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

The release of iron from ferritin in the presence of benzene metabolites, v iz, phenol (P), catechol (CT), hydroquinone (HQ) and superoxide radical gen erating compounds, viz. pyrogallol (PL), phloroglucinol (PG), phenylhydrazi ne (PH) or phenylenediamine (PD) was studied in acetate buffer, pH 5.6. Mon itoring the formation of the iron-ferrozine complex quantitated the release of iron from ferritin. The presence of P (125 muM) did not result in the r elease 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 ferri tin and a marginal amount of iron in the presence of PG, CT, HQ, PL, PH or PD concentration and tithe-dependent increase in iron release from ferritin were observed although the increase was not linear as a function of time a nd concentration of the compounds studied. The presence of superoxide dismu tase inhibited significantly the release of iron from ferritin by CT, HQ, P L, PH or PD. The iron released from ferritin by CT, HQ, PL, PH or PD enhanc ed lipid peroxidation in rat brain homogenate and released aldehydic produc ts from bleomycin-dependent degradation of DNA and also caused single stran d nicks to pUC18 DNA. These studies indicate that CT and HQ, the two princi pal polyphenolic metabolites of benzene and PL, PH or PD, the superoxide ra dical generating compounds were capable of reducing ferric iron from ferrit in and also mobilizing and releasing iron from ferritin core. The release o f iron from ferritin by these compounds is a result of direct reduction of ferritin iron by electron transfer and also reduction via superoxide radica l. The release of iron from ferritin by CT and HQ may have toxicological im plications in relation to benzene toxicity. The release of iron by superoxi de radical generating agents suggests that oxidative stress may play a role as this could lead to disruption of intracellular iron homeostasis. (C) 20 01 Elsevier Science Ireland Ltd. All rights reserved.