Cytotoxic properties of iron-hydroxynaphthoquinone complexes in rat hepatocytes.

The mechanisms of toxicity to isolated rat hepatocytes of Fe(II) and Fe(III) complexes of two structurally related naphthoquinones have been studied. All complexes were found to show a dose-dependent toxicity which precedes cell death. Within the naphthoquinone series the order of toxicity is Fe(II) > parent naphthoquinone > Fe(III). The iron complexes of 5-OH-1,4 naphthoquinone (5-OH-1,4 NQ; Juglone) are more toxic than the iron complexes of 2-OH-1,4 naphthoquinone (2-OH-1,4 NQ; Lawsone) indicating that the mechanisms of toxicity are different. Electrochemical studies on these complexes shows that 5-OH-1,4 NQ facilitates formation of stable semiquinone species while 2-OH-1,4 NQ does not. The low redox potential of 2-OH-1,4 NQ makes it a poor substrate for metabolism by reductases.