Stabilization of rat serum proteins following oral administration of fish oil

The mechanism of action of fish oil (FO), currently used in different chron ic inflammatory conditions such as rheumatoid arthritis (RA), is not comple tely understood, although it is thought that it could alter the metabolism of endogenous autacoids. In addition, we hypothesized that the known capabi lity of fatty acids (FA) of stabilizing serum albumin and perhaps other pro teins, may be of pharmacological relevance considering that it is shared by other anti-rheumatic agents (e.g. nonsteroidal antiinflammatory drugs). Th us, 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 pr otein denaturation. FO, and, to a lower extent, CO inhibited heat-induced d enaturation of rat serum (RS): based on the inhibitory activity (EC50) of t he major fatty acids against heat-induced denaturation of RS in vitro, it w as 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 l inolenic 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 af finity chromatography technique, obtaining high purity rat serum albumin pr eparations (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 m in, 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 b ound long chain fatty acids (e.g. palmitic acid and EPA). We speculate that the stabilization of serum albumin and perhaps other proteins could preven t changes of antigenicity due to protein denaturation and glycosylation, wh ich may trigger pathological autoimmune responses, suggesting that this act ion may be involved in the mode of action of FO in RA and other chronic inf lammatory diseases.