We studied the effects of fish oil on the progression of renal insufficiency in rats with subtotal nephrectomy. Five weeks after a 1-2/3 nephrectomy, sixteen rats were fed two different diets which differed only in fat composition. Lipid in the control diet was primarily beef tallow; that of the experimental diet, menhaden oil. Fish oil-fed rats had significant increases in plasma creatinines, decreases in urinary PGE2 and accelerated death rates. An additional twelve rats underwent 1-1/3 nephrectomies, and the same dietary manipulations, followed by renal clearance, histologic and biochemical studies after 12 weeks on the diets. Fish oil-fed rats again did worse, with decreased glomerular filtration rates and filtration fractions, more proteinuria and more glomerular sclerosis. Glomeruli and slices of cortex, medulla and papillae from rats fed fish oil produced much less PGE2 and TXB2 than dietary controls. Fish oil-induced suppression of renal PGE2 may be deleterious in this model and may outweigh the beneficial effect derived from TXA2 suppression. In contrast to fish oil's potentially therapeutic role in cardiovascular and immune-mediated renal disease, this diet is detrimental in rat renoprival nephropathy. This illustrates the importance of examining the effects of fatty acid manipulation individually for each disease entity.

In chronic rheumatoid arthritis, the synovial membrane grows as a pannus over the articular cartilage and erodes it, producing irreversible changes in joint structure and function. On the basis of many experimental observations, hydrolytic enzymes from various sources in the rheumatoid joint have been thought to contribute to the dissolution of the cartilage matrix.Barnett (1) showed that when hyaluronidase was injected into a rabbit joint which was then vigorously exercised, there was a loss of articular cartilage ground substance, presumably due to digestion of the polysaccharide chains of the protein-polysaccharide (PP) of the matrix. Since Dingle (2) first proposed that lysosomal enzymes might degrade the matrix of articular cartilage in the rheumatoid joint, considerable indirect evidence has accumulated to support this suggestion. Some of the evidence and literature citations are presented elsewhere (3, 4) and are briefly summarized here. The rheumatoid synovial membrane contains a much higher content of lysosomal enzymes than the normal membrane, as revealed by cytochemical stains using the light and electron microscope, and by chemical analyses of enzyme activities in homogenates. High levels of lysosomal enzymes are present in rheumatoid synovial fluids and presumably arise either from dissolution of leukocytes in the fluid, or from lining cells in the synovial membrane, or from both. Extracts of rheumatoid, but not normal, synovial membrane and preparations of lysosomal enzymes obtained from liver degrade viscous solutions of the ground substance extracted from cartilage matrix. Injection into rabbit joints of streptolysin S, which is thought to "labilize" lysosomal enzymes, causes a proliferative synovitis with pannus formation and cartilage erosion.The experimental basis for reversible cartilage matrix depletion by proteolytic enzymes was provided by Thomas (5). He showed that papain injected intravenously into rabbits caused their ears to droop. After several days, the ears returned to their erect position.

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