Oxidative metabolism in HIV-infected macrophages: role of glutathione and pharmacological approach.

Oxidative stress and glutathione deficiency seem to playa major role in the pathogenesis of HIV infection, as suggested by the increased survival of H IV-infected patients treated with N-acetylcysteine, a prodrug of glutathion e. However, beneficious effects of GSH-replenishing drugs are restricted in vivo by the high concentrations needed to obtain biological effects and th eir low bioavailability. In this study, we evaluated the antiretroviral and antioxidant activities of new more lipophilic GSH-replenishing molecules, in macrophages infected in vitro with HIV-1. In these experimental conditio ns, a prodrug of N-acetylcysteine and beta -mercaptoethylamine, I-152 demon strated a potent anti-HIV activity, increased intracellular GSH level, and decreased TNF-alpha production. Altogether these results suggest that I-152 could be beneficial as adjuvant therapy of antiretrovirals in HIV-infected patients, especially in those with damages to the central nervous system o r with mitochondrial damages associated with highly active antiretroviral t herapy. (C) 2001 Editions scientifiques et medicales Elsevier SAS.