INHIBITION OF MURINE AIDS BY REDUCED GLUTATHIONE

The imbalance of the redox state in cells and body fluids in HIV-1-inf ected patients may result in progression of the disease as well as in immunologic disfunctions. In this report, we have evaluated whether th e direct administration of high doses of reduced glutathione (GSH) exe rts any antiviral activity and/or improves immune functions in a murin e immunodeficiency animal model, Intramuscular administration of 50 or 100 mg GSH/mouse for five consecutive days weekly to LP-BM5-infected mice did not show local or systemic signs of acute toxicity, During th e first 3 weeks from infection, a period in which clinical signs of di sease were not yet detectable, GSH significantly reduced the viral loa d in lymph nodes and spleen as evaluated by a PCR semiquantitative ass ay of the proviral DNA content, At 10 weeks a GSH concentration-depend ent reduction of splenomegaly, lymphadenopathy and hypergammaglobuline mia was evident in all treated mice. Evaluation of proviral DNA conten t showed that GSH was effective in inhibiting LP-BM5 infectivity in ly mph nodes, spleen, and bone marrow at 100 mg/day, while it was less ef fective when administered at 50 mg/day, At 10 weeks some animals recei ving the highest GSH dose died, thus only the mice receiving 50 mg GSH were followed up to 15 weeks without signs of toxicity, In this case, almost not significant differences among infected untreated or treate d animals were observed. Thus, GSH is effective in reducing the provir al DNA load in the first period of infection, These data and the failu re of sulfhydril supplementation to further counteract the progression of disease after 10 weeks of infection suggest that combinations of G SH and other antiviral agents may be useful for improving current anti viral therapies.