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Protective effect of melatonin against gentamicin ototoxicity

Published online by Cambridge University Press:  28 October 2008

L-F Ye
Affiliation:
Department of Otolaryngology, Zhongnan Hospital of Wuhan University, Hubei, People's Republic of China
Z-Z Tao*
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Hubei, People's Republic of China
Q-Q Hua
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Hubei, People's Republic of China
B-K Xiao
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Hubei, People's Republic of China
X-H Zhou
Affiliation:
Department of Otolaryngology, Zhongnan Hospital of Wuhan University, Hubei, People's Republic of China
J Li
Affiliation:
Department of Otolaryngology, Zhongnan Hospital of Wuhan University, Hubei, People's Republic of China
Y-L Yuan
Affiliation:
Department of Anatomy, School of Medicine, Wuhan University, Hubei, People's Republic of China
*
Address for correspondence: Dr ZeZhang Tao, Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, PR China. Fax: 862767812892 E-mail: [email protected]

Abstract

Objective:

To research the protective effect of melatonin against gentamicin ototoxicity.

Methods:

Guinea pigs were randomly divided into four groups. The first group received intramuscular gentamicin (120 mg/kg body weight/day) for 17 days. Over the same time period, a second group simultaneously received intramuscular gentamicin (120 mg/kg body weight/day) plus (on the other side) intramuscular melatonin (0.3 ml kg body weight/day). Two groups of controls were treated for 17 days with either intramuscular melatonin or intramuscular saline. After the 17 days, each animal underwent distortion product otoacoustic emission testing (both ears). The guinea pigs were sacrificed by decapitation just after the final injection. Their cochleae were used to produce a tissue section, surface preparation and scanning electron microscope preparation.

Results:

Distortion product otoacoustic emission testing indicated gentamicin-induced hearing loss at 3, 4, 6 and 8 kHz in gentamicin-treated animals. Animals receiving melatonin co-therapy had significantly attenuated hearing loss and their cochleae showed lower rates of outer hair cell loss (comparing the same cochlear turns), compared with gentamicin-treated animals (p < 0.01).

Conclusion:

These findings confirm the occurrence of outer hair cell loss after gentamicin treatment, and the attenuation of such loss following simultaneous melatonin injection, using the method of morphological evaluation. These results suggest that melatonin protects against gentamicin ototoxicity by interfering with cytotoxic mechanisms.

Type
Main Articles
Copyright
Copyright © JLO (1984) Limited 2008

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References

1 Williams, SE, Zenner, HP, Schacht, J. Three molecular steps of aminoglycoside ototoxicity demonstrated in outer hair cells. Hear Res 1987;30:1118CrossRefGoogle ScholarPubMed
2 Schacht, J. Antioxidant therapy attenuates aminoglycoside induced hearing loss. Ann N Y Acad Sci 1999;884:125–30Google ScholarPubMed
3 Sha, SH, Schacht, J. Prevention of aminoglycoside induced hearing loss. Keio J Med 1997;46:115–19CrossRefGoogle ScholarPubMed
4 Priuska, EM, Schacht, J. Formation of free radicals by gentamicin and iron and evidence for an iron/gentamicin complex. Biochemical Pharmacology 1995;50:1749–52CrossRefGoogle ScholarPubMed
5 Roland, PS. New developments in our understanding of ototoxicity. Ear Nose Throat J 2004;83:1516CrossRefGoogle ScholarPubMed
6 Reiter, RJ, Guerrero, JM, Garcia, JJ, Acuna-Castroviejo, D. Reactive oxygen intemediates, molecular damage, and aging, Relation to melatonin. Ann N Y Sci 1998;854:410–24CrossRefGoogle Scholar
7 Ye, L, Xiao, B, Hua, Q, Tao, Z, Huang, Z, Zhou, X. Research on DPOAE of guinea pigs under awake and anesthetic conditions [in Chinese]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2004;21:625–7Google ScholarPubMed
8 Garetz, SL, Altschuler, RA, Schacht, J. Attenuation of gentamicin ototoxicity by glutathione in the guinea pig in vivo. Hear Res 1994;77:81–7CrossRefGoogle ScholarPubMed
9 Kalkandelen, S, Selimoglu, E, Erdogan, F, Ucuncu, H, Alats, E. Comparative cochlear toxicities of streptomycin, gentamicin, amikacin and netilmicin in guinea-pigs. J Int Med Res 2002;30:406–12CrossRefGoogle ScholarPubMed
10 Lesniak, W, Pecoraro, VL, Schacht, J. Ternary complexes of gentamicin with iron and lipid catalyze formation of reactive oxygen species. Chem Res Toxicol 2005;18:357–64CrossRefGoogle ScholarPubMed
11 Sha, SH, Schacht, J. Formation of reactive oxygen species following bioactivation of gentamicin. Free Radical Biol Med 1999;26:341–7CrossRefGoogle ScholarPubMed
12 Lesniak, W, Harris, WR, Yudenfreud-Kraviz, J, Schacht, J, Pecoraro, VL. Solution chemistry of copper(II)-gentamicin complexes. Relevance to metal-related aminoglycoside toxicity. Inorg Chem 2003;42:1420–9CrossRefGoogle ScholarPubMed
13 Thalmann, R, Kusakari, I, Miyoshi, T. Dysfunction of energy releasing and consuming processes of the cochlea. Laryngoscope 1973;83:1690–712CrossRefGoogle ScholarPubMed
14 Clerici, WJ, Hensley, K, Dimartino, DL, Butterfield, DA. Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explants. Hear Res 1996;98:116–24CrossRefGoogle ScholarPubMed
15 Tan, DX, Manchester, LC, Reiter, RJ, Qi, WB, Karbownik, M, Calvo, JR. Significance of melatonin in antioxidative defence system: reactions and products. Biol Signals Recept 2000;9:137–59CrossRefGoogle ScholarPubMed
16 Reiter, RJ, Tan, DX, Cabrera, J, D'Arpa, D, Sainz, RM, Mayo, JC, Ramos, S. The oxidant/antioxidant network: role of melatonin. Biol Signals Recept 1999;8:5663CrossRefGoogle ScholarPubMed