TABLE 1.
Antioxidant protection against gentamicin ototoxicity, assessed in vivo, is inconsistent across agents and across reports. All values reported in this table were extracted from published figures as cited; in some cases, threshold shift was calculated by subtracting baseline threshold from post-gentamicin thresholds
| Species | Gentamicin (GM) insult | Protective agent (drug and dosing) | Average threshold shift in control subjects | Average threshold shift in treated subjects | |
|---|---|---|---|---|---|
| Garetz et al. (1994)a | Pigmented guinea pig | 100 mg/kg/days × 14 days | 0.6 ml of 0.3 M glutathione (GSH) (oral gavage) | 42 dB at 2 kHz 60 dB at 8 kHz 70 dB at 18 kHz |
25 dB at 2 kHz 38 dB at 8 kHz* 40 dB at 18 kHz* |
| Sha and Schacht (1999b) | Pigmented guinea pig | 120 mg/kg/days × 19 days | 100 mg/kg sodium salicylate, s.c., BID | 38 dB at 3 kHz 42 dB at 9 kHz 62 dB at 18 kHz |
15 dB at 3 kHz* 20 dB at 9 kHz* 20 dB at 18 kHz |
| Lopez-Gonzalez et al. (2000) | Wistar rats | 160 mg/kg/days × 5 days | 10 mg/L melatonin in drinking water | DPOAE amplitude decreased by 21.5 dB at 6 kHz | DPOAE amplitude decreased by 3 dB at 6 kHz |
| 250 μg/day melatonin s.c. | DPOAE amplitude decreased by 5 dB at 6 kHz | ||||
| 250 μg/day melatonin i.m. | DPOAE amplitude decreased by 6.5 dB at 6 kHz | ||||
| Sha and Schacht (2000) | Pigmented guinea pig | 120 mg/kg/days × 19 day | 200 mg/kg d-methionine QD s.c. | 38 dB at 3 kHz 47 dB at 9 kHz 45 dB at 18 kHz |
8 dB at 3 kHz* 29 dB at 9 kHz* 32 dB at 18 kHz |
| 200 mg/kg d-methionine BID s.c./i.p. | 38 dB at 3 kHz 40 dB at 9 kHz 40 dB at 18 kHz |
20 dB at 3 kHz 28 dB at 9 kHz* 20 dB at 18 kHz* |
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| Ylikoski et al. (2002) | Albino guinea pig | 120 mg/kg/days × 14 days | 1 mg/kg/day Cephalon (CEP-1347, s.c.) × 29 days, starting 1 day pre-GM | 62 dB at 2 kHz 75 dB at 4 kHz 78 dB at 8 kHz 80 dB at 16 kHz 60 dB at 32 kHz |
4 dB at 2 kHz* 30 dB at 4 kHz* 48 dB at 8 kHz* 53 dB at 16 kHz* 50 dB at 32 kHz* |
| Fetoni et al. (2003) | Albino guinea pig | 100 mg/kg/days × 14 days | 100 mg/kg vitamin E (dl-a-tocopherol) i.m. | 25 dB at 2 kHz 30 dB at 4 kHz 50 dB at 8 kHz 48 dB at 12 kHz 56 dB at 16 kHz |
10 dB at 2 kHz* 15 dB at 4 kHz* 24 dB at 8 kHz* 28 dB at 12 kHz* 27 dB at 16 kHz* |
| Fetoni et al. (2004) | Albino guinea pig | 100 mg/kg/days × 14 days | 100 mg/kg vitamin E (dl-a-tocopherol) i.m. | 35 dB at 2 kHz 38 dB at 4 kHz 55 dB at 8 kHz 56 dB at 12 kHz 66 dB at 16 kHz |
10 dB at 2 kHz* 14 dB at 4 kHz* 27 dB at 8 kHz* 30 dB at 12 kHz* 34 dB at 16 kHz* |
| Okuda et al. (2005) | Albino guinea pig | 12 mg/ml gentamicin delivered intra-cochlear at 0.5 μl/h × 14 days | 250 μM z-VAD-FMK (general caspase inhibitor) delivered intra-cochlear at 0.5 μl/h × 14 days | 37 dB at 8 kHz | 17 dB at 8 kHz* |
| 250 μM z-LEHD-FMK (caspase 9 inhibitor) delivered intracochlear at 0.5 μl/h × 14 days | 21 dB at 8 kHz* | ||||
| Nordang and Anniko (2005) | Sprague–Dawley rats | 20 μl of 480 mg/ml GM on days 0, 1 and 3, injected through tympanic membrane | 1 mg of l-NAME with GM | 5 dB at 12 kHz 15 dB at 16 kHz 35 dB at 20 kHz 40 dB at 35 kHz |
0 dB at 12 kHz 0 dB at 16 kHz −2 dB at 20 kHz −5 dB at 35 kHz |
| Sha et al. (2006) | Human | 80–160 mg/day × 5–7 days, twice daily | 3 g/day aspirin × 14 days, divided into 3 doses/day | 13 % had ≥15 dB shift at both 6 and 8 kHz | 3 % had ≥15 dB shift at both 6 and 8 kHz* |
| Kharkheli et al. (2007) | Human | 80 mg 3 times/day × 7 days | 2,800 mg Vitamin E, divided into 3 doses/day (1,200 mg, 800 mg, 800 mg) | 3.40 % had ≥20 dB shift two adjacent frequencies ; 10.3 % had ≥15 dB shift two adjacent frequencies; 13.8 % had ≥10 dB shift two adjacent frequencies |
