Table 1.
Characteristics of the antioxidants that were included in the systematic review and their main outcomes.
| References | Design | Population | Age | Gender | Treatment | Noise Exposure | Type, Dose, and Duration of Intervention | Parameters Analyzed |
|---|---|---|---|---|---|---|---|---|
| 1. Campbell (2023). Springfield (US) [36] | Prospective cohort | Chinchilla lanigera | 3–5 years | male | D-methionine | a. Steady-state noise (105 dB SPL at 4 kHz for 6 h) b. Impulse noise (155 dB 150 times × 75″) |
D-met dose levels 0, 50, 100, or 200 mg/kg/dose | a. ABR (t = 0); t (+24 h). b. Serum (GPx, Gr, SOD, and CAT) c. Cochlear enzymes (GSH/GSSG) |
| 2. Campbell (2021). Springfield [37] | D-met 200 mg/kg (5 ip injections c/12 h for 48 h) | a. ABR (t = 0); t (+21 d). b. Serum (GPx, Gr, SOD, and CAT) c. Cochlear enzymes (GSH/GSSG) |
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| 3. Campbell (2022). Springfield [38] | D-met dose levels 0, 50, 100, or 200 mg/kg/dose | a. ABR (t = 0); t (+21 d). b. Serum (GPx, Gr, SOD and CAT) c. Cochlear enzymes (GSH/GSSG) |
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| 4. Rosenhall (2019). Gothenburg (Sweden) [33] | Retrospective cohort | Personnel in Swedish armed forces | 22.9 years | both | NAC | a. Small-caliber weapons (77%) b. Large-caliber weapons (7%) |
NAC 400 mg | a. PPTA 1 (pre-exposure) b. PPTA 2 (4–72 h post-exposure) c. 9 months post-exposure |
| 5. Ada (2017). Kirklareli (Turkey) [39] | Prospective cohort | Wistar albino | - | male | 1–12 kHz band white noise; 110 dB for 6 h | NAC 100 mg/kg/day by gavage × 7 d | a. Light microscopic b. Scanning electron microscopy |
|
| 6. Choi (2014). Oklahoma City (US) [30] | RCT | Chinchilla lanigera | 3–5 years | female | NAC + 4-OHPBN oral | 4 kHz band noise; 105 dB for 6 h | NAC + 4-OHPBN oral 4 h post-noise c/12 h × 2 d | a. ABR (pre-exposure; immediately after exposure; t = +21 d) b. DPOAE c. PPTA d. Scanning electron microscopy |
| 7. Doosti (2014). Tehran (Iran) [29] | RCT | Textile workers | 39 years | male | NAC vs. ginseng | continuous noise > 85 dB for 8 h a day | 1. NAC 1200 mg/day 2. Ginseng 200 mg/day |
a. PPTA: pre-exposure and +15 d |
| 8. Lu (2014). Oklahoma (US) [28] | RCT | Long-Evans and Sprague Dawley | - | male | NAC/HPN-07 | OBN 10–20 kHz (115 dB) 1 h | Control: 5 mL/kg saline Case: NAC/HPN-07 5 mL/kg (60 mg/mL) intraperitoneally. Administration: +1 h; +2 d (×2) |
1. Plasma levels of total free cysteine and HPN-07 2. ABR; TS; DPOAE; LS a. 3–5 d before treatment b. 8 h, 24 h, 7 d, and 21 d after treatment |
| 9. Kilic (2022). Erzurum (Turkey) [31] | RCT | Sprague Dawley | - | female | Berberine | 4 kHz white noise 110 dB for 12 h | 100 mg/kg berberine single dose daily × 5 d (intragastric lavage) | a. DPOAE (before treatment; t = 6 d) b. Histopathological and immunohistochemical |
| 10. Zhao (2021). Xuzhou (China) [40] | RCT | Guinea pigs | 10–12 weeks | male | 6.3–20 kHz white noise 120 dB for 4 h (2 h noise, 8 h rest, and 2 h noise) | 5 mg/mL nanoparticle left in the RWM | a. ROS-scavenging ability (SOD and MDA) b. Inflammatory cytokines in cochlea (TNF-α, IL-6, and IL-1) c. Morpho-functional study (immunofluorescence t = +12 d and SEM) d. ABR 4, 8, 16, and 24 kHz (t = −2 d, 0 d, 2 d, 4 d, 6 d, 8 d, 10 d, 12 d, and 14 d) e. Toxicity: H&E staining t = 14 d (heart, liver, spleen, and kidney) |
|
