Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs.
Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs.
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DOI：
10.3390/jcm10214824
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发表时间：
2021-10-20
影响因子：
3.9
通讯作者：
Molès JP
中科院分区：
文献类型：
--
作者：
Durand M;Nagot N;Nhu QBT;Vallo R;Thuy LLT;Duong HT;Thanh BN;Rapoud D;Quillet C;Tran HT;Michel L;Tuyet TNT;Hai OKT;Hai VV;Feelemyer J;Perre PV;Jarlais DD;Minh KP;Laureillard D;Molès JP
抗病毒核苷类似物（ANA）是新近使用的抗丙型肝炎病毒（HCV）的治疗剂。众所周知，这类药物对线粒体DNA（mtDNA）表现出毒性。注射毒品的人（PWID）特别受HCV感染和HIV治疗（抗逆转录病毒药物，ARV）和其他非法药物累积的有丝分裂毒性药物暴露的影响。本研究旨在探讨直接作用抗病毒药物（DAA）治疗对PWID患者mtDNA的影响。共有470名积极注射海洛因使用者被纳入。我们使用全血定量PCR来确定每个细胞的线粒体拷贝数（MCN）和线粒体DNA缺失的比例（MDD）。在DAA治疗前后评估这些参数。HCV治疗后MDD显著增加，而MCN无差异。当受试者同时接受抗逆转录病毒治疗时，MDD甚至更高。在多变量分析中，我们发现多暴露于DAA和每日注射海洛因或定期消费甲基苯丙胺与高MCN丢失呈正相关，而DAA和ARV治疗或美沙酮使用被确定为mtDNA缺失的危险因素。这些观察结果值得关注，因为它们以前与细胞过早老化或细胞转化有关，因此需要长期随访。
Antiviral nucleoside analogues (ANA) are newly used therapeutics acting against the hepatitis C virus (HCV). This class of drug is well known to exhibit toxicity on mitochondrial DNA (mtDNA). People who inject drugs (PWID) are particularly affected by HCV infection and cumulated mitotoxic drug exposure from HIV treatments (antiretrovirals, ARV) and other illicit drugs. This study aims to explore the impact of direct-acting antiviral (DAA) treatments on mtDNA among PWID. A total of 470 actively injecting heroin users were included. We used quantitative PCR on whole blood to determine the mitochondrial copy number per cell (MCN) and the proportion of mitochondrial DNA deletion (MDD). These parameters were assessed before and after DAA treatment. MDD was significantly increased after HCV treatment, while MCN did not differ. MDD was even greater when subjects were cotreated with ARV. In multivariate analysis, we identified that poly-exposure to DAA and daily heroin injection or regular consumption of methamphetamines were positively associated with high MCN loss while DAA and ARV treatments or methadone use were identified as risk factors for having mtDNA deletion. These observations deserve attention since they were previously associated with premature cell ageing or cell transformation and therefore call for a long-term follow-up.
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线粒体转录和RNA聚合酶II依赖性核转录对抗病毒核糖核苷的敏感性。
影响因子：
6.7
作者：
Arnold JJ;Sharma SD;Feng JY;Ray AS;Smidansky ED;Kireeva ML;Cho A;Perry J;Vela JE;Park Y;Xu Y;Tian Y;Babusis D;Barauskus O;Peterson BR;Gnatt A;Kashlev M;Zhong W;Cameron CE
通讯作者：
Cameron CE
影响因子：
4.6
作者：
Belmonte FR;Martin JL;Frescura K;Damas J;Pereira F;Tarnopolsky MA;Kaufman BA
通讯作者：
Kaufman BA
影响因子：
4.5
作者：
Meyer JN;Leuthner TC;Luz AL
通讯作者：
Luz AL
影响因子：
1.4
作者：
Hashad, Doaa I.;Elyamany, Amany S.;Salem, Perihan E.
通讯作者：
Salem, Perihan E.
影响因子：
4.8
作者：
Johnson, AA;Ray, AS;Johnson, KA
通讯作者：
Johnson, KA