[The role of mtDNA deletion in the sensitivity to aminoglycoside antibiotic induced deafness].
OBJECTIVE
To establish an animal model of mitochondrial DNA (mtDNA) deletion and investigate the possible role of mtDNA deletion in aminoglycoside antibiotic induced deafness.


METHODS
Thirty wistar rats (4 months) were randomly divided into group A and B. Doxorubicin (DOX) was subcutaneously injected at doses of 2 mg/kg twice per week for 3 months in group A and then kanamycin (KM) was intraperitoneally injected 500 mg/kg per day for 10 consecutive days. The treatments of group B were identical to group A, except normal saline was substituted for DOX. The thresholds of auditory brainstem response (ABR) were measured before and after the drug administrations. The inner ear membranous labyrinthine tissue was harvested and mtDNA was amplified to identify 4,834 bp deletion by PCR technique.


RESULTS
The elevation of the mean ABR thresholds in group A(67.08 +/- 8.59) dB peSPL was significantly higher than that in group B (12.71 +/- 4.42) dB peSPL after KM administration (P < 0.001). In group A, 9 of the 15 rats demonstrated 4,834 bp mtDNA deletion. However, mtDNA 4,834 bp deletion was negative in group B animals.


CONCLUSIONS
DOX can induce mtDNA deletion in the inner ear tissue of the rat. mtDNA deletion in the inner ear may play an important role in the hypersensitivity to aminoglycoside antibiotic ototoxicity.
Kong
W
W
Department of Otorhinolaryngology, Union Hospital of Tongji Medical University, Wuhan 430022, China. weijiak@public.wh.hb.cn
Liu
J
J
Dong
J
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics*; D003638:Deafness / Q000139:chemically induced / Q000235:genetics; D004317:Doxorubicin / Q000633:toxicity; D007758:Ear, Inner / Q000187:drug effects*; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D017353:Gene Deletion; D007612:Kanamycin / Q000633:toxicity*; D008297:Male; D009154:Mutation; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D004272:DNA, Mitochondrial; D007612:Kanamycin; D004317:Doxorubicin