THE EFFECT OF THE NEUROBLASTOMA-SEEKING AGENT METAIODOBENZYLGUANIDINE(MIBG) ON NADH-DRIVEN SUPEROXIDE FORMATION AND NADH DRIVEN LIPID-PEROXIDATION IN BEEF-HEART SUBMITOCHONDRIAL PARTICLES

In this paper we report the effects of the neuroblastoma-seeking agent meta-iodobenzylguanidine (MIBG) on NADH-driven superoxide formation a nd NADH-driven lipid peroxidation in beef heart submitochondrial parti cles. MIBG is a structural analogue of noradrenaline and is capable of inhibiting complex I and complex III of the respiratory chain. The re sults of our studies show that MIBG enhanced both NADH-driven superoxi de formation and NADH-driven Lipid peroxidation at concentrations that are likely to exist inside mitochondria of the target cells of neurob lastoma patients treated with [I-131]MIBG. The effect of MIBG is compa rable to that of rotenone (an inhibitor of complex I) rather than that of antimycin (an inhibitor of complex III). These results suggest tha t the formation of superoxide and lipid peroxidation contributes to th e cytotoxicity of [I-131]MIBG. (C) 1997 Elsevier Science Ltd.