Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

Table 3

Overview of studies with alternative strategies to protect from aminoglycoside ototoxicity. C: Chicken, CH: Chinchilla, G: Gerbil, GP: Guinea Pig, M: Mouse, R: Rat, X: in vitro, Y: in vivo; i.m.: intramuscular, i.v.: intravenous, i.p.: intraperitoneal, i.t.: intratympanic, s.c.: subcutaneous; d: day, h: hour, q12 h: every 12 h; O: no effect; P/PP/PPP: partial, not significant/partial and statistically significant/complete and statistically significant protection.

Therapy (dose)	Aminoglycoside (dose)	Species	Outcome	Reference
BDNF (10 ng/mL, 4 h)	Gentamicin (2 mg/mL, 4 h)	GP, X	PP	[213]
Dizocilpine (1 mg/kg/d, osmotic pump, 14 d); Ifenprodil (10 mg/kg/d, osmotic pump, 14 d)	Neomycin (50 mg/kg, 1 x/d, s.c., 14 d) or; Kanamycin (250 mg/kg, 1 x/d, s.c., 21 d)	GP, Y	PP; PP	[233]
Dizocilpine (1 mg/kg, 1 x/d, s.c.,10 d)	Streptomycin (400 mg/kg, 1 x/d, s.c., 10 d)	R, Y	PP	[234]
CTNF (0.44 g/kg, 1 x/d, s.c., 30 d)	Gentamicin (80 mg/kg, 1 x/d, i.m., 30 d)	GP, Y	PP	[249]
BDNF (1 𝜇g, pellet in semicircular canal, with AG or 1 week later, over 1–8 weeks)	Gentamicin (50 𝜇g, pellet in semicircular canal, over 1–8 weeks)	CH, Y	P; TT	[246]
BDNF (100 𝜇g/mL, local, pump @ 0.25 𝜇L/h, 30 d); NT-3 (100 𝜇g/mL, local, pump @ 0.25 𝜇L/h, 30 d)	Kanamycin (400 mg/kg, 1 x/d, i.p., 5 d)	GP, Y	O (BDNF); PP (NT-3)	[248]
L-NAME (100 𝜇M, 8 h); BDNF (10 ng/mL, 8 h)	Gentamicin (2 mg/mL, 8 h)	GP, X	PP; PP	[247]
Isosorbide (1 mM, 8 h)	Gentamicin (2 mg/mL, 8 h)	GP, X	PP	[255]
MK 801 (1 mg/kg, 3 x before pump implantation) +/− NT-3 (local in pump @ 300 ng/h over 14 d)	Amikacin (300 mM, local pump @ 5 𝜇L/h, 24 h)	GP, Y	P (MK 801); PP (MK + NT)	[256]
GDNF (10 𝜇M, 72–96 h)	Neomycin (0.6 mM, 72 h)	R, X	P (X)	[250]
GDNF (50 ng/mL, local pump @ 0.5 𝜇L/h or single dose 0.1 mg, i.t.)	Kanamycin (200 mg/kg, s.c., single dose) + Ethacrynic Acid (40 mg/kg, i.v., single dose)	GP, Y	PP (Y)
GDNF + TGF-1, transgenic	Kanamycin (150 mg/kg, s.c., single dose) + Ethacrynic Acid (40 mg/kg, i.v., single dose)	GP, Y	PP	[257]
GDNF, transgenic	Gentamicin (8 mg, i.t., single dose)	GP, Y	PP	[258]
GDNF, transgenic	Kanamycin (200 mg/kg, s.c., single dose) + Ethacrynic Acid (40 mg/kg, i.v., single dose)	GP, Y	PP	[259]
Gentamicin (10 mg/kg, 1 x/d, i.m., 30 d)	Gentamicin (160 mg/kg, 1 x/d, i.m., 10 d)	GP, Y	PP	[230]
Amikacin (20 mg/kg, 1 x/d, i.m., 30 d)	Amikacin (400 mg/kg, 1 x/d, i.m., 10 d)	GP, Y	PP	[231]
2 Octave-band noise (81 dB SPL for 21 d)	Gentamicin (445 𝜇g, local to RWM over 14 d)	G, Y	P	[232]
Ethacrynic Acid (40 mg/kg, i.v., single dose, 12–18 h )	Gentamicin (125 mg/kg, 1–20 injections q12h, i.m.)	GP, Y	PP	[252]