Raju P A, Herzenberg L A, Herzenberg L A, Roederer M
Department of Genetics, Beckman Center B007, Stanford University Medical School, California 94305-5125.
AIDS Res Hum Retroviruses. 1994 Aug;10(8):961-7. doi: 10.1089/aid.1994.10.961.
N-Acetyl-L-cysteine (NAC) and L-2-oxothiazolidine 4-carboxylate (OTC) are pro-GSH drugs that been proposed for AIDS therapy. In this article we compare the antiviral activities of these compounds in various in vitro HIV infection models. Although both compounds blocked cytokine induction of HIV in acute and chronic infection models, and in HIV-LTR reporter cell systems, NAC was far more effective than OTC, even at suboptimal doses. To test whether this difference is due to GSH conversion efficacies of these compounds, we measured GSH restoration by NAC or OTC in GSH-depleted peripheral blood mononuclear cells (PBMCs), using flow cytometry. In isolated PBMCs, NAC fully replenishes depleted intracellular GSH whereas OTC only minimally replenishes GSH. This ability to replenish GSH in vitro and its ability to scavenge free radicals directly explain why NAC has more potent antiviral activities in vitro.
N-乙酰-L-半胱氨酸（NAC）和L-2-氧代噻唑烷-4-羧酸盐（OTC）是已被提议用于艾滋病治疗的促谷胱甘肽（GSH）药物。在本文中，我们比较了这些化合物在各种体外HIV感染模型中的抗病毒活性。尽管这两种化合物在急性和慢性感染模型以及HIV-LTR报告细胞系统中均能阻断HIV的细胞因子诱导，但即使在次优剂量下，NAC也比OTC有效得多。为了测试这种差异是否归因于这些化合物的GSH转化效率，我们使用流式细胞术测量了NAC或OTC在GSH耗竭的外周血单核细胞（PBMC）中对GSH的恢复情况。在分离的PBMC中，NAC能完全补充耗尽的细胞内GSH，而OTC只能微量补充GSH。这种在体外补充GSH的能力及其直接清除自由基的能力直接解释了为什么NAC在体外具有更强的抗病毒活性。
