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

Natural hydrophobic substances like bile salts (cholate, deoxycholate, chen odeoxycholate, lithocholate and their conjugates with glycine and taurine), fatty acids (caprylic, capric, lauric, myristic, palmitic, stearic, oleic, linoleic, arachidonic, eicosapentaenoic and docosahexaenoic acid) were muc h more active (EC(50)congruent to 10(-4)-10(-5) M) than selected amino acid s (EC50 > 10(-2) M) and inorganic salts (EC(50)congruent to 10(-1) M) in in hibiting heat-induced denaturation of human serum albumin in vitro. Fish oi l, rich in n-3-polyunsaturated acids such as eicosapentaenoic acid and doco sahexaenoic 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 act ivity of fish oil may be partly tin addition to the known effect on endogen ous eicosanoid composition) responsible for its beneficial effects in rheum atoid arthritis and other rheumatic conditions. In this connection, it is o f note that the in vitro antidenaturant activity of fish oil fatty acids wa s higher than that of known antidenaturant drugs such as bendazac and binda rit and nonsteroidal anti-inflammatory drugs like phenylbutazone and indome thacin which could exert beneficial effects in chronic inflammatory conditi ons by stabilizing endogenous proteins.