In聽vitro assessment of antiretroviral drugs demonstrates potential for ototoxicity

详细信息    查看全文

• 作者：Pru Thein¹ ; Gilda M. Kalinec¹ ; Channy Park ; Federico Kalinec ; ^{fkalinec@mednet.ucla.edu" class="auth_mail}
• 关键词：FACS ; fluorescence activated cell sorting ; NRTI ; nucleoside analogue reverse transcriptase inhibitor ; NNRTI ; non-nucleoside reverse transcriptase inhibitor ; PI ; protease inhibitor ; HAART ; High-Activity Anti-Retroviral Therapy
• 刊名：Hearing Research
• 出版年：April, 2014
• 年：2014
• 卷：310
• 期：Complete
• 页码：27-35
• 全文大小：2549 K

文摘

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鈩? Combivir鈩? Epzicom鈩? Trizivir鈩? and Truvada鈩? 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聽鈭悸燭rizivir聽>>聽Atripla聽鈭悸燙ombivir聽>聽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.