کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4355139 1615590 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vitro assessment of antiretroviral drugs demonstrates potential for ototoxicity
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی سیستم های حسی
پیش نمایش صفحه اول مقاله
In vitro assessment of antiretroviral drugs demonstrates potential for ototoxicity
چکیده انگلیسی


• In vitro studies suggest that several common anti-HIV drugs are likely ototoxic.
• Cocktails used in High-Activity Anti-Retroviral Therapy are toxic for HEI-OC1 cells.
• Anti retrovirals-induced cell death was associated with caspase-independent mechanisms.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Hearing Research - Volume 310, April 2014, Pages 27–35
نویسندگان
, , , ,