| Autor: |
Aincy, M., Coyat, C., Diot, S., Marie, A., Flaszka, E., Defosse, F., Souchal, M., Baudoux, V., Vincent, C., Dewavrechin, M., Pucheu, S., Naert, G. |
| Předmět: |
|
| Zdroj: |
Journal of Hearing Science; Sep2024, Vol. 14 Issue 3, p103-103, 1/3p |
| Abstrakt: |
Ouabain is a cardiac glycoside acting as a Na+/K+-ATPase inhibitor. It is widely used in the treatment of congestive heart failure and arrythmia, but currently less used due to its narrow therapeutic index. Several animal studies demonstrated ouabain's ototoxicity, its contribution to spiral ganglion neuron (SGN) loss and subsequent hearing loss. The objective of this study was to compare various methods of ouabain administration in the middle and inner ear to characterize its ototoxic effects in guinea pigs. Different routes of administration and doses of ouabain were tested: 1, 3 and 10 mM administered via round window injection (RWI), a round window membrane deposit (RWM) or transtympan-ic administration (TT). Several parameters were assessed, from the injection volumes (5, 10, 20 µL), to the injected ear (L/R) and the repetition of administration (up to 3 times). Specific care was provided to the treated guinea pigs with consideration to hydration and food supplementation. ABR thresholds and DPOAE amplitudes were measured between baseline (BL) and T+7DAYS or T+14DAYS to evaluate hearing impairments. These functional measures were correlated with histological analyses, SGN counts, inner hair cell (IHC) and outer hair cell (OHC) counts. Both RWI and RWM, at 3 and 10 mM, induced important hearing loss demonstrated by a significant increase of ABR thresholds followed by considerable SGN loss. Moreover, a decrease of DPOAE amplitudes and some inflammatory processes were observed, even at the lowest dose of all the ouabain administrations. Interestingly, IHC and OHC numbers were similar after a 1 mM ouabain injection whereas DPOAE amplitudes dramatically decreased. However, a 1 mM dose of ouabain administered via TT generated a decrease of DPOAE amplitudes, without affecting ABR thresholds and neither the SGN nor the HC count. Apart from the TT ouabain administration, all the tested approaches generated various health issues, such as major weight loss, ear necrosis, rectal prolapse and high mortality. Ultimately, ouabain administration in the middle or inner ear of guinea pigs is ototoxic with heterogenous results, not limited to SGN loss. Concomitantly, most of the tested routes of administration generated variable health issues. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
