Uno Barcelli

Enhancing effect of dietary supplementation with ω-3 fatty acids on plasma fibrinolysis in normal subjects

A supplement of MaxEPA oil containing 5 g of omega-3 polyunsaturated fatty acids was given for two weeks to nine normal volunteers. The vascular plasminogen activator (VPA) level increased and there was a fall in the levels of inhibitors of vascular plasminogen activator (IPA) and of plasmin, alpha 2-antiplasmin (alpha 2-AP). No significant changes occur in serum cholesterol, triglycerides, HDL or LDL levels.

Beneficial effects of polyunsaturated fatty acids in partially nephrectomized rats

Evening primrose oil, safflower oil, and salmon oil, all with high polyunsaturated fatty acid content, were fed to partially nephrectomized rats; the effects were compared to those of feeding beef tallow. All three oils had favorable effects on progression of renal failure, salmon oil on kidney histology as well. The changes induced in platelet production of thromboxane A2, and in the renal production of various eicosanoids may explain the protective role of these oils.

High Linoleic Acid Diets Ameliorate Diabetic Nephropathy in Rats

The value of high polyunsaturated fatty acid (PUFA) diets in preventing diabetic nephropathy in rats was studied. Diabetes was induced by intravenous injection of streptozotocin (SZ), 65 mg/kg. Rats were divided in four groups fed diets containing 11% fat for 38 weeks. Dietary fat derived from four sources: beef tallow (BT; rich in saturated fatty acids), evening primrose oil (EPO; rich in gamma linolenic [GLA] and linoleic acids [LA]), safflower oil (SO; rich in LA), and fish oil (FO; rich in eicosapentaenoic [EPA] and docosahexaenoic [DHA] acids). Ultralente insulin was administered every other day to maintain the blood glucose levels between 11.1 and 22.2 mmol/L (200 and 400 mg/dL). The diets prepared with EPO and SO had a clear beneficial effect on proteinuria, glomerular sclerosis, and tubular abnormalities, as compared with BT. Both diets also increased the ratio of renal cortical production of 6-keto-PGF1 alpha to thromboxane B2 (TXB2), the stable metabolites of PGI2 and TXA2, respectively. They did not induce significant changes in plasma lipid composition. The FO diet did not have an effect on renal disease, but decreased plasma lipids and inhibited eicosanoid synthesis by platelets and kidney cortex. FO feeding was associated with a lowered 6-keto-PGF1 alpha/TXB2 ratio. It is concluded that high LA diets are protective in this model of diabetic nephropathy. The effect may be secondary to modifications of the eicosanoid balance. Diets containing FO have a beneficial effect on plasma lipids in this model.

Fish oil has beneficial effects on lipids and renal disease of nephrotic rats

The effects of fish oil on serum lipids, eicosanoid production, fibrinolysis, and renal disease of nephrotic rats were studied. Three groups of rats were given adriamycin to induce nephrotic syndrome. They were pair-fed diets containing 14% beef fat, 3%, and 14% fish oil, and killed at 4 weeks. Marked beneficial effects of the fish oil on plasma triglycerides, total cholesterol, and LDL cholesterol were observed. Fish oil suppressed dienoic eicosanoid production. Protection of renal function and morphology was achieved in the fish oil fed groups, as evidenced by lower serum creatinine levels and lesser degrees of tubular dilatation and intraluminal protein in the kidney tubules. We conclude that fish oil, rich in n-3 fatty acids, is beneficial to the plasma lipids and may prevent progression of renal disease in this model of nephrotic syndrome. These two events may be interrelated.

The influence of n-6 and n-3 fatty acids on kidney phospholipid composition and on eicosanoid production in aging rats

Changes in eicosanoid production may contribute to some of the complications of the aging process such as atherosclerosis and glomerular sclerosis. Polyunsaturated fatty acids of the n-6 and n-3 series are precursors of eicosanoids. We fed diets containing safflower oil as a source of n-6 fatty acids, fish oil as a source of n-3 fatty acids or beef tallow as a source of saturated fats to three groups of normal rats from 2–18 months of age. We demonstrated incorporation of the n-3 fatty acids, 20:5n-3 and 22:6n-3 into kidney phospholipids. Feeding of the diet containing n-3 fatty acids was associated with a markedly decreased giomerular production of PGE, 6-keto-PGF1α and TXB2. It also decreased the aortic production of 6-keto-PGF1α and platelet production of TXB2. No significant effect of n-6 fatty acids on dienoic eicosanoid production was observed. There were no adverse effects on kidney function as measured by urinary protein excretion and serum creatinine levels or on renal morphology by any diet. A diet enriched in n-3 fatty acids for 18 months remains effective in decreasing dienoic eicosanoids in the aging rat.

