Effects of deferrioxamine on iron-catalyzed lipid peroxidation

Miller, Dennis M.; Spear, Nathan; Aust, Steven D.

doi:10.1016/0003-9861(92)90513-v

Cited by 34 publications

(16 citation statements)

References 27 publications

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“…Indeed in our experiments both low (10 mg/kg per day) and high (150 mg/kg per day) doses of DEF aggravated the condition of mice infected with influenza virus. The prooxidant properties of DEF have been reported by others (13)(14)(15)(16). In vitro studies have shown that in the presence of O 2 and Fe(II), DEF is a prooxidant (17).…”

supporting

confidence: 62%

Application of various antioxidants in the treatment of influenza

Dolganova

Sharonov

1997

Braz J Med Biol Res

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We determined the effect of the antioxidants superoxide dismutase, desferrioxamine and allopurinol on the survival of male CBA mice infected intranasally with 2-5 LD 50 lung influenza virus A/Aichi/2/68. Survival for at least 20 days was observed for 45% of the mice that received 1000 U/day superoxide dismutase prepared from red blood cells on days 5, 6, 7 and 8 after infection, and 75% survival was observed for mice that received the same dose on days 4, 5, 6, 7 and 8. Desferrioxamine, 25 mg/kg per day and 100 mg/kg per day injected subcutaneously, resulted in survival rates of 5 and 0%, respectively, compared to 10% survival observed for saline-injected controls. Allopurinol at doses of 5 to 50 mg/kg per day had no effect on mouse survival. These data demonstrate the efficacy of superoxide dismutase for the protection of mice against hemorrhagic lung edema. The ineffectiveness of allopurinol suggests that the xanthine oxidase system does not play a major role in hemorrhage or lung edema and that caution is necessary when desferrioxamine is administered during an acute inflammatory process accompanied by erythrocyte lysis.

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supporting

confidence: 62%

Application of various antioxidants in the treatment of influenza

Dolganova

Sharonov

1997

Braz J Med Biol Res

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“…Membrane damage, another symptom of oxidative stress, may also result when iron is leached from these clusters. While some of the spilled iron deposits on the polyanionic nucleic acids and causes damage to them, other iron may collect along the negatively charged lipid bilayer, where workers have anticipated that it could promote lipid peroxidation (61). This connection remains to be tested.…”

Section: Discussionmentioning

confidence: 99%

Superoxide accelerates DNA damage by elevating free-iron levels

Keyer

Imlay²

1996

Proc. Natl. Acad. Sci. U.S.A.

768

660

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Superoxide promotes hydroxyl-radical formation and consequent DNA damage in cells of all types. The long-standing hypothesis that it primarily does so by delivering electrons to adventitious iron on DNA was refuted by recent studies in Escherichia coli. Alternative proposals have suggested that superoxide may accelerate oxidative DNA damage by leaching iron from storage proteins or enzymic [4Fe-4S] clusters. The released iron might then deposit on the surface of the DNA, where it could catalyze the formation of DNA oxidants using other electron donors. The latter model is affirmed by the experiments described here. Whole-cell electron paramagnetic resonance demonstrated that the level of loose iron in superoxide-stressed cells greatly exceeds that of unstressed cells. Bacterial iron storage proteins were not the major source for free iron, since superoxide also increased iron levels in mutants lacking these iron storage proteins. However, overproduction of an enzyme containing a labile [4Fe-4S] cluster dramatically increased the free iron content of cells when they were growing in air. The rates of spontaneous mutagenesis and DNA damage from exogenous H 2 O 2 increased commensurately. It is striking that both growth defects and DNA damage caused by superoxide ensue from its ability to damage a subset of iron-sulfur clusters.

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“…This finding may be due to bound metals leaching from ceruloplasmin and redox cycling and may explain the experimental results observed in Figure 3 and discussed below. Nevertheless, preincubation of epinephrine with Desferal for 72 hours was necessary for 100% inhibition of epinephrine oxidation, which is not surprising given that Desferal cannot bind iron immediately from other iron chelates (16) and that the affinity of Desferal for copper is less than that for iron (23,24).…”

Section: Discussionmentioning

confidence: 99%

The role of metals in the enzymatic and nonenzymatic oxidation of epinephrine

Ryan

Miller

Aust

1993

J. Biochem. Toxicol.

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The effects of transition metals on nonenzymatic and ceruloplasmin catalyzed epinephrine oxidation were investigated by studying rates of epinephrine oxidation in purified buffers and in the presence of metal chelating agents. We found that epinephrine does not "autoxidize" in sodium chloride solutions prepared with deionized water that was further purified by chromatography over Chelex 100 resin prior to use. Epinephrine was oxidized rapidly in sodium chloride prepared with tap water (1.20 +/- 0.12 nmoles/min) or in deionized water (0.40 +/- 0.80 nmoles/min), but this oxidation was prevented by the addition of Desferal, a potent metal chelating agent. Epinephrine oxidation was enhanced upon the addition of ceruloplasmin, and this oxidation rate could be slowed, but not eliminated, by the addition of Desferal. If epinephrine solutions were preincubated for 72 hours with Desferal prior to ceruloplasmin addition, however, no oxidation was observed. Epinephrine was shown to form colored complexes with both iron and copper at pH 7.0. The Fe(III)-epinephrine complex was much more stable than was the Cu(II)-epinephrine complex. Oxygen consumption studies of ceruloplasmin catalyzed epinephrine oxidation showed that copper was a better promoter of epinephrine oxidation than was iron, suggesting that ceruloplasmin-catalyzed epinephrine oxidation results from adventitious copper bound to the purified enzyme. In light of these results, the physiological relevance of ceruloplasmin catalyzed oxidation of biogenic amines may be minor.

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Effects of deferrioxamine on iron-catalyzed lipid peroxidation

Cited by 34 publications

References 27 publications

Application of various antioxidants in the treatment of influenza

Application of various antioxidants in the treatment of influenza

Superoxide accelerates DNA damage by elevating free-iron levels

The role of metals in the enzymatic and nonenzymatic oxidation of epinephrine

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