Inhibition of Protein Denaturation by Fatty Acids, Bile Salts and Other Natural Substances: A New Hypothesis for the Mechanism of Action of Fish Oil in Rheumatic Diseases.

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  • Saso Luciano
    Institute of Pharmacology and Pharmacognosy, University “La Sapienza”
  • Valentini Giovanni
    Institute of Pharmacology and Pharmacognosy, University “La Sapienza”
  • Casini Maria Luisa
    Institute of Pharmacology and Pharmacognosy, University “La Sapienza”
  • Mattei Eleonora
    Institute of Pharmacology and Pharmacognosy, University “La Sapienza”
  • Braghiroli Laura
    Institute of Pharmacology and Pharmacognosy, University “La Sapienza”
  • Mazzanti Gabriela
    Institute of Pharmacology and Pharmacognosy, University “La Sapienza”
  • Panzironi Claudio
    Institute of Pharmacology and Pharmacognosy, University “La Sapienza”
  • Grippa Eleonora
    Institute of Pharmacology and Pharmacognosy, University “La Sapienza”
  • Silvestrini Bruno
    Institute of Pharmacology and Pharmacognosy, University “La Sapienza”

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タイトル別名
  • Inhibition of Protein Denaturation by Fatty Acids Bile Salts and Other Natural

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Natural hydrophobic substances like bile salts (cholate, deoxycholate, chenodeoxycholate, lithocholate and their conjugates with glycine and taurine), fatty acids (caprylic, capric, lauric, myristic, palmitic, stearic, oleic, linoleic, arachidonic, eicosapentaenoic and docosahexaenoic acid) were much more active (EC50≅10-4 - 10-5 M) than selected amino acids (EC50 >10-2 M) and inorganic salts (EC50≅10-1 M) in inhibiting heat-induced denaturation of human serum albumin in vitro. Fish oil, rich in n-3-polyunsaturated acids such as eicosapentaenoic acid and docosahexaenoic acid, administered p.o. (1 ml/kg) in the rat, protected ex vivo (after 2 hr) serum against heat-induced denaturation more than bendazac, a known antidenaturant drug. Thus, we speculated that the antidenaturant activity of fish oil may be partly (in addition to the known effect on endogenous eicosanoid composition) responsible for its beneficial effects in rheumatoid arthritis and other rheumatic conditions. In this connection, it is of note that the in vitro antidenaturant activity of fish oil fatty acids was higher than that of known antidenaturant drugs such as bendazac and bindarit and nonsteroidal anti-inflammatory drugs like phenylbutazone and indomethacin which could exert beneficial effects in chronic inflammatory conditions by stabilizing endogenous proteins.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 79 (1), 89-99, 1999

    公益社団法人 日本薬理学会

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