A diet containing n-3 and n-6 fatty acids favorably alters the renal phospholipids, eicosanoid synthesis and plasma lipids in nephrotic rats

The nephrotic syndrome was induced in rats by intravenous adriamycin (3 mg/kg). The rats were then divided into four groups which, for six weeks, were pair-fed diets containing beef tallow (BT), fish oil (FO), a source of n−3 fatty acids, evening primrose oil (EPO), a source of n−6 fatty acids, or a combination of evening primrose oil and fish oil, 75∶25 (EPO:FO). The fat content of the diets was 15%. Significant incorporation of the fatty acids into kidney phospholipids was demonstrated. Diets containing FO, EPO and EPO:FO lowered plasma triglycerides and total cholesterol levels as compared with diets containing BT. Only EPO:FO raised high density lipoprotein (HDL) cholesterol levels, as compared with BT. The combination EPO:FO prevented the tenfold suppression of aortic 6-keto-PGF1α caused by FO. These changes in plasma lipids and eicosanoid production are potentially antiatherogenic and may prevent glomerular sclerosis. The combination of EPO and FO, containing n−6 and n−3 fatty acids may offer advantages over either family of fatty acids in this model of nephrotic syndrome.

Dietary fat in experimental nephrotic syndrome: Beneficial effects of fish oil on serum lipids and, indirectly, on the kidney

Three isocaloric diets with different fat composition were fed to rats for seven weeks after the production of nephrotic syndrome by adriamycin. The effects of feeding 3% and 14% fish oil were compared with those of feeding beef fat. At the fourth week of feeding the levels of triglycerides and cholesterol were lower in both fish oil fed groups. At the seventh week these levels, and the LDL cholesterol, were lower only in the 14% fish oil group. In rats fed beef fat, but not in those fed fish oil, there was a striking positive correlation of the four-week serum triglycerides and cholesterol with the seven-week serum creatinine level and with the degree of glomerular hyalinosis and endothelial swelling. The favorable effects of fish oil feeding on serum lipids may have a protective effect on the development of glomerular damage.

Protective effect of polyunsaturated fatty acid supplementation in apoferritin induced murine glomerulonephritis.

The effects of increasing two dietary polyunsaturated fatty acids, eicosapentaenoic and linoleic, on the glomerulonephritis induced by repeated injections of apoferritin in the mouse were studied. Urinary protein excretion was measured serially; serum creatinine, aortic and renal production of eicosanoids and kidney histology were measured at sacrifice at 8 weeks. Both high EPA and LA feedings were associated with lesser proteinuria, normalization of renal function and profound changes in the tissue production of prostaglandin and thromboxane, which may explain their protective effect in this model of renal disease.

Effects of Dietary Linoleic Acid Enrichment on Induction of Immune Complex Nephritis in Mice

In pharmacologic doses E series prostaglandins attenuate the development of immune complex nephritis. We studied the effect of the dietary prostaglandin precursor linoleic acid on murine apoferritin-induced immune complex glomerulonephritis. High, normal, or low linoleic acid diets were fed to mice for 4 weeks prior to and during the intraperitoneal apoferritin administration. A high linoleic acid diet feeding was associated with less proteinuria, less renal histologic damage, and prevented a rise in serum creatinine. We conclude that linoleic acid has a protective effect on the development of murine apoferritin-induced immune complex nephritis.

Measurement of prostaglandin E3 and other eicosanoids in biologic samples using high pressure liquid chromatography and radioimmunoassay.

A method to measure PGE3 in biologic samples is described. Complete resolution of PGE3 from PGE1 and PGE2 is achieved by reversephase high pressure liquid chromatography. Quantification is carried out by radioimmunoassay using an antibody directed against PGE2 that has high cross-reactivity with PGE3. Using this method, a marked increase in PGE3 production by mouse kidney tissue and in rat urine was demonstrated after supplemental feeding of omega-3 fatty acids. This method can also be applied to measurement of 6-keto-PGF1 alpha and TXB2 in the same samples.