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Molecular aspects of catechol and pyrogallol inhibition of liver microsomal lipid peroxidation stimulated by ferrous ion-ADP-complexes or by carbon tetrachloride

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Summary

Lipid peroxidation was induced in rat liver microsomes either by iron-ADP-complexes or by carbon tetrachloride in the presence of NADPH. Different compounds containing catechol or pyrogallol structures were examined for their activities to inhibit lipid peroxidation in both systems. In general, all compounds tested showed similar inhibitory activities on lipid peroxidation, if induced by ferrous ion-ADP-complexes or by carbon tetrachloride. This inhibition is explained by the suggestion that catechols and pyrogallos inhibit at the lipid site of the membrane, rather than at the enzymic site. Compounds not containing catechol or pyrogallol groups inhibited lipid peroxidation only weakly. O-Methylation resulted in a decrease of the inhibitory effect. Catecholor pyrogallol-derivatives which contained polar functional side chains, like carboxyl- or amino groups showed minor inhibitory effects compared to the esterified or N-alkylated compounds.

Dihydroxychlorpromazine, 2-hydroxy-estradiol and 2-hydroxyethinylestradiol were the most effective inhbitors of microsomal lipid peroxidation (I50-values of 1×10−6 to 2×10−7 M). The inhibitory activity of α-tocopherol, glutathione and ascorbic acid, naturally occurring antioxidants, was about three orders of magnitude lower.

Inhibition of lipid peroxidation induced by NADPH-cytochrome c reductase and iron-ADP-complexes in the presence of NADPH and liposomes was also observed with catechols.

From our results we assume that the molecular structure of a catechol or pyrogallol functional group is a prequisite for an effective inhibition of lipid peroxidation by these chemicals. Furthermore, the results are discussed in relation to the requisite membrane affinity of catechols, pyrogallols and other antioxidants which might be used for inhibition studies on lipid peroxidation in vivo.

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  1. Institut für Toxikologie der Universität Tübingen, Wilhelmstrasse 56, D-7400, Tübingen, Federal Republic of Germany

    H. Kappus, H. Kieczka, M. Scheulen & H. Remmer

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  1. H. Kappus
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  2. H. Kieczka
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  3. M. Scheulen
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  4. H. Remmer
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Kappus, H., Kieczka, H., Scheulen, M. et al. Molecular aspects of catechol and pyrogallol inhibition of liver microsomal lipid peroxidation stimulated by ferrous ion-ADP-complexes or by carbon tetrachloride. Naunyn-Schmiedeberg's Arch. Pharmacol. 300, 179–187 (1977). https://doi.org/10.1007/BF00505049

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