ANTIOXIDANT STATUS AND LIPID-PEROXIDATION IN PATIENTS INFECTED WITH HIV

ANTIOXIDANT STATUS AND LIPID-PEROXIDATION IN PATIENTS INFECTED WITH HIV
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DOI:
10.1016/0009-2797(94)90037-x
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发表时间:
1994-06-01
影响因子:
5.1
通讯作者:
MICOUD, M
MICOUD, M
中科院分区:
医学2区
文献类型:
--
作者:
FAVIER, A;SAPPEY, C;MICOUD, M

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艾滋病患者体内存在抗氧化性微量营养素缺乏。这些观察只涉及一些孤立的营养物质,表明锌、硒和谷胱甘肽存在缺陷。在这些患者中也发现了自由基产生和脂质过氧化的增加,这一点非常重要,最近的论文提出了一种免疫缺陷,更重要的是,由于自由基的过度产生,继发于HIV-1复制的增加。我们评估了不同的研究,试图获得这些患者抗氧化状态的全球视角。在成人中,我们观察到锌、硒和维生素E的水平随着疾病的严重程度而逐渐下降,但硒在II期保持正常。然而,主要的戏剧性下降与类胡萝卜素有关,其水平在II期仅为正常值的一半。为了了解这些抗氧化剂的减少和氧化应激的增加是继发于疾病的恶化还是相反,我们对渐近患者进行了纵向调查。给出了本次评价的初步结果。矛盾的是,II期的脂质过氧化程度高于IV期。这可能与无症状阶段更多活性的中性粒细胞(PMN)产生更强烈的氧自由基相一致。自由基的产生和脂质过氧化似乎次要于病毒对PMN的刺激和细胞因子的分泌。在细胞培养中,N-乙酰半胱氨酸或抗坏血酸被证明能够阻断氧化应激后HIV-1的表达,N-乙酰半胱氨酸在体外抑制肿瘤坏死因子诱导的感染细胞的凋亡。关于所有这些实验数据,很少有抗氧化剂在艾滋病毒感染患者中进行认真和大规模的试验,尽管已经进行了一些使用锌或硒的初步研究。在我们看来,现在是时候评估抗氧化剂对人体的有益作用了。当与N-乙酰半胱氨酸结合时,更有希望呈现协同效应的候选者似乎是β-胡萝卜素、硒和锌。
Deficiency in antioxidant micronutrients have been observed in patients with AIDS. These observations concerning only some isolated nutrients demonstrate a defect in zinc, selenium, and glutathione. An increase in free radical production and lipid peroxidation has been also found in these patients, and takes a great importance with recent papers presenting an immunodeficiency and more important an increase in HIV-1 replication secondary to free radicals overproduction. We have assessed different studies, trying to obtain a global view of the antioxidant status of these patients. In adults we observe a progressive decrease for zinc, selenium, and vitamin E with the severity of disease, except that selenium remains normal at stage II. However, the main dramatic decrease concerns carotenoids whose level at stage II is only half the normal value. To understand if these decreases in antioxidant and increases in oxidative stress occur secondary to the aggravation of the disease or, conversely, are responsible for it, we undertook a longitudinal survey of asymptotic patients. The: preliminary results of this evaluation are presented. Paradoxically, lipid peroxidation is higher at stage II than at stage IV. This may be consecutive to a more intense overproduction of oxygen free radicals by more viable polymorphonuclear (PMN) at the asymptomatic stage. The free radicals production and lipid peroxidation seem secondary to a direct induction by the virus of PMN stimulation and cytokines secretion. N-Acetyl cystein or ascorbate have been demonstrated in cell culture to be capable of blocking the expression of HIV-1 after oxidative stress and N-acetyl cysteine inhibits in vitro TNF-induced apoptosis of infected cells. In regard to all these experimental data, few serious and large trials of antioxidants have been conducted in HIV-infected patients, although some preliminary studies using zinc or selenium have been performed. In our opinion it is now time to evaluate in humans the beneficial effect of antioxidants. The more promising candidates for presenting synergistic effects when associated with N-acetyl cysteine seem to be beta-carotene, selenium and zinc.