International Journal of Otolaryngology

Review Article

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

Table 2

Overview of studies performed to protect from aminoglycoside ototoxicity by antioxidants. C: Chicken, CH: Chinchilla, G: Gerbil, GP: Guinea Pig, H: Human, M: Mouse, R: Rat, ZF: Zebrafish; X: in vitro, Y: in vivo; i.m.: intramuscular, i.v.: intravenous, i.p.: intraperitoneal, i.t.: intratympanic, s.c.: subcutaneous, RWM: round window membrane; d: day, h: hour; O: no effect; P/PP/PPP: partial, not significant/partial and statistically significant/complete & statistically significant protection; T/TT/TTT: partial, not significant/partial and statistically significant/complete & statistically significant rescue.


Therapy (dose)	Aminoglycoside (dose)	Species	Outcome	Reference

Dihydroxybenzoate (100 mg/kg, 1 or 2 x/d, i.p., 21 or 26 d)	Gentamicin (120 mg/kg, 1 x/d, s.c., 19 d or 135 mg/kg, 1 x/d, s.c., 14 d)	GP	PP	[196]
Deferoxamine (100 mg/kg, 2 x/d, s.c., 28 d) Dihydroxybenzoate (100 mg/kg, 1 x/d, p.o.)	Gentamicin (120 mg/kg, 1 x/d, s.c., 19 d)	GP	PP PP	[197]
Dihydroxybenzoate (300 mg/kg, 2 x/d, 14-15 d)	Kanamycin (400–900 mg/kg, 2 x/d, s.c., 15 d)	M, Y	PP	[198]
Aspirin (0.1 or 1.0 mg/mL in drinking water, 8 d)	Amikacin (500 mg/kg, 1 x/d, i.p., 5 d)	R, Y	PP	[199]
Aspirin ( mg/d, p.o., 7 d)	Gentamicin ( mg/d, i.v., 7 d)	H	PP	[201]
Aspirin ( g/d, p.o., 14 d)	Gentamicin (total 975–986 mg i.v./patient)	H	PPP	[202]
Aspirin ( g/d, p.o., 14 d)	Gentamicin (80–160 mg, 2 x/d, i.v., 5–7 d)	H	PP	[203]
NAC (600 mg, 2 x/d, p.o., 22–25 d)	Gentamicin (2 mg/kg/d, i.v., avg. 15 d)	H	PP	[210]
D-Met (300 mg/kg/d, i.p., 28 d)	Amikacin (200 mg/kg, 1 x/d, 28 d)	GP, Y	PP	[211]
D-Met (200 mg/kg, 1-2 x/d, s.c., 19 d)	Gentamicin (120 mg/kg, 1 x/d, s.c., 19 d)	GP, Y	PP	[212]
L-NAME (100 M, 4 h)			PP	[213]
D-Met (50 mM, 4 h)	Gentamicin (2 mg/mL, 4 h)	GP, X	PP
Leupeptin (1 mM, 4 h)			PP
α-LA (100 mg/kg/d, i.m., 15 d)	Amikacin (400 mg/kg, 1 x/d, i.m., 15 d)	GP, Y	PP	[214]
Edaravone (3 mg/kg/d, i.p., 2–14 d)	Tobramycin (160 mg/kg, 1 x/d, s.c., 14 d)	R, Y	PPP, TTT	[226]
Resveratrol (10 M or 100 M, 24 h)	Gentamicin (0.4 mM, 24 h)	R, X	PP	[227]
α-Tocopherol (100 mg/kg, 1 x/d, i.m., 14 d)	Gentamicin (100 mg/kg, 1 x/d, i.m. <14 d)	GP, Y	PP	[216]
α-Tocopherol (100 mg/kg, 1 x/d, i.m., 14 d)	Gentamicin (100 mg/kg, 1 x/d, i.m. <14 d)	GP, Y	PP	[215]
α-Tocopherol (100 mg/kg, 1 x/d, i.m., 14 d)	Gentamicin (100 mg/kg, 1 x/d, i.m. <14 d)	GP, Y	PP	[217]
Glutathione (10 mM, 1 h)			PP
Dithioerythritol (10 mM, 1 h)			PP
Vitamin C (10 mM, 1 h)	Gentamicin (1 mM, 1 h)	GP, X	PP	[218]
Trolox (4 mM, 1 h)			PP
Phenylene Diamine (10 mM, 1 h)			PP
Glutathione (0.6 mL 0.3 M, p.o., 14 d)	Gentamicin (100 mg/kg, 1 x/d, i.m., 14 d)	GP, Y	PP	[228]
Ginkgo biloba (10 mg/kg, 30 min to RWM or mg/kg i.p.)	Gentamicin (5 mg/kg, 45 min to RWM or 5 mg/kg, 24 h to RWM)	GP, Y	P	[219]
Danshen (1–20 mg/kg, 2 x/d, s.c., 15 d)	Kanamycin (700 mg/kg, 2 x/d, s.c., 15 d)	M, Y	PP	[220]
Melatonin (10 mg/L in drinking water p.o., 12 d or 250 g, s.c., 1 x/d, 5–12 d)	Gentamicin (160 mg/kg, 1 x/d, i.m., 5 d) Tobramycin (200 mg/kg, 1 x/d, i.m., 5 d)	R, Y	PP	[223]
Melatonin (0.4 or 4.0 mg/kg, 1 x/d, i.p., 14 d)	Amikacin (600 mg/kg, 1 x/d, i.m., 14 d)	R, Y	P (0,4 mg)	[221]
Melatonin (0.3 l/kg, 1 x/d, i.m., 17 d)	Gentamicin (120 mg/kg, 1 x/d, i.m., 17 d)	GP, X + Y	PP	[222]
Melatonin (10, 50, 100 M, 1–7 d)	Gentamicin (1 mM, 48 h)	R, X	PP	[175]
M40403 (30 M, 24 h)	Gentamicin (0.5 or 1 mM, 24 h)	M, X	PP	[225]
Cu/Zn SOD, transgenic	Kanamycin (400 mg/kg, s.c., 10 d)	M, Y	PP	[209]
Cu/Zn SOD, transgenic Mn SOD, transgenic	Kanamycin (250 mg/kg, s.c., single dose) Ethacrynic Acid (40 mg/kg, i.v., single dose)	GP, Y	O (Cu/Zn) PP (Mn)	[224]