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 involve d. One possible mechanism of ototoxicity might be alteration of the antioxi dant system causing an increase in free radicals. It has been demonstrated that heat shock proteins (HSPs), which are believed to protect cells by dis solving and refolding misfolded or denatured protein are induced by various form of stress. HSP is also demonstrated to be induced by free radicals. T he purpose of this study was to evaluate HSP 72 induction in cochlea follow ing 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 i njection 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 durati on 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 fro m 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 ob served 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. W ith a lethal dosage of cisplatin (20 mg/kg), HSP 72 expression was less pro minent and declined after 6 h.