didanosine and Toxoplasmosis--Animal

The activities of purine salvage enzymes in tachyzoites from a cyst-forming strain of Toxoplasma gondii were determined using HPLC. Six enzymes were assayed both in vitro and in vivo: adenosine deaminase, guanine deaminase, purine nucleoside phosphorylase, xanthine oxidase, hypoxanthine-guanine phosphoribosyltransferase and adenine phosphoribosyltransferase. In vitro, the tachyzoites were cultured in the human myelomonocytic cell line THP-1, for 24 h to 96 h. Neither guanine deaminase nor hypoxanthine-guanine phosphoribosyltransferase activity was detected in 24 and 96 h cultures. In vivo, in controls and infected animals, the purine nucleoside phosphorylase and adenosine deaminase activities were the most important activities both in sera and cerebral tissue in comparison with the other activities. It was also noted that the infection modified the enzymatic activities of this purine salvage pathway, in particular, the guanine deaminase cerebral activity of infected mice was 20-fold lower than the value of controls. The treatment of mice with 2',3'-dideoxyinosine, a purine analog, at the dose of 100 mg.kg(-1).d for 30 days, induced an important increase of all enzymatic activities in the brains in comparison with control animals. These data suggest that one target of 2',3'-dideoxyinosine is the purine metabolism.

Topics: Amidohydrolases; Animals; Antimetabolites; Cells, Cultured; Cerebral Cortex; Chromatography, High Pressure Liquid; Didanosine; Female; Glycosyltransferases; Humans; Mice; Pregnancy; Purines; Toxoplasma; Toxoplasmosis, Animal; Xanthine Oxidase

The activity against Toxoplasma gondii of 2',3' dideoxyinosine (ddI), an anti-human immunodeficiency virus drug, was examined in an in vitro and in vivo study. Cell cultures infected with a strain known to cause chronic infections were used to show the dose-dependent effect of this drug compared with spiramycin and sulfadiazine. When a dose of 4 microg/ml was used, no infected THP-1 cells or parasites were found after 60 h of incubation. An electron-microscopic study confirmed that after 12 h at 1 microg/ml, the few parasites observed were severely altered. The treatment of chronically infected mice 3 months postinfection showed that a 30-day treatment with 2 mg of ddI/ml induced a significant reduction in the number of T. gondii cysts in the cerebral tissue. These cysts were not viable, as confirmed by immunofluorescence and reinfection experiments. These experiments suggest a possible role for ddI in the treatment of toxoplasmosis, and this possibility deserves further investigation.

Topics: Animals; Anti-HIV Agents; Antiprotozoal Agents; Cell Line; Cysts; Didanosine; Drug Evaluation, Preclinical; Female; Humans; Mice; Toxoplasma; Toxoplasmosis, Animal