de Araujo et al. 1717 de Araujo JG, Serra LSM, Lauand L, Kückelhaus SAS, Sampaio ALL. Protective effect of melatonin on cisplatin-induced ototoxicity in rats. Anticancer Res. 2019;39:2453-8. (2019) |
32 Rodents-Rat Wistar/female 3 months old. |
4 Groups - Groups – control saline (1 mg/kg): 5 rat/control melatonin (1 mg/kg): rats/cisplatin (10 mg/kg) + melatonin (1 mg/kg): 12 rats/cisplatin (10 mg/kg) + melatonin (1 mg/kg): 10 rats |
8 days (D1 and D8) – DPOAE |
D1 - (DPOE) no differences between the four groups/D8 - lower values on group cisplatin + saline compared to the saline group at all frequencies. The results did no differ between the saline and melatonin or cisplatin + melatonin groups. |
Bas et al.2727 Bas E, Van De Water TR, Gupta C, Dinh J, Vu L, Martínez-Soriano F, et al. Efficacy of three drugs for protecting against gentamicin-induced hair cell and hearing losses. Br J Pharmacol. 2012;166:1888-904. (2012) |
25 Rodents-Rat Wistar/male, age not mentioned |
In vivo: groups: S (MP: 200 mL of saline; gelfoam: 40 mL of saline); GM (MP: 10 mg pf GM in 200 mL of saline; gelfoam: 10mgof GM in 40 mL of saline); GM + DXM; GM + MLT; GM+ TCR (MP: 10 mg of GM and DXM, MLT or TCR (MP: 10 mg of GM and DXM, MLT or TCR respectively, with each at 500 mM final concentration in 200 mL of saline; gelfoam: 10mgof GM and DXM, MLT or TCR, respectively, with each at 500 mM final concentration in 40 mL of saline |
In vivo studies: 21 days |
In vivo: DPOAE – cochlear treated with saline had values that were similar to the base line values that were obtained before the onset of treatment. Ears treated with GM had a decrease on days 10, 15, 21. No significant differences between basal levels and DPOAE for GM + DXM; GM + MLT and GM + TCR. ABR-S-treated ears only showed a significant elevation in threshold in the gelfoam treatment group at 10 days post-treatment and then a return to a pretreatment threshold at 15 days post-treatment, while cochleae treatment with GM by either gelfoam or via a MP showed significant increases (p < 0.05) in ABR threshold with respect to their baseline values on post-treatment days 10-20. In the GM+DXM; GM + MLT and GM + TCR treated groups, the ABR threshold values were similar to those values recorded for the S-treated ears with only a transient elevation in thresholds in the MP GM+ DXM, Group at 10 days and in the MP GM + TCR group at 15 days post- treatment. Cytocochleogram. Analysis of the cochleograms constructed from the hair cell counts taken from the organ of Corti FITC phalloidin-stained surface preparations from the five groups of animals indicate a loss of OHCs in the mid- to high-frequency regions of the cochlear treated with GM while the cochleae treated with saline lost very few auditory sensory cells. Treatment of cochleae with GM did not affect IHCs viability in the mid- to high-frequency regions, the treatment of GM-exposed cochleae with either DXM, MLT or TCR prevented most of the GM exposure-induced OHC losses. |
Demir et al.2626 Demir MG, Altıntoprak N, Aydın S, Kösemihal E, Başak K. Effect of transtympanic injection of melatonin on cisplatin-induced ototoxicity. J Int Adv Otol. 2015;11:202-6. (2015) |
24 Rodents-Rat Wistar/male, age not mentioned |
3 Groups: control group – single dose of intraperitoneal saline (12 mg/kg) for 5 days and 0.1 cc transtympanic saline for 5 days. Group 2: single dose of intraperitoneal cisplatin (12 mg/kg) and 0.1 cc transtiympanic saline for 5days. Group 3: single dose of intraperitoneal cisplatin (12 mg/kg) and 0.1 mg/mL transtimpanic melatonin for 5 days. |
11 days: ABR -realized one day prior to the study and 10 days after the cisplatin dose/EOA -realized on the first day of the study and 10 days after the cisplatin dose. |
DPOAE – values and threshold shift at DPOAE were calculated. Group 1 – had significant better thresholds in all frequencies than Group 2. Group 1 and Group 3 did not have any significant differences on acoustic values. Group 3 had significantly smaller decreases at high frequencies than Group 2 ABR values Group 3 had better ABR click at 4000, 60,000 and 8000 Hz; no differences between Group 1 and 3. Pathologic results: no significant differences between the groups. However, when comparing the means, there is less cilia loss and epithelial loss in Group 3 than Group 2 |