| 11. Xiong (2017). Guangzhou (China) [41] | Prospective cohort | C57 BL/6 mice | 2 months | female | Resveratrol | 10 kHz, 120 dB for 1 h. | Resveratrol 4 g/kg for 2 months (300 mg/kg per day) | a. ABR (before treatment, end of treatment, immediately after noise exposure, and + 15 d) |
| 12. Seidman (2014). Michigan (US) [32] |
RCT | Fischer 344 | 2–3 months | male | Broadband noise, 105 dB for 24 h | 4 mg/kg resveratrol daily for 3 d by gavage | a. Cox-2 (Western blot) b. ROS in lymphocytes (fluorescence flow cytometry histogram) |
|
| 13. Chen (2020). Buffalo (US) [42] |
Prospective cohort | Sprague Dawley | 10 months | - | HK-2 | 95 dB sound pressure level (SPL) for 8 h/d for 21 days | 0.2 wt. % HK-2 corresponding to an oral dose of 125 mg/kg/day HK-2 | Compound action potential (CAP). The CAP, which reflects the gross neural output of the cochlea, was recorded for all animals approximately 2 months post-exposure |
| 14. Fetoni (2018). Rome (Italy) [43] | Prospective cohort | Wistar | adult | male | Rosmarinic acid | 60 min to a 120 dB SPL | 20 μL RA solution injected into the tympanic bulla 1 h before noise exposure RA solution (10 mg/kg) injected 1 h before noise exposure; once daily for the following 3 days |
ABR assessed bilaterally before noise exposure to ensure normal hearing and reassessed at 1, 3, 7, 15, and 30 days after noise exposure |
| 15. Richter (2018). Chicago (US) [44] | Prospective cohort | Guinea pigs | no information | - | Fluvastatin | 4–8 kHz, 120 dB re 20 μPa, for 4 h | Fluvastatin was implanted in the guinea pig’s left cochlea The pump delivered 50 μM | Frequency measured (2, 4, 8, 16, and 32 kHz) |
| 16. Zhang (2022). Beijing (China) [45] | Prospective cohort | Wistar | 2 months | male | SOD ZIF-8 | 120–125 dB for 12 h/day for 3 days | 10 μL of SOD ZIF-8; 2 mg/mL suspension | ABR in rats before drug administration, and at 1, 3, 7, 14, and 28 days after noise exposure |
| 16. Lee (2013). Oklahoma (US) [46] | Prospective cohort | CBA mice | 4 weeks | - | Ginkgo biloba | BWN (110 dB SPL) for 1 h | Gingko biloba administered once a day for 7 days before noise exposure; 3 mg/kg powder | ABR and DPOAE |
| 17. Fetoni (2012). Rome (Italy) [47] | Prospective cohort | Wistar | 2 months | - | Q10 | 100 dB (SPL) × 10 consecutive days × 60 days | Group II: Q-ter (100 mg/kg) Group III: 20 µL Q-ter Group IV: 40 µL Q-ter |
ABR at low (6, 12 kHz), mid (16, 20 kHz), and high (24, 32 kHz) frequencies ABR before noise exposure; 1, 3, 7, and 21 days after noise exposure |
| 18. Sergi (2006). Rome (Italy) [48] | Prospective cohort | Hartley albino guinea pigs | 3 months | - | IDB | Pure tone of 6 kHz for 40 min to a 120 dB SPL | Intraperitoneally: 5 mg/kg 1 h before noise exposure and once daily for the following 3 days | Electrophysiological tests: before, and +1 d, +7 d, and +21 d after noise exposure |
| 19. Fetoni (2008). Rome (Italy) [49] | Prospective cohort | 3 months | - | 40 min to a 6 kHz, 120 dB SPL | IDB (intraperitoneally: 5 mg/kg) Vitamin E (intramuscularly: 1360 IU/g) Dissolved in corn oil (10 mg/mL at 100 or 50 mg/kg body weight) |
ABR measured before noise exposure, and 1 h, 3 days, 7 days, and 21 days after noise exposure |
Abbreviations: RCT (randomized controlled trial); PTS (permanent threshold sift); TTS (temporal threshold sift); DPOAE (distortion product otoacoustic emission); ABR (auditory brainstem response); NAC (N-Acetylcysteine); Hz (Hertz); kHz (kilohertz); dB (decibels); PTTA (pure-tone threshold audiometry); RWM (round window membrane); HK-2 (1-(5-hydroxypyrimidin-2-yl) pyrrolidine-2,5-dione); IDB (idebenone); GPx (glutathione peroxidase).