Cisplatin-induced apoptotic cell death in Mongolian gerbil cochlea

Cisplatin is well known to cause cochleotoxicity. In order to determine the underlying mechanisms of cisplatin-induced cell death in the cochlea, we i nvestigated the apoptotic changes and the expression of bcl-2 family protei ns controlling apoptosis. Mongolian gerbils were administered 4 mg/kg/day c isplatin consecutively for 5 days. The cisplatin-treated animals showed a s ignificant deterioration in the responses of both distortion product otoaco ustic emissions and the endocochlear potential as compared with those of th e age-matched controls, suggesting outer hair cell and stria vascularis dys function. The presence of DNA fragmentation revealed by a terminal deoxynuc leotidyl transferase-mediated dUTP-biotin nick end labelling method was rec ognized in the organ of Corti, the spiral ganglion, and the stria vasculari s in the cisplatin-treated animals whereas almost negative results were obt ained in the control animals. The nuclear morphology obtained by Hoechst 33 342 staining revealed pyknotic and condensed nuclei, confirming the presenc e of the characteristic features of apoptosis. A significant increase and r eduction in the number of bax- and bcl-2-positive cells, respectively, foll owing cisplatin treatment was observed in the cells of the organ of Corti, the spiral ganglion, and the lateral wall. These findings suggest a critica l role for bcl-2 family proteins in the regulation of apoptotic cell death induced by cisplatin. The underlying mechanisms of the cisplatin-induced ce ll death are discussed. (C) 2000 Elsevier Science B.V. All rights reserved.