Erdem et al.1919 Erdem T, Ozturan O, Iraz M, Miman MC, Olmez E. Dosedependent dual effect of melatonin on ototoxicity induced by amikacin in adult rats. Eur Arch Otorhinolaryngol. 2005;262:314-21. (2005) |
44 Rodents – Sprague Dawley-Rat com 12 month age |
5 Groups all substances intra – penitonially; control group: vehicle: 4 rats; melatonin group (4mg/kg/day): 4 rats; amikacin group (600 kg/day): 12 rats amikacin + low dose melatonin (0.4mg/kg/day) group: 12 rats; amikacin + high dose melatonin (4mg/kg/day) group: 12 rats |
DPOAE measurements: day 0, day 5, day 10, day 15 |
Groups control and melatonin - not significant changes from DPOA. amikacin group - DP GRAM not affected during the study. Amikacin ototoxicity findings in I/O function detected on the 10 days. No differences between day 10 and 15 Group AML: no statistically significant differences in DP-GRAM in the whole study Group AMH: the DP gram and I/O functions amplitude were reduced, and I/O thresholds were increased by means of high dose melatonin administration of amikacin |
Lopez-Gonzalez et al.2323 Lopez-Gonzalez MA, Guerrero JM, Torronteras R, Osuna C, Delgado F. Ototoxicity caused by aminoglycosides is ameliorated by melatonin without interfering with the antibiotic capacity of the drugs. J Pineal Res. 2000;28:26-33. (2000) |
180 Rodents – Wistar Female Rat two months old 20 in each group |
9 Groups - Group 1: control; Group 2: gentamicin (200 mg/kg); Group 3: tobramycin (160 mg/kg; Group 4: gentamicin + SC melatonin (250 μg); Group 5: tobramycin + SC melatonin; Group 6: gentamicin + IM (250 μg) melatonin; Grupo 7: tobramicin + IM melatonina (250 μg); Group 8: gentamicin + DR melatonina; Group 9: tobramycin + DW (10mg/L) melatonin |
5 days - day 1/day 3/day 5 - DPOEA antibiogram |
Group 1: control: no significant differences in DPOEA pre and pos treatment. Group 2: gentamicin: Significant differences on DPOEA, pre and post treatment. Group 3: tobramycin: less significant differences comparing to the groups with gentamicin and gentamicin + melatonin. No significant differences between the groups that received melatonin in difference ways of administration. The antibiograms showed that the efficacy of the aminoglycosides was not affected by the use of melatonin. |
Lopez-Gonzalez et al.2424 Lopez-Gonzalez MA, Guerrero JM, Rojas F Delgado F. Ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants. J Pineal Res. 2000;28:73-80. (2000) |
140 Rodents – Wistar Female Rat two months old 20 in each group |
7 Groups - Group 1: control; Group 2: solvents and melatonin: Group 3: cisplatin; Group 4: cisplatin + melatonin DW (10mg/L), Group 5: cisplatin + melatonin SC (250 Μ); Group 6: cisplatin + antioxidant mixture; Group 7: cisplatin + melatonin SC+ antioxidant. |
DPOEA: day 0, day 7, day 15 |
Day 7 pos-treatment: decrease with values from animals treated with cisplatin and a more moderate decrease in the animals treat with the combined therapies day 15 post-treatment: decrease values in group treated with cisplatin. The groups treated with cisplatin + melatonin or other antioxidant mixture presented values to the group control. |
Ye et al.2525 Ye L-F, Tao Z-Z, Hua Q-Q, Xiao B-K, Zhou X-H, Li J, et al. Protective effect of melatonin against gentamicin ototoxicity. J Laryngol Otol. 2009;123:598-602. (2009) |
54 Guinea pigs age and sex not mentioned |
4 Groups: Group 1–13 animals, gentamicin (120mg/kg/day); Group 2: 13 animals: gentamicin (120 mg/kg/day) + melatonin (0.3mL/kg/day); Group 3: 11 animals: melatonin (0.3mL/kg/day); Group 4: 11 animals: saline. |
17 days of injection and then was realized DPOAE. Histologic evaluation. |
17 days of injection and then was realized DPOAE. Group 3 and 4 melatonin and saline – stable hearing at all of the DPOAE. group of gentamicin showed the expected hearing loss between 3 and 8 kHz. Animals treat with gentamicin + melatonin showed reduced lower hearing loss at all frequencies, compared with gentamicin group, this difference was statistically significant at 3, 4, 6 and 8 kHz. Cochlear histopathology showed melatonin treatment exert a protective effect on the outer cells. The group of gentamicin showed almost complete loss of outer hair cells. Histologic results showed that there was a more significant loss of outers cells in Group 1 than Group 2. Loss of cells in Group 3 was similar to the Group 2. |