Expression of heat shock protein 72 in rat cochlea with cisplatin-induced acute ototoxicity.
Cisplatin ototoxicity is known to involve mainly the organ of Corti. Outer hair cells (OHCs). especially in the basal turn, are preferentially involved. One possible mechanism of ototoxicity might be alteration of the antioxidant system causing an increase in free radicals. It has been demonstrated that heat shock proteins (HSPs), which are believed to protect cells by dissolving and refolding misfolded or denatured protein are induced by various form of stress. HSP is also demonstrated to be induced by free radicals. The purpose of this study was to evaluate HSP 72 induction in cochlea following cisplatin injection in the animal model. Sprague-Dawley (SD) rats were injected intraperitoneally with normal saline as control or cisplatin at a dose of 5, 10 or 20 mg/kg. Cochleae were harvested 1, 3, 6 and 12 h after injection and compared with those of controls. Immunocytochemical study with surface preparation and Western blotting were performed to investigate the expression of HSP 72. Auditory brainstem response (ABR) was also recorded to assess functional change according to the dosage of cisplatin and duration after injection. In the 5 and 10 mg/kg groups, immunostaining for HSP 72 in the OHCs reached a plateau level at 3 h, which was maintained until 12 h after injection. The amount of immunoreactive OHCs in the 20 mg/kg group was smaller than those in 5 and 10 mg/kg groups and declined after 6 h. The bands for HSP 72 became less intense as the cisplatin dosage increased from 5 to 10 and 20 mg/kg in Western blotting. The change in ABR threshold was small in the 5 and 10 mg/kg groups and a marked change in threshold was observed in the 20 mg/kg group. Detection of HSP 72 after cisplatin injection could confirm the OHCs as one of the major injured cells in the cochlea. With a lethal dosage of cisplatin (20 mg/kg), HSP 72 expression was less prominent and declined after 6 h.
Oh
S H
SH
Department of Otolaryngology, Seoul National University College of Medicine, Korea.
Yu
W S
WS
Song
B H
BH
Lim
D
D
Koo
J W
JW
Chang
S O
SO
Kim
C S
CS
D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005609:Free Radicals; D050884:HSP72 Heat-Shock Proteins; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008297:Male; D009925:Organ of Corti / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005609:Free Radicals; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D002945:Cisplatin