Table 4.
Non-antioxidant drug candidates for protection against CIHL
| Drug | Main mechanism of oto-protection | Experiment model | Drug dose | Route | Outcome |
|---|---|---|---|---|---|
| Dexa-methasone | Inhibiting inflammatory cytokines (PMID: 9486420) | Mice treated with dexamethasone (PMC2720789) | Cisplatin (14 mg/kg) treatment after the first dexamethasone injection | IP | Protected hearing at 16 kHz. |
| Branded as DexPak & Decadron | Dexamethasone (24 mg/ml) per day over 5 days | Intratympanic | |||
| Guinea pigs treated with dexamethasone (PMID: 21521888) | Cisplatin (12 mg/kg) | IP | Not protective. | ||
| Dexamethasone (6 mg) treatment on the day before and on the day of cisplatin treatment | Intratympanic | ||||
| Clinical trial on cancer patients (n = 26) on dexamethasone (PMID: 24618499) | Cisplatin (total 400 mg) | IP | Protected hearing at 4-8 kHz. | ||
| Dexamethasone (~8.5 mg) | Intratympanic | ||||
| Coenzyme Q10 | Anti-inflammatory dietary supplements (PMID: 35326965) | Rats treated with Coenzyme Q10 and vitamins (PMID: 27632426) | Cisplatin (4.6 mg/kg) per day for 3 days | IP | Protected hearing at 2, 4, 8, 16, 32 kHz. |
| Branded as ubiquinone & CoQ10 | Q10 terclatrate (500 mg/kg) | Oral | |||
| Acuval 400 (100 mg/kg) | Oral | ||||
| Clinical trial on cancer patients (n = 26) being treated with Coenzyme Q10 and vitamins (PMID: 28239674) | Cisplatin (100 mg/m2) every 21 days | IV | Protected hearing at 8 kHz. | ||
| Acuval Audio (1.8 g) per day starting 7 days before the first cisplatin treatment | Oral | ||||
| Statins | Inhibiting inflammatory cytokines (PMID: 35125240). | Mice treated with lovastatin (PMID: 32062294) | Cisplatin (3 mg/kg) per day for 4 days, followed by 10 days of recovery. 3 cycles (total 36 mg/kg) | IP | Protected hearing at 20, 40 kHz. |
| Branded as Lipitor & Mevacor | Lovastatin (40 mg/kg) daily from 3 days before cisplatin treatment | Oral gavage | |||
| Clinical trial on head and neck cancer patients (n = 277) on atorvastatin (PMID: 33393488) | Cisplatin (~80 mg/m2) every 3 weeks. Median cumulative cisplatin was 200 mg/m2. | Not stated | Protected hearing at 4, 6, 8, 12.5 kHz. | ||
| Atorvastatin (10~80 mg) | Oral | ||||
| HDACi | Epigenetically downregulating genes linked to apoptosis (PMID: 23558232) | Guinea pigs treated with sodium butyrate (PMID: 16467722) | Cisplatin (14 mg/kg) | IP | Protected hearing at 3.5~20 kHz, statistical significance not shown. |
| Branded as Buphenyl & Avmacol | Sodium butyrate (1.2 mg/kg) per day for 7 days before and 5 days after cisplatin treatment | IP | |||
| Rats treated with sulforaphane (PMID: 34344210) | Cisplatin (7 mg/kg) twice a day for 7 days | IP | Protected hearing at 4, 8, 16, 24, 32 kHz. OHC partially protected. | ||
| SFN (30 mg/kg) per day for 7 days | IP | ||||
| Mice treated with RG108 (PMID: 35530135) | Cisplatin (30 umol/L) | IP | Protected hearing at 8, 16, 24, 32 kHz. OHC protected seen through IHC. | ||
| RG108 (100 umol/L) 2 hours before cisplatin treatment | IP | ||||
| STAT inhibitors | Anti-inflammatory and anti-apoptosis | Rats treated with STAT1 siRNA (PMID: 21776018) | Cisplatin (11 mg/kg) | IP | Protected hearing at 8, 16, 32 kHz. OHC protected seen through electron microscopy. |
| Branded as Nifuroxazide etc | STAT1 siRNA (0.g µg) 48 hours before cisplatin treatment | Intratympanic | |||
| Rats treated with STAT1 inhibitor EGCG (PMID: 28703809) | Cisplatin (11 mg/kg) | IP | Protected hearing at 8, 16, 32 kHz. OHC protected. | ||
| EGCG (100 mg/kg) 45 minutes before cisplatin + 3 more post-cisplatin treatments | Oral | ||||
| STAT6 -/- mice (PMID: 21321603) | Cisplatin (4 mg/kg) per day for 4 days | IP | Hearing protection at 4, 16, and 32 kHz. | ||
| Cytokine inhibitors | Inhibiting inflammatory cytokines | Mice treated with flunarizine (PMID: 18584244) | Cisplatin (4 mg/kg) | IP | Reduction of cochlear TNF-a and IL-1b.No ABR recording. |
| Branded as Basiliximab, daclizumab | Sibelium (143 ug/kg) | Oral | |||
| Rats treated with etanercept (PMID: 28730299) | Cisplatin (16 mg/kg) | IP | Protected hearing at 4.5, 6, 8, 10 kHz on day 3. | ||
| Etanercept (6 mg/kg) 24 hours before cisplatin treatment | IP | ||||
| Honokiol | SIRT3-mediated antioxidant activity (PMID: 21172655) | Mice treated with honokiol (PMID: 33415008) | Cisplatin (20 mg/kg) | IP | Protected hearing at 4-32 kHz. Cisplatin cytotoxicity not affected. |
| Branded as Honobsolute | Honokiol (20 mg/kg) treatment 1 hour before cisplatin treatment |