Release of iron from ferritin by metabolites of benzene and superoxide radical generating agents

Abstract

The release of iron from ferritin in the presence of benzene metabolites, viz. phenol (P), catechol (CT), hydroquinone (HQ) and superoxide radical generating compounds, viz. pyrogallol (PL), phloroglucinol (PG), phenylhydrazine (PH) or phenylenediamine (PD) was studied in acetate buffer, pH 5.6. Monitoring the formation of the iron–ferrozine complex quantitated the release of iron from ferritin. The presence of P (125 μM) did not result in the release of iron from ferritin, whereas the same concentration of CT, HQ, PL, PH or PD resulted in the release of significant amounts of iron from ferritin and a marginal amount of iron in the presence of PG, CT, HQ, PL, PH or PD concentration and time-dependent increase in iron release from ferritin were observed although the increase was not linear as a function of time and concentration of the compounds studied. The presence of superoxide dismutase inhibited significantly the release of iron from ferritin by CT, HQ, PL, PH or PD. The iron released from ferritin by CT, HQ, PL, PH or PD enhanced lipid peroxidation in rat brain homogenate and released aldehydic products from bleomycin-dependent degradation of DNA and also caused single strand nicks to pUC18 DNA. These studies indicate that CT and HQ, the two principal polyphenolic metabolites of benzene and PL, PH or PD, the superoxide radical generating compounds were capable of reducing ferric iron from ferritin and also mobilizing and releasing iron from ferritin core. The release of iron from ferritin by these compounds is a result of direct reduction of ferritin iron by electron transfer and also reduction via superoxide radical. The release of iron from ferritin by CT and HQ may have toxicological implications in relation to benzene toxicity. The release of iron by superoxide radical generating agents suggests that oxidative stress may play a role as this could lead to disruption of intracellular iron homeostasis.