The effect of the neuroblastoma-seeking agent meta-iodobenzylguanidine (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 and NADH-driven lipid peroxidation in beef heart submitochondrial particles. MIBG is a structural analogue of noradrenaline and is capable of inhibiting complex I and complex III of the respiratory chain. The results of our studies show that MIBG enhanced both NADH-driven superoxide formation and NADH-driven lipid peroxidation at concentrations that are likely to exist inside mitochondria of the target cells of neuroblastoma patients treated with [131I]MIBG. The effect of MIBG is comparable to that of rotenone (an inhibitor of complex I) rather than that of antimycin (an inhibitor of complex III). These results suggest that the formation of superoxide and lipid peroxidation contributes to the cytotoxicity of [131I]MIBG.
Cornelissen
J
J
Academic Medical Centre, Department of Pediatrics, Amsterdam, The Netherlands.
Van Kuilenburg
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Voûte
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Van Gennip
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D019797:3-Iodobenzylguanidine; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects; D007462:Iodobenzenes / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009243:NAD / Q000502:physiology; D013367:Submitochondrial Particles / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D000970:Antineoplastic Agents; D007462:Iodobenzenes; D009243:NAD; D013481:Superoxides; D019797:3-Iodobenzylguanidine