) and Fair- Iamb et al. (1977) found that T. brucei brucei incubated in vitro with a combina- tion of SHAM and glycerol, rapidly and completely lost its mobility and that pyru- vate production, and therefore glycolysis, was completely blocked under these con- ditions. These experiments suggested that treatment with this combination might be effective, against the bloodstream forms. 126 0014-4&94/79/040126-09$02.00/0 Copyright @ 1979 by Academic Press, Inc. All rights of reproduction in any form reserved.