[Sensitivity to the ototoxicity of kanamycin of the rat model for mimetic aging in the inner ear].
OBJECTIVE
To research the animal model with mimetic aging effect in the inner ear predispose to the ototoxicity of kanamycin.


METHODS
Fifty wistar rats were randomly divided into four groups: group A (D-galactose group, n = 14) were treated with hypodermic 5% D-galactose (150 mg x kg(-1) x d(-1)) for 8 weeks and then with intraperitoneal saline for 10 days; group B (D-galactose and kanamycin group, n = 14) were given the same dose of D-galactose but kanamycin (500 mg x kg(-1) x d(-1)) instead of saline; group C (kanamycin group, n = 12) were treated with saline for 8 weeks and then with intraperitoneal kanamycin for 10 days;group D (control group, n = 10) were given saline only. Auditory brainstem response (ABR) was used to detect the hearing threshold of rats and colorimetry was used to analyze the activity of the GSH-PX. The inner ear tissue was harvested and the mitochondrial DNA was amplified to identify the 4834 bp deletion mutation by nested primer polymerase chain reaction (nested PCR) technique.


RESULTS
The incidence of mitochondrial DNA 4834 bp deletion mutation was 100% (28/28) in group A, 92.86% (26/28) in group B and 0% in group C or group D. The activity of GSHPX in group A was (59.07 +/- 8.70)U, (63.29 +/- 12. 40)U in group B, (136.67 +/- 9.53)U in group C and (142.10 +/- 7.02)U in group D. The difference between group A and D was significant (P = 0.000) while the difference between group A and B was not significant (P = 0.307), which was similarly as between group C and group D (P = 0.151). ABR threshold was (5.36 +/- 3.08) dB peSPL in group A, (61.79 +/- 11.20) dB peSPL in group B, (34.17 +/- 4.69) dB peSPL in group C and (6.50 +/- 3.37) dB peSPL in group D. No difference was found between group A and D (P = 0.398) while the difference in shift of ABR threshold between group B and group C (or group D) was significant (P = 0.000).


CONCLUSIONS
The mimetic aging effect in the inner ear of the rat can be induced by D-galactose, and these rats present high incidence of mtDNA4834 deletion which can greatly enhance the sensitivity of the inner ear to the kanamycin.
Hu
Yu-Juan
YJ
Department of Otorhinolaryngology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Kong
Wei-Jia
WJ
Wang
Qiong
Q
Xu
Li
L
Wang
Ying
Y
Han
Yue-Chen
YC
Kong
Wen
W
D019588:Aging, Premature / Q000139:chemically induced*; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D007758:Ear, Inner / Q000187:drug effects*; D005690:Galactose / Q000633:toxicity; D007612:Kanamycin / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017384:Sequence Deletion
D004272:DNA, Mitochondrial; D007612:Kanamycin; D005690:Galactose