IN-VITRO AND ANIMAL STUDIES OF SODIUM THIOSULFATE AS A POTENTIAL CHEMOPROTECTANT AGAINST CARBOPLATIN-INDUCED OTOTOXICITY

When carboplatin s-diammine-1,1-cyclobutane-dicarboxylato-platinum) de livery to brain tumors is optimized with osmotic blood-brain barrier d isruption (BBBD), high frequency hearing loss can result. Treatment wi th sodium thiosulfate (STS) blocked carboplatin cytotoxicity against t he LX-I human small cell lung carcinoma cell line in vitro. STS decrea sed carboplatin-induced ototoxicity in a guinea pig model, as determin ed by electrophysiological measurements and analysis of inner ear oute r hair cell numbers. Protection was found when STS was administered up to 8 h subsequent to carboplatin but not 24 h after carboplatin. In a rat model of osmotic BBBD, STS was neurotoxic when given immediately after BBBD but not when given 60 min after BBBD, when the barrier is r eestablished. Thus, delayed administration of STS mag provide a mechan ism to reduce the cochlear toxicity caused by BBBD-enhanced carboplati n delivery to the brain.