Luciano Saso, Giovanni Valentini, Maria Luisa Casini, Eleonora Mattei,
Laura Braghiroli, Gabriela Mazzanti, Claudio Panzironi, Eleonora Grippa
and Bruno Silvestrini (*)
Institute of Pharmacology and Pharmacognosy,University "La Sapienza",
P.Ie AIdo Moro 5, 00185 Rome, Italy
(*) To whom correspondence should be addressed.
Abstract: 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.
Keywords: Antidenaturant agent, Anti-rheumatic agent, Albumin, Fish oil,
n-3-Polyunsaturated fatty acid