In vitro assessment of antiretroviral drugs demonstrates potential for ototoxicity.
In vitro assessment of antiretroviral drugs demonstrates potential for ototoxicity.
复制标题
DOI：
10.1016/j.heares.2014.01.005
复制
发表时间：
2014-04
期刊：
影响因子：
2.8
通讯作者：
Kalinec, Federico
中科院分区：
文献类型：
--
作者：
Thein, Pru;Kalinec, Gilda M.;Park, Channy;Kalinec, Federico
几项研究报告说，艾滋病毒/艾滋病患者中听力障碍的发生率增加。我们在细胞存活率、流式细胞仪和caspase3/7激活研究中使用听觉性HEI-Oc1细胞，研究了14种艾滋病毒抗逆转录病毒药物的潜在耳毒性：阿巴卡韦、氮卓酮、地诺辛、伊法韦林、恩曲他滨、依地那韦、拉米夫定、奈非那韦、奈维拉平、替诺福韦、利托那韦、斯塔夫定和扎西他滨，以及这些药物的组合，用于常见的抗艾滋病毒鸡尾酒Atripla™、Combivir™、Epzicom™、Trizivir™和Truvada™。我们的结果表明，大多数单一的抗HIV药物对HEI-OC1听觉细胞是有毒性的。另一方面，鸡尾酒降低了听觉细胞的活性，其严重程度依次为：Epzicom~Trizivir≫Atripla~Combivir&Gt；Truvada。有趣的是，我们的结果表明，Trizivir和Epzicom诱导的细胞死亡可能是由caspase非依赖的机制介导的。L-卡尼汀是一种天然微量营养素，已知可以保护HEI-OC1细胞免受一些耳毒性药物的攻击，并减少与抗艾滋病毒治疗相关的神经病变，拉米夫定、替诺福韦以及鸡尾酒Atripla处理的细胞活力增加，但对其他药物和药物组合处理的细胞只有轻微影响。总之，这些结果表明，一些经常使用的抗HIV药物可能会对患者的听力产生有害影响，并为旨在阐明当前和未来抗HIV药物的潜在耳毒性的进一步研究提供了论据。
Several studies have reported an increased incidence of auditory dysfunction among HIV/AIDS patients. We used auditory HEI-OC1 cells in cell viability, flow cytometry and caspases 3/7-activation studies to investigate the potential ototoxicity of fourteen HIV antiretroviral agents: Abacavir, AZT, Delavirdine, Didenosine, Efavirenz, Emtricitabine, Indinavir, Lamivudine, Nefinavir, Nevirapine, Tenofovir, Ritonavir, Stavudine and Zalcitabine, as well as combinations of these agents as used in the common anti-HIV cocktails Atripla™, Combivir™, Epzicom™, Trizivir™, and Truvada™. Our results suggested that most of the single assayed anti-HIV drugs are toxic for HEI-OC1 auditory cells. The cocktails, on the other hand, decreased auditory cells’ viability with high significance, with the following severity gradient: Epzicom ~ Trizivir ≫ Atripla ~ Combivir > Truvada. Interestingly, our results suggest that Trizivir- and Epzicom-induced cell death would be mediated by a caspase-independent mechanism. L-Carnitine, a natural micronutrient known to protect HEI-OC1 cells against some ototoxic drugs as well as to decrease neuropathies associated with anti-HIV treatments, increased viability of cells treated with Lamivudine and Tenofovir as well as with the cocktail Atripla, but had only minor effects on cells treated with other drugs and drug combinations. Altogether, these results suggest that some frequently used anti-HIV agents could have deleterious effects on patients hearing, and provide arguments in favor of additional studies aimed at elucidating the potential ototoxicity of current as well as future anti-HIV drugs.
登录
查看更多内容
影响因子：
7.2
作者：
Parrish, Amanda B.;Freel, Christopher D.;Kornbluth, Sally
通讯作者：
Kornbluth, Sally
影响因子：
2.8
作者：
Bektas, Devrim;Martin, Glen K.;Lonsbury-Martin, Brenda L.
通讯作者：
Lonsbury-Martin, Brenda L.
影响因子：
158.5
作者：
Riddler, Sharon A.;Haubrich, Richard;Mellors, John W.
通讯作者：
Mellors, John W.
影响因子：
1.6
作者：
Kalinec, GM;Webster, P;Kalinec, F
通讯作者：
Kalinec, F
影响因子：
6.6
作者：
Moretti, S;Famularo, G;De Simone, C
通讯作者：
De Simone, C