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
Department of Genetics, Stanford University, USA.
Eur J Clin Invest. 2000 Oct;30(10):915-29. doi: 10.1046/j.1365-2362.2000.00736.x.
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 micro 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 beta2-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.
谷胱甘肽（GSH）缺乏在HIV感染者中很常见，并且与T细胞功能受损和生存受损有关。N-乙酰半胱氨酸（NAC）用于补充因对乙酰氨基酚过量而消耗的GSH。本研究测试口服NAC在HIV感染中安全有效地补充GSH的效果。
在一项随机、为期8周的双盲、安慰剂对照试验中口服NAC，随后可选择进行长达24周的开放标签药物治疗。
HIV感染者，GSH水平低，CD4 T细胞<500 μL-1，无活动性机会性感染或其他衰弱情况；n = 81。研究在蛋白酶抑制剂引入之前进行。
NAC组受试者的全血GSH水平从0.88 mM显著增加至0.98 mM，使NAC治疗的受试者的GSH水平达到未感染对照的89%（P = 0.03）。在为期8周的安慰剂对照试验期间，安慰剂组的基线GSH水平（0.91）基本保持不变。经CD4 T细胞计数和β2-微球蛋白水平校正后的T细胞GSH在NAC治疗的受试者中也有所增加（P = 0.04）。不良反应轻微，且与摄入NAC无显著关联。
NAC治疗8周可安全地补充HIV感染者的全血GSH和T细胞GSH。因此，NAC提供了有用的辅助治疗，以增强对氧化应激的保护、改善免疫系统功能并增加对乙酰氨基酚和其他药物的解毒作用。这些发现表明，NAC疗法在其他GSH缺乏或氧化应激在疾病病理中起作用的临床情况中可能具有价值，例如类风湿性关节炎、帕金森病、肝炎、肝硬化、感染性休克和糖尿病。
