Protective effect of acetyl- l-carnitine against oxidative stress induced by antiretroviral drugs

• Published in: FEBS letters 2006-12, Vol.580 (28), p.6612-6616
• Main Authors: Ferraresi, Roberta, Troiano, Leonarda, Roat, Erika, Nemes, Elisa, Lugli, Enrico, Nasi, Milena, Pinti, Marcello, Calvani, Menotti, Iannuccelli, Maurizio, Cossarizza, Andrea
• Format: Article
• Language: English
• Subjects: Acetyl- l-carnitine; Acetylcarnitine - pharmacology; ALC; Anti-HIV Agents - adverse effects; Apoptosis; Apoptosis - drug effects; AZT; d4T; ddI; didanosine; Flow Cytometry; H2O2; HAART; high active anti-retroviral therapy; Human immunodeficiency virus; Humans; hydrogen peroxide; Hydrogen Peroxide - metabolism; Membrane Potentials - drug effects; Mitochondrial membrane potential; Mitochondrial Membranes - drug effects; NRTIs; nucleosidic reverse transcriptase inhibitors; O 2; Oxidative Stress - drug effects; ROS; stavudine; superoxide anion; U937 Cells; zidovudine; ΔΨ m
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2006.11.016

Both HIV infection per se and antiretroviral drugs might contribute to oxidative stress and mitochondrial dysfunctions. In this study we assess zidovudine, stavudine and didanosine on U937 and CEM cell lines. All these drugs induced apoptosis and increased intracellular hydrogen peroxide but not superoxide anions. The addition of acetyl- l-carnitine (ALC) was able to prevent the pro-oxidant effect of the drugs tested. Supplementation with ALC, deficient in certain cohorts of HIV-infected individuals, especially on high active antiretroviral therapy regimen, has been associated with favourable effects. These data suggest that one of these effects could be a direct anti-oxidant action.