Some aspects of porphyrin neurotoxicity in vitro

Abstract

Using a dissociated primary sensory neuron culture system, it is observed that some naturally occurring porphyrins produce dose-dependent neurotoxicity as measured by neuron death and by inhibition of the neurite outgrowth induced by Nerve Growth Factor (NGF). However, the porphyrin precursor δ-aminolcvulinic acid (δ-ALA) is not toxic up to millimolar concentrations within a 30-h time period. Two synthetic porphyrins, tetraphenylporphine sulfonate (TPPS) and hematoporphyrin derivative (HPD), have also been shown to be toxic in vitro.Cultures and cocultures of isolated populations of neurons and glia of central and peripheral nervous system origin may prove advantageous in the study of porphyrin influences on the intact nervous system. This in vitro assay system can complement in vivo paradigms and may be useful for rapid quantitative screening for neurotoxicity of radiation sensitizers including the synthetic porphyrins and other chemotherapeutic agents.