L-carnitine reduces lymphocyte apoptosis and oxidant stress in HIV-1-infected subjects treated with zidovudine and didanosine
L-carnitine reduces lymphocyte apoptosis and oxidant stress in HIV-1-infected subjects treated with zidovudine and didanosine
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DOI：
10.1089/15230860260196191
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发表时间：
2002-06-01
影响因子：
6.6
通讯作者：
De Simone, C
中科院分区：
文献类型：
--
作者：
Moretti, S;Famularo, G;De Simone, C
细胞凋亡对人类免疫缺陷病毒1 （HIV-1）感染的进展至关重要。在不影响细胞凋亡的情况下，抗逆转录病毒疗法可能无法完全控制感染，这似乎是合理的。我们分配了20名无症状hiv感染的晚期免疫缺陷患者，接受齐多夫定（AZT）和二danosine （DDI）或相同的方案加左旋肉碱（一种已知的抗凋亡药物），为期7个月。在基线和治疗15、60、120和210天后测量免疫学和病毒学参数。我们在每个时间点评估如下：(a)外周血CD4和CD8淋巴细胞凋亡的频率，CD4和CD8细胞线粒体膜电位破坏的频率，CD4和CD8细胞发生氧化应激的频率；(b)凋亡分子标志物Fas和caspase-1的表达；(c)参与细胞存活和凋亡调控的p35/cdk-5调控亚基的表达。同时检测CD4、CD8绝对计数和血浆病毒血症。与未接受左旋肉碱治疗的受试者相比，AZT和DDI加左旋肉碱治疗的受试者CD4和CD8细胞凋亡、线粒体膜电位破坏的淋巴细胞和发生氧化应激的淋巴细胞显著减少。左旋肉碱组患者淋巴细胞Fas和caspase-1下调表达，p35过表达。各组间CD4、CD8计数及病毒血症无差异。没有发现左旋肉碱的毒性。添加左旋肉碱是安全的，并且允许AZT和DDI治疗的受试者的淋巴细胞凋亡和氧化应激大大减少。
Apoptosis is critical to the progression of human immunodeficiency virus-1 (HIV-1) infection. It appears reasonable that antiretroviral therapies may not achieve a full control of the infection in the absence of an impact on apoptosis. We assigned 20 asymptomatic HIV-infected subjects with advanced immunodeficiency to receive either zidovudine (AZT), and didanosine (DDI) or the same regimen Plus L-carnitine, a known antiapoptotic drug, for 7 months. Immunologic and virologic parameters were measured at baseline and after 15, 60, 120, and 210 days of treatment. We assessed on each time point the following: (a) the frequency of peripheral blood apoptotic CD4 and CD8 lymphocytes, CD4 and CD8 cells with disrupted mitochondrial membrane potential, and CD4 and CD8 cells undergoing oxidant stress; (b) the expression of the molecular markers of apoptosis Fas and caspase-1; and (c) the expression of p35/cdk-5 regulatory subunit that is involved in regulating cell survival and apoptosis. Absolute CD4 and CD8 counts and plasma viremia were also measured. Apoptotic CD4 and CD8 cells, lymphocytes with disrupted mitochondrial membrane potential, and lymphocytes undergoing oxidant stress were greatly reduced in subjects treated with AZT and DDI Plus L-carnitine compared with those who did not receive L-carnitine. Fas and caspase-1 were down-expressed and p35 over-expressed in lymphocytes from patients of the L-carnitine group. No difference was found in CD4 and CD8 counts and viremia between the groups. No toxicity Of L-carnitine was recognized. The addition Of L-carnitine is safe and allows apoptosis and oxidant stress to be greatly reduced in lymphocytes from subjects treated with AZT and DDI.