Glutathione depletion in HIV-infected patients: role of cysteine deficiency and effect of oral N-acetylcysteine.
OBJECTIVE
To determine whether a single oral dose of N-acetylcysteine corrects the deficiency of cysteine and glutathione in plasma and mononuclear cells of HIV-infected patients.


METHODS
Pharmacokinetic and pharmacodynamic study.


METHODS
Cysteine and glutathione were measured in plasma and peripheral blood mononuclear cells of patients at different stages of HIV infection before and after a single oral dose of N-acetylcysteine.


RESULTS
At baseline, the plasma concentrations of glutathione and cysteine were significantly lower in HIV-infected patients than in healthy controls. The intracellular concentration of glutathione correlated with the absolute CD4 lymphocyte counts: the concentration of glutathione in mononuclear cells was significantly lower in patients with more advanced immunodeficiency. A single oral dose of N-acetylcysteine increased the concentration of cysteine in plasma and mononuclear cells of HIV-infected patients. Four hours after N-acetylcysteine administration, intracellular glutathione concentrations in the patients were moderately higher than at baseline and at 2 h.


CONCLUSIONS
Oral N-acetylcysteine transiently increases the concentrations of cysteine and glutathione in mononuclear cells of patients with HIV infection. A sustained increase in intracellular cysteine may be necessary to normalize intracellular glutathione. This may be accomplished by repeat administration of N-acetylcysteine.
de Quay
B
B
Department of Clinical Pharmacology and Medizinische Poliklinik, University of Bern, Switzerland.
Malinverni
R
R
Lauterburg
B H
BH
D000111:Acetylcysteine / Q000494:pharmacology*; D000284:Administration, Oral; D003545:Cysteine / Q000097:blood / Q000172:deficiency* / Q000187:drug effects; D005978:Glutathione / Q000097:blood / Q000172:deficiency* / Q000187:drug effects; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male
D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine