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A ferriprotoporphyrin IX-chloroquine complex promotes membrane phospholipid peroxidation. A possible mechanism for

Y Sugioka1, M Suzuki, K Sugioka

  • 1Department of Parasitology, Gunma University School of Medicine, Maebashi, Japan.

FEBS Letters
|November 2, 1987
PubMed

Insights

The ferriprotoporphyrin IX-chloroquine complex significantly enhances lipid peroxidation in phospholipid membranes. DL-alpha-Tocopherol effectively inhibited this iron-induced process, suggesting a protective role.

Area of Science:

  • Biochemistry
  • Membrane Biology
  • Oxidative Stress

Background:

  • Lipid peroxidation is a key process in oxidative stress.
  • Ferriprotoporphyrin IX is a heme derivative with potential pro-oxidant activity.
  • Chloroquine is an antimalarial drug whose interactions with cellular components are of interest.

Purpose of the Study:

  • To investigate the effect of a ferriprotoporphyrin IX-chloroquine complex on phospholipid membranes.
  • To determine the role of iron-induced lipid peroxidation in this interaction.
  • To assess the potential inhibitory effect of DL-alpha-Tocopherol.

Main Methods:

  • Microsomal phospholipid liposomes were used as a model membrane system.
  • Lipid peroxidation was induced by iron and assessed in the presence of the ferriprotoporphyrin IX-chloroquine complex.
  • The effect of ferriprotoporphyrin IX alone, protoporphyrin IX with chloroquine, and Fe3+-ADP with chloroquine was also evaluated.
  • DL-alpha-Tocopherol was used to test for inhibition of lipid peroxidation.

Main Results:

  • The ferriprotoporphyrin IX-chloroquine complex significantly promoted peroxidative cleavage of unsaturated phospholipids in liposomes.
  • Ferriprotoporphyrin IX alone showed less promotion of lipid peroxidation compared to the complex.
  • Neither protoporphyrin IX with chloroquine nor Fe3+-ADP with chloroquine promoted significant lipid peroxidation.
  • DL-alpha-Tocopherol completely inhibited the lipid peroxidation induced by the ferriprotoporphyrin IX-chloroquine complex.

Conclusions:

  • The ferriprotoporphyrin IX-chloroquine complex acts as a potent inducer of lipid peroxidation in phospholipid membranes.
  • This effect appears to be specific to the ferriprotoporphyrin IX-chloroquine combination and iron-induced mechanisms.
  • DL-alpha-Tocopherol demonstrates a complete inhibitory effect, highlighting its antioxidant potential against this specific pro-oxidant complex.

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