Baur A, Harrer T, Peukert M, Jahn G, Kalden J R, Fleckenstein B
Institut für Klinische und Molekulare Virologie der Universität Erlangen-Nürnberg.
Klin Wochenschr. 1991 Oct 2;69(15):722-4. doi: 10.1007/BF01649442.
Alpha-lipoic acid, a naturally occurring disulfide-compound that acts as a cellular coenzyme, inhibits replication of HIV-1 in cultured lymphoid T-cells. Alpha-lipoic acid was added 16 hours after infection of the T-cell lines Jurkat, SupT1 and Molt-4 with HTLV IIIB and HIV-1 Wal (a wild type HIV-1 isolate). We observed a dose dependent inhibition of HIV-1-replication in CPE (Cytopathic effect) formation, reverse transcriptase activity and plaque formation on CD4-transformed HeLa-cells. An over 90% reduction of reverse transcriptase activity could be achieved with 70 micrograms alpha-lipoic acid/ml, a complete reduction of plaque-forming units at concentrations of greater than or equal to 35 micrograms alpha-lipoic acid/ml. An augmentation of the antiviral activity was seen by combination of zidovudine and low dose of alpha-lipoic acid (7 micrograms/ml). Trypan blue staining revealed no toxic effects of alpha-lipoic acids on peripheral blood mono-nuclear cells and T-cell lines even in concentrations of greater than or equal to 70 micrograms/ml. Therefore, we propose the inclusion of alpha-lipoic acid into chemotherapy trials in combination with zidovudine.
α-硫辛酸是一种天然存在的二硫化物化合物,作为一种细胞辅酶,可抑制HIV-1在培养的淋巴细胞中的复制。在用HTLV IIIB和HIV-1 Wal(一种野生型HIV-1分离株)感染T细胞系Jurkat、SupT1和Molt-4 16小时后添加α-硫辛酸。我们观察到在CPE(细胞病变效应)形成、逆转录酶活性以及在CD4转化的HeLa细胞上的噬斑形成方面,HIV-1复制受到剂量依赖性抑制。70微克α-硫辛酸/毫升可使逆转录酶活性降低超过90%,浓度大于或等于35微克α-硫辛酸/毫升时噬斑形成单位完全减少。齐多夫定与低剂量α-硫辛酸(7微克/毫升)联合使用可增强抗病毒活性。台盼蓝染色显示,即使在浓度大于或等于70微克/毫升时,α-硫辛酸对外周血单核细胞和T细胞系也没有毒性作用。因此,我们建议将α-硫辛酸与齐多夫定联合纳入化疗试验。