CASPASE INHIBITORS PREVENT CISPLATIN-INDUCED APOPTOSIS OF AUDITORY SENSORY CELLS

IN VITRO studies tested the efficacy of three caspase inhibitors, Ac-V AD-cmk (caspase-1 inhibitor), z-DEVD-fmk (caspase -3 inhibitor) and B- D-fmk (BOCDFK, a general inhibitor), for protecting auditory sensory c ells from cisplatin-damage induced loss. Treatment of 3-day-old rat or gan of Corti explants with these caspase inhibitors protected > 80% of the auditory hair cells from cisplatin-damage initiated apoptosis. Di ssociated cell cultures of 3-day-old rat spinal ganglia treated with a ny of these three caspase inhibitors in addition to exogenous neurotro phin have highly significant increases in neuronal survival following cisplatin exposure. These results indicate that loss of auditory senso ry cells as a result of cisplatin-induced damage involves apoptosis an d that blocking of this cell death pathway at the caspase level effect ively rescues both hair cells and neurons. (C) 1998 Rapid Science Ltd.