Tournaire R, Arnaud S, Hamedi-Sangari F, Thomasset N, Dore JF, Vila J; International Conference on AIDS.

Int Conf AIDS. 1991 Jun 16-21; 7: 103 (abstract no. W.A.1047).

INSERM U.218, Centre Leon Berard, France

OBJECTIVE: To determine in vivo efficacy of D-ASPARTIC beta-HYDROXAMATE (DAH) against Friend Virus polycythemic strain (FVP) and to specify the biological effects of this analogue. METHODS AND RESULTS: DAH shows, when administered daily at different doses (1 to 3 g/Kg/dose) in ip injection beginning at 1-3 and 18 days post-inoculation (pi) of FVP in DBA/2 mice a marked prolongation of mean survival time. Infected mice at 3 days pi were treated with 2 g/Kg/dose of DAH (1 dose/day-8 days) and killed 16 days later. The percentage of inhibition of splenomegaly was 94%. With the same dose of DAH, a treatment beginning 18 days pi during 9 days shows a drastic regression of splenomegaly: mean spleen weight measured on day 27 pi for treated mice was 0.64 g as compared to 3.05 g for untreated mice and to 1.93 g for untreated mice on day 18 pi. The effects of DAH treatment (started 3 days pi-2 g/kg/dose x 1 dose/day-95 days) on survival of FVP infected mice and on FVP target cells: CFU-E (erythropoietic colony forming units), was analysed. Control animals had a median survival of 29 days as compared to 100 days for those treated with DAH. A transitory anemia was observed. DAH suppresses (89%-19 days pi) splenic FVP-leukemic CFU-E. Furthermore, we tested in vitro toxicity of DAH on spleen CFU-E. The preincubation for one hour with 3 mM of DAH, inhibited infected CFU-E colony formation by 23% and had no effect on uninfected CFU-E (control mice + ip phenylhydrazine) (p less than 0.02). CONCLUSION: DAH has therapeutic activity of FVP in vitro and in vivo in mice. These results suggest potential therapeutic effect in human retroviral disease.

Publication Types:

• Meeting Abstracts

Keywords:

• Anemia
• Animals
• Erythroid Progenitor Cells
• Erythropoiesis
• Friend murine leukemia virus
• Humans
• In Vitro
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Mice, Inbred Strains
• Retroviridae Infections
• Spleen
• Splenomegaly

Other ID:

• 3104791

UI: 102192239

From Meeting Abstracts