Assessment of the Effectiveness of Quercetin on Cisplatin-Induced Ototoxicity in Rats.

OBJECTIVES: This study aimed to evaluate the effect of quercetin on cochlear function and morphology, and its possible protective effect against acute cisplatin-induced ototoxicity in rats. MATERIALS AND METHODS: This prospective and controlled animal study was conducted on Wistar albino rats divided into four groups. Otoacoustic emission measures were performed three days after the first infiltration in Group 1 (saline), 2 (cisplatin), and 3 (quercetin). This interval was five days for Group 4 (cisplatin+quercetin). At the end of the study, the rats were decapitated with deep anesthesia, and histological changes in the cochleas were observed by light microscopy. RESULTS: Group 2 (cisplatin) revealed significant differences between the first and second measures in all frequencies. When compared to other group, the difference of the changes in Group 2 statistically significantly decreased, especially in higher frequencies. Morphologically, there were no acute changes in Group 1 and Group 3. Outer hair cell loss and the degeneration of stria vascularis and spiral ganglion were observed in both Groups 2 and 4; the damages in the latter were lesser. CONCLUSION: Quercetin does not have negative effect on cochlea, and it has protective effect on cisplatin-induced ototoxicity.

In vitro assessment of antiretroviral drugs demonstrates potential for ototoxicity.

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 âˆ¼ Trizivir >> Atripla âˆ¼ 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.

Toluene ototoxicity in rats: assessment of the frequency of hearing deficit by electrocochleography.

To identify the frequency range most sensitive to toluene-induced auditory damage, the auditory function of adult Long-Evans rats exposed to 1750 ppm of toluene (6 h/day, 5 days/week, 4 weeks), was tested by recording auditory-evoked potentials directly from the round window of the cochlea. The present electrocochleographic findings do not support a specific mid- to high-frequency loss of auditory sensitivity. On the contrary, the electrophysiologic data, obtained for audiometric frequencies ranging from 2 to 32 kHz, showed a hearing deficit not only in the mid-frequency region (12-16 kHz), but also in the mid-low-frequency region (3-4 kHz). Actually, the effect of toluene was independent of the frequency in our experimental conditions. Histological analysis was consistent with electrophysiologic data because a broad loss of outer hair cells occurred in both mid- and mid-apical coil of the organ of Corti.