Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms.
Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms.
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DOI：
10.1111/j.1460-9568.2010.07355.x
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Levine JD
中科院分区：
文献类型：
--
作者：
Ferrari LF;Levine JD
人类免疫缺陷病毒/获得性免疫缺陷综合征（HIV/AIDS）化疗（如核苷逆转录酶抑制剂（NRTI））的主要剂量限制性副作用是由其线粒体毒性介导的小纤维疼痛性周围神经病变。合并症也可能导致艾滋病毒/艾滋病治疗的剂量限制效应。酗酒本身也会产生疼痛性神经病变，是HIV/AIDS患者周围神经病变的最重要的共病风险因素之一。尽管这一问题的流行及其对HIV/AIDS患者的生活质量和持续治疗的严重影响，酒精滥用加剧高效抗逆转录病毒治疗（HAART）诱导的神经性疼痛的机制尚未得到证实。在这项研究中，在大鼠中进行，我们研究了细胞机制，其中消耗酒精影响抗逆转录病毒诱导的神经性疼痛。NRTI 2 '，3'-双脱氧胞苷（ddC）（50 mg/kg）引起的神经病变为线粒体依赖性而非PKCε依赖性，酒精引起的痛性神经病变为PKCε依赖性而非线粒体依赖性。在低剂量下，单独不影响伤害感受的ddC（5 mg/kg）和酒精（6.5%乙醇饮食一周）一起产生深刻的机械性痛觉过敏。这种痛觉过敏是线粒体依赖性的，但不依赖于PKCε。这些实验，这提供了第一个模型，用于研究疼痛性神经病变的共病的影响，支持的临床印象，酒精消费增强艾滋病毒/艾滋病治疗神经病变，并提供证据的线粒体机制的作用，这种相互作用。
A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC) (50 mg/kg) neuropathy was mitochondrial dependent and PKCε independent, and alcohol-induced painful neuropathy, PKCε dependent and mitochondrial independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for one week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial dependent but PKCε independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction.
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影响因子：
6.9
作者：
Dew, MA;Becker, JT;Banks, G
通讯作者：
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影响因子：
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作者：
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作者：
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作者：
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通讯作者：
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DOI：
10.15288/jsa.2002.63.179
发表时间：
2002-03-01
期刊：
JOURNAL OF STUDIES ON ALCOHOL
影响因子：
--
作者：
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通讯作者：
Shapiro, M