N-acetylcysteine replenishes glutathione in HIV infection

Authors: De Rosa S.C.; Zaretsky M.D.; Dubs J.G.; Roederer M.; Anderson M.; Green A.; Mitra D.; Watanabe N.; Nakamura H.; Tjioe I.; Deresinski S.C.; Moore W.A.; Ela S.W.; Parks D.; Herzenberg L.A.; Herzenberg L.A.

Source: European Journal of Clinical Investigation, Volume 30, Number 10, October 2000 , pp. 915-929(15)

Publisher: Wiley-Blackwell

Abstract:

Glutathione (GSH) deficiency is common in HIV-infected individuals and is associated with impaired T cell function and impaired survival. N-acetylcysteine (NAC) is used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection.

Oral NAC administration in a randomized, 8-week double-blind, placebo-controlled trial followed by optional open-label drug for up to 24 weeks.

HIV-infected, low GSH, CD4 T cells < 500 L^-1, no active opportunistic infections or other debilitation; n = 81. Study conducted prior to introduction of protease inhibitors.

Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 mm to 0.98 mm, bringing GSH levels in NAC-treated subjects to 89% of uninfected controls (P = 0.03). Baseline GSH levels in the placebo group (0.91) remained essentially the same during the 8 week placebo-controlled trial. T cell GSH, adjusted for CD4 T cell count and 2-microglobulin levels, also increased in the NAC-treated subjects (P = 0.04). Adverse effects were minimal and not significantly associated with NAC ingestion.

NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV-infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes.

Keywords: glutathione; GSH; GSH deficiency; HIV; N-acetylcysteine; NAC,

Language: English

Document Type: Research article

Publication date: 2000-10-01

• In this: publication
• By this: publisher
• In this Subject: Public Health
• By this author: De Rosa S.C. ;  Zaretsky M.D. ;  Dubs J.G. ;  Roederer M. ;  Anderson M. ;  Green A. ;  Mitra D. ;  Watanabe N. ;  Nakamura H. ;  Tjioe I. ;  Deresinski S.C. ;  Moore W.A. ;  Ela S.W. ;  Parks D. ;  Herzenberg L.A. ;  Herzenberg L.A.

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