Antiretroviral effect of combined zidovudine and reduced glutathione therapy in murine AIDS.
A combination of antiretroviral drugs acting at different points in the virus replication cycle was evaluated in a murine retrovirus-induced immunodeficiency model of AIDS (MAIDS). Intramuscular administration of high doses of reduced glutathione (GSH, 100 mg/mouse/day) and AZT (0.25 mg/ml in drinking water) was found to reduce lymphoadenopathy (92%), splenomegaly (80%), and hypergammaglobulinemia (90%) significantly more than AZT alone. Combined treatment resulted in a reduction in proviral DNA content of 69, 66, and 60%, respectively, in lymph nodes, spleen, and bone marrow. Furthermore, the stimulation index of B cells was also significantly higher in animals receiving GSH and AZT whereas additional responses were not observed in the T cell stimulation index and blood lymphocyte phenotype analyses. In conclusion, the administration of high doses of GSH and AZT, a new combination of antiviral drugs, seems to provide additional advantages compared to single-agent therapy.
Magnani
M
M
Institute of Biological Chemistry Giorgio Fornaini, University of Urbino, Italy. magnani@bib.uniurb.it
Fraternale
A
A
Casabianca
A
A
Schiavano
G F
GF
Chiarantini
L
L
Palamara
A T
AT
Ciriolo
M R
MR
Rotilio
G
G
Garaci
E
E
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000302:isolation & purification; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005978:Glutathione / Q000627:therapeutic use*; D006403:Hematologic Tests; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000473:pathology; D011533:Proviruses / Q000235:genetics; D015215:Zidovudine / Q000627:therapeutic use*
D000998:Antiviral Agents; D004279:DNA, Viral; D015215:Zidovudine; D005978:Glutathione