Increased therapeutic efficacy of zidovudine in combination with vitamin E.
Antiviral activity and bone marrow toxicity of 3'-azido-3'deoxythymidine (Zidovudine; AZT) was evaluated in the presence of alpha-D-tocopherol acid succinate (ATS) in the MT4 cell line and in murine hematopoietic progenitor cells, respectively. At varying concentrations (.016 to .125 microM) of AZT, addition of ATS (5 to 15 micrograms/ml) showed a dose-dependent increase in anti-HIV activity. The ED90 of AZT in this test system was 0.37 microM, whereas in the presence of ATS (15 micrograms/ml) it was 0.06 microM, thus producing an approximately 6-fold increase in anti-HIV activity. In contrast, in murine bone marrow cells, ATS (4 micrograms/ml) showed significant protection (p less than 0.05) against AZT-induced toxicity as measured by CFU-E and CFU-GM assays. The IC50 values in the presence and absence of ATS for CFU-E were 3.7 and 1.5 microM, whereas for CFU-GM were 6.0 and 2.7 microM, respectively. Overall, these data suggest that AZT in combination with ATS has greater therapeutic efficacy against HIV-1.
Gogu
S R
SR
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA.
Beckman
B S
BS
Rangan
S R
SR
Agrawal
K C
KC
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D006098:Granulocytes / Q000166:cytology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000166:cytology; D014779:Virus Replication / Q000187:drug effects*; D014810:Vitamin E / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology*
D014810:Vitamin E; D015215:Zidovudine