N-acetylcysteine replenishes glutathione in HIV infection
N-acetylcysteine replenishes glutathione in HIV infection
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DOI：
10.1046/j.1365-2362.2000.00736.x
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发表时间：
2000-10-01
影响因子：
5.5
通讯作者：
Herzenberg, LA
中科院分区：
文献类型：
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作者：
De Rosa, SC;Zaretsky, MD;Herzenberg, LA
背景谷胱甘肽（GSH）缺乏在HIV感染者中很常见，并与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耗尽的GSH。这里的研究测试了口服NAC在HIV感染中安全有效地补充GSH的作用。设计在一项为期8周的随机、双盲、安慰剂对照试验中口服NAC，随后使用可选的开放标签药物长达24周。受试者HIV感染、低GSH、CD 4 T细胞< 500 L-1，没有活动性机会性感染或其他虚弱; n = 81。结果NAC组受试者的全血GSH水平从0.88 mM显著增加到0.98 mM，使NAG治疗受试者的GSH水平达到未感染对照组的89%（P = 0.03）。在为期8周的安慰剂对照试验中，安慰剂组的基线GSH水平（0.91）基本保持不变。经CD 4 T细胞计数和β 2-微球蛋白水平调整的T细胞GSH在NAG治疗的受试者中也增加（P = 0.04）。不良反应很小，并且与摄入NAC没有显着相关性。结论。NAC治疗8周可安全地恢复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，以增加对氧化应激的保护，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治疗在GSH缺乏或氧化应激在疾病病理学中起作用的其他临床情况下可能是有价值的，例如类风湿性关节炎、帕金森病、肝炎、肝硬化、败血性休克和糖尿病。
Background 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.Design Oral NAC administration in a randomized, 8-week double-blind, placebo-controlled trial followed by optional open-label drug for up to 24 weeks.Subjects 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.Results Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 mM to 0.98 mM, bringing GSH levels in NAG-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 NAG-treated subjects (P = 0.04). Adverse effects were minimal and not significantly associated with NAC ingestion.Conclusion. 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.