title: Stabilization of rat serum proteins following oral administration of fish oil.
abstract: The mechanism of action of fish oil (FO), currently used in different chronic inflammatory conditions such as rheumatoid arthritis (RA), is not completely understood, although it is thought that it could alter the metabolism of endogenous autacoids. In addition, we hypothesized that the known capability of fatty acids (FA) of stabilizing serum albumin and perhaps other proteins, may be of pharmacological relevance considering that it is shared by other anti-rheumatic agents (e.g. nonsteroidal antiinflammatory drugs). Thus, we studied the effect of oral administration of FO and corn oil (CO), a vegetable oil with a different composition, on the stability of rat serum proteins, evaluated by a classical in vitro method based on heat-induced protein denaturation. FO, and, to a lower extent, CO inhibited heat-induced denaturation of rat serum (RS): based on the inhibitory activity (EC50) of the major fatty acids against heat-induced denaturation of RS in vitro, it was possible to speculate that in vivo effects of palmitic acid (C16:0) and eicosapentaenoic acid (EPA, C20:5, n-3) may be more relevant than that of linolenic acid (C18:2). To better investigate this phenomenon, we extracted albumin from the serum of animals treated or not with FO with a one-step affinity chromatography technique, obtaining high purity rat serum albumin preparations (RSA-CTRL and RSA-FO), as judged by SDS-PAGE with Coomassie blue staining. When these RSA preparations were heated at 70 degrees C for 30 min, it was noted that RSA-FO was much more stable than RSA-CTRL, presumably due to higher number of long chain fatty acids (FA) such as palmitic acid or EPA. In conclusion, we provided evidences that oral administration of FO in the rat stabilizes serum albumin, due to an increase in the number of protein bound long chain fatty acids (e.g. palmitic acid and EPA). We speculate that the stabilization of serum albumin and perhaps other proteins could prevent changes of antigenicity due to protein denaturation and glycosylation, which may trigger pathological autoimmune responses, suggesting that this action may be involved in the mode of action of FO in RA and other chronic inflammatory diseases.
authors.affiliation: Department of Pharmacology of Natural Substances and General Physiology, University of Rome La Sapienza, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Saso
authors.forename: G
authors.initials: G
authors.lastname: Valentini
authors.forename: E
authors.initials: E
authors.lastname: Mattei
authors.forename: C
authors.initials: C
authors.lastname: Panzironi
authors.forename: M L
authors.initials: ML
authors.lastname: Casini
authors.forename: E
authors.initials: E
authors.lastname: Grippa
authors.forename: B
authors.initials: B
authors.lastname: Silvestrini
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D002846:Chromatography, Affinity; D003314:Corn Oil / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005395:Fish Oils / Q000737:chemistry / Q000494:pharmacology*; D006361:Heating; D006801:Humans; D066298:In Vitro Techniques; D011489:Protein Denaturation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D005395:Fish Oils; D012709:Serum Albumin; D003314:Corn Oil; D015118:Eicosapentaenoic Acid