Review Article

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

Table 1

Overview of studies performed to protect from aminoglycoside ototoxicity by inhibition of apoptosis. C: Chicken, G: Gerbil, GP: Guinea Pig, M: Mouse, R: Rat, ZF: Zebrafish; X: in vitro, Y: in vivo; i.m.: intramuscular, i.p.: intraperitoneal, i.t.: intratympanic, s.c.: subcutaneous; d: day, h: hour; O: no effect, P/PP/PPP: partial, not significant/partial and statistically significant/complete and statistically significant protection.

Therapy (dose)Aminoglycoside (dose)SpeciesOutcomeReference

zVAD (100  M, 26 h)Gentamicin (0.1, 0.5, 2 mM; 24 h)C, XPPP[167]
zVAD (100  M, 26 h)PPP
BAF (100  M, 26 h)Gentamicin (1 mM, 6 & 24 h)GP +PPP[178]
Deferoxamine (1 mM, 26 h)G, XPPP
zVAD (300  M, 12 h)Neomycin (10  M, 3 h)ZFPP[179]
zVAD (local 50, 100  M or 1.5 mg/kg i.m.)Streptomycin (1.2 g/kg; 5 d, i.m.)C, Ylocal PP
i.m. P
[180]
zVAD (250  M, local @ 0.5  L/h, 14 d)
zLEHD (150  M, local @ 0.5  L/h, 14 d)
Gentamicin (12 mg/mL, local
@ 0.5  L/h, 14 d)
GP, YPP
PP
[182]
zDEVD (10 or 200  M, 48 h)PP (200 M)
zIETD (10 or 200  M, 48 h)Gentamicin (35  M, 48 h)R, XO [193]
zLEHD (10 or 200  M, 48 h)O
zVAD (100  M, 26 h)M, XPPP
zIETD (100  M, 26 h)Neomycin (1 mM, 24 h)O [166]
zLEHD (100  M, 26 h)PP
d-JNKI-1 (M 2  M; GP 10  M, 1  L/h local, 7 d)Neomycin (M 1 mM, 24–48 h; GP 300 mg/kg i.p. 5 d)M, X
GP, Y
PPP
PPP
[161]
CEP-11004 (0.5  M, 84 h)Gentamicin (50  M, 72 h)R, XPP [184]
CEP-11004 (0.2, 0.4, 1.6, 4.8  M; 7 h)Neomycin (1 mM, 3 h)C, XPP (1.6  M)[152]
CEP-11004 (1.0  M; 24 h)Neomycin (1 mM, 24 h)M, XPP[183]
Estradiol (1, 10, 100, 1000 nM; 60 h)Gentamicin (100  M, 48 h)R, XP [185]
CEP-1347 (1 mg/kg s.c., 1 x/d, 14 d)Gentamicin (120 mg/kg s.c., 1 x/d, 14 d)GP, YPP [186]
Bcl-2, transgenicNeomycin (1 mM, 24 h)M,XPP[155]
Bcl-2, transgenicGentamicin (40  g i.t., single dose)M, YPP [187]
Bcl-X(L), transgenicKanamycin (800 mg/kg, 2 x/d, s.c., 15 d)M, YPP[188]
HSP 70, transgenicNeomycin (1–4 mM, 24 h)M, XPP [191]
HSP-70, transgenicKanamycin (700 mg/kg, 2 x/d, s.c., 14 d)M, YPP[192]
HSP-70, transgenicKanamycin (700 mg/kg, 2 x/d, s.c., 14 d)M, YPP[192]