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 (3 × 500 mg/d, p.o., 7 d) | Gentamicin (3 × 80 mg/d, i.v., 7 d) | H | PP | [201] |
| Aspirin (3 × 1 g/d, p.o., 14 d) | Gentamicin (total 975–986 mg i.v./patient) | H | PPP | [202] |
| Aspirin (3 × 1 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 μM, 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 μM or 100 μM, 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 1 × 100 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 μg, 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 μM, 1–7 d) | Gentamicin (1 mM, 48 h) | R, X | PP | [175] |
| M40403 (30 μM, 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] |