Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals.

Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals.
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DOI:
10.1371/journal.pone.0122402
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Kumar S
Kumar S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ande A;McArthur C;Ayuk L;Awasom C;Achu PN;Njinda A;Sinha N;Rao PS;Agudelo M;Nookala AR;Simon S;Kumar A;Kumar S

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轻度至中度吸烟在艾滋病毒感染者中非常普遍,并且已知会加剧艾滋病毒的发病机制。本研究的目的是确定轻度至中度吸烟对尚未接受抗逆转录病毒治疗(ART)的hiv感染者的病毒载量、细胞因子产生、氧化应激和细胞色素P450 (CYP)途径的具体影响。招募了32名人类受试者,并将其分配到以下四个不同的队列:a) HIV阴性非吸烟者,b) HIV阳性非吸烟者,c) HIV阴性轻度至中度吸烟者,d) HIV阳性轻度至中度吸烟者。在非洲喀麦隆招募患者,使用严格的选择标准来排除尚未符合抗逆转录病毒治疗条件且未接受常规或传统药物治疗的患者。那些患有活动性肺结核、乙型肝炎或有药物滥用史的人也被排除在外。我们的研究结果显示,与不吸烟的人相比,轻度至中度吸烟的HIV阳性患者血浆中的病毒载量有所增加。此外,虽然我们没有观察到大多数促炎细胞因子水平的显著变化,但细胞因子IL-8和MCP-1在HIV感染患者和吸烟者的血浆中与HIV阴性的非吸烟者相比显着降低。重要的是,与HIV阴性的非吸烟者相比,HIV感染者和吸烟者在血浆和单核细胞中的氧化应激均显着增加。为了研究氧化应激和病毒载量增加的可能途径,我们测定了单核细胞中几种抗氧化剂和细胞色素P450酶的mRNA水平。结果显示,大多数抗氧化剂的水平没有改变,这表明它们无法对抗氧化应激。CYP2A6在吸烟者中被诱导,而CYP3A4在HIV和HIV阳性吸烟者中被诱导,与HIV阴性非吸烟者相比。总的来说,研究结果表明,在HIV阳性个体中,氧化应激和CYP途径可能与吸烟介导的病毒载量增加有关。
Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP) pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART). Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a) HIV negative non-smokers, b) HIV positive non-smokers, c) HIV negative mild-to-moderate smokers, and d) HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not yet eligible for ART and not receiving conventional or traditional medications. Those with active tuberculosis, hepatitis B or with a history of substance abuse were also excluded. Our results showed an increase in the viral load in the plasma of HIV positive patients who were mild-to-moderate smokers compared to individuals who did not smoke. Furthermore, although we did not observe significant changes in the levels of most pro-inflammatory cytokines, the cytokine IL-8 and MCP-1 showed a significant decrease in the plasma of HIV-infected patients and smokers compared with HIV negative non-smokers. Importantly, HIV-infected individuals and smokers showed a significant increase in oxidative stress compared with HIV negative non-smoker subjects in both plasma and monocytes. To examine the possible pathways involved in increased oxidative stress and viral load, we determined the mRNA levels of several antioxidant and cytochrome P450 enzymes in monocytes. The results showed that the levels of most antioxidants are unaltered, suggesting their inability to counter oxidative stress. While CYP2A6 was induced in smokers, CYP3A4 was induced in HIV and HIV positive smokers compared with HIV negative non-smokers. Overall, the findings suggest a possible association of oxidative stress and perhaps CYP pathway with smoking-mediated increased viral load in HIV positive individuals.
DOI: 10.1371/journal.pone.0035505
发表时间: 2012
期刊: PloS one
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作者:
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DOI: 10.1111/j.1530-0277.2010.01330.x
发表时间: 2011-01
期刊: Alcoholism, clinical and experimental research
影响因子: --
作者:
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