Neurotoxicity of quelamycin in the rat

Male Sprague-Dawley rats were given a single dose of 10 or 20 mg/kg quelamycin intravenously and perfusion fixed at 4, 12, 28 and 48 days after drug administration. Light microscopical study of 1 micrometer thick sections of dorsal root ganglia revealed focal regions of neuronal nuclear clearing involving 40-50% of neurons at 4 days. There was subsequent progressive reduction in the incidence of such lesions. Neuronal necrosis apparently affecting less than one percent of dorsal root ganglia neurons was noted initially at 12 days in the 20 mg/kg group and 28 days in the 10 mg/kg group. Comparison of these findings with previous studies indicated that quelamycin was less neurotoxic to rats than its parent compound adriamycin.