13.0 % had ≥20 dB shift two adjacent frequencies ; 8.7 % had ≥15 dB shift two adjacent frequencies; 10.4 % had ≥10 dB shift two adjacent frequencies |
| Ye et al. (2009)b | Pigmented guinea pig | 120 mg/kg/day × 17 days | 0.3 ml/kg melatonin i.m. | DPOAE amplitude decreased by: 6 dB at 3 kHz 10 dB at 4 kHz 13 dB at 6 kHz 11 dB at 8 kHz |
DPOAE amplitude decreased by: 2 dB at 3 kHz* 4 dB at 4 kHz* 5 dB at 6 kHz* 4 dB at 8 kHz* |
| Pfannenstiel et al. (2009) | C57BL/6 mice | 1 μl of 40 μg/μl gentamicin sulfate applied to RWM | Adenovector-expressing human bcl-2 (Ad.11D.bcl-2) delivered to posterior semicircular canal |
21 dB at 4 kHz 13 dB at 8 kHz 18 dB at 16 kHz 24 dB at 32 kHz |
−1 dB at 4 kHz 3 dB at 8 kHz −2 dB at 16 kHz 2 dB at 32 kHz* |
| Behnoud et al. (2009) | Human | 240 mg/day × 7 days (administered as 80 mg every 8 h) | 1.5 g/day Aspirin | 1.1 dB at 250 Hz* 1.6 dB at 500 Hz* 1.7 dB at 1000 Hz* 5.1 dB at 2000 Hz* 9.3 dB at 4000 Hz* 13.3 dB at 8000 Hz* 37 % had ≥15 dB shift at 4 kHz; 20 % had ≥15 dB shift at 8 kHz |
0.7 dB at 250 Hz 0.9 dB at 500 Hz 1.9 dB at 1000 Hz 2.7 dB at 2000 Hz 5.0 dB at 4000 Hz* 6.0 dB at 8000 Hz* 3 % had ≥15 dB shift at 4 kHz; 3 % had ≥15 dB shift at 8 kHz |
| Choung et al. (2011) | Sprague–Dawley rats | 160 mg/kg × 5 days (i.p.) | 500 mg/kg/day Korean Red Ginseng × 12 days (starting 7 days pre-GM) | 9 dB at 16 kHz 9 dB at 32 kHz |
5 dB at 16 kHz 5 dB at 32 kHz* |
| Bas et al. (2012) | Wistar rats | 10 mg in 200 μl saline in mini-pump, or 10 mg in 40 μl saline on RWM using gelfoam | Dexamethasone | (Click Stimuli) Mini-pump: 30 dB Gelfoam: 31 dB |
Mini-pump: 5 dB* Gelfoam: 0 dB * |
| Melatonin | Mini-pump: 10 dB* Gelfoam: 5 dB* |
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| Tacrolimus | Mini-pump: 0 dB* Gelfoam: 0 dB* |
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| Uzun et al. (2012) | Wistar rats | 120 mg/kg × 16 days (i.p.) | 4 % garlic diet (pulverized whole clove) | 61 dB at 10 kHz | 27 dB at 10 kHz* |
| Fetoni et al. (2012) | Albino guinea pig | 100 mg/kg × 14 days (i.p.) | Q-ter, 100 mg/kg (i.p.), 1 h pre-gentamicin | 20 dB at 2 kHz 27 dB at 4 kHz 35 dB at 6 kHz 36 dB at 8 kHz 47 dB at 12 kHz 45 dB at 16 kHz 39 dB at 20 kHz |
10 dB at 2 kHz* 20 dB at 4 kHz* 24 dB at 6 kHz* 26 dB at 8 kHz* 26 dB at 12 kHz* 27 dB at 16 kHz* 25 dB at 20 kHz* |
| Jankauskas et al. (2012) | Outbred white rats | 160 mg/kg × 6 days (i.p.) | SkQR1, 100 nmol/kg 3 h pre-gentamicin | Preyer reflex, average score = 2.5 Score based on sound level where reflex first observed: 0 = reflex absent (deaf) 1 = high level (severe hearing reduction); 2 = moderate level (moderate hearing decrease) 3 = low level (hearing intact) |
Preyer reflex, average score = 2.9* |
| Tian et al. (2013) | Sprague–Dawley rats | 500 mg/ml × 20 μl, intratympanic | 500 mg/kg/day Korean Red Ginseng × 21 day (starting 7 days pre-GM) | 32 dB at 16 kHz 29 dB at 32 kHz |
22 dB at 16 kHz* 20 dB at 32 kHz* |
| Ojano-Dirain et al. (2013) | Albino guinea pig | 130 mg/kg × 10 days (s.c.) | MitoQ, 0.03 g/L in drinking water for duration of study (~85 days) | 36 dB at 4 kHz 45 dB at 8 kHz 57 dB at 16 kHz |
21 dB at 4 kHz* 30 dB at 8 kHz* 48 dB at 16 kHz* |
aSurvival rate—7 of 13 gentamicin controls, 6 of 12 glutathione plus gentamicin animals
bSurvival rate—13 of 18 gentamicin controls, 13 of 15 glutathione plus gentamicin animals
*p < 0.05, significant reduction in threshold shift for between group comparisons as reported by authors with the exception of Behnoud et al. (2009) who reported the statistical reliability of threshold changes within groups. Aspirin-treated human patients had statistically significant threshold shifts at fewer frequencies than those receiving placebo