Effects of dietary fatty acids in an animal model of focal glomerulosclerosis

The obese Zucker rat develops hyperlipidemia, proteinuria and focal glomerulosclerosis without prior changes in renal hemodynamics. To study the effects of oral fatty acid intake on the development of renal injury in this model, rats were fed standard chow or chow supplemented with either 14% fish oil or 14% beef tallow after unilateral nephrectomy at the age of 10 weeks. At 32 weeks post-nephrectomy animals were sacrificed and renal tissue saved to assess histology and glomerular eicosanoid production. Fish-oil treated rats had lower mean plasma cholesterol levels and developed less proteinuria than control or tallow-fed animals although there was no difference in plasma creatinine or blood pressure. Histological analysis showed significantly fewer sclerosed glomeruli in the fish oil group (4.0 +/- 0.8% vs. control 19.4 +/- 4.1%, P less than 0.0005 and vs. beef tallow 10.8 +/- 1.9%, P less than 0.005). Glomeruli derived from rats on fish oil supplements produced smaller amounts of prostaglandin (PG)E2 and of the stable metabolites of PGI2 (6-oxo-PGF1 alpha), PGF2 (PGF2 alpha) and thromboxane (TX)A2 (TXB2) than those from tallow-fed animals. This study demonstrates that oral fatty acid intake may influence the development of glomerulosclerosis. The apparent beneficial effects of fish oil have not been fully defined, but may relate to favorable changes in plasma lipid concentration and renal eicosanoid production.     

Impact of dietary fatty acid supplementation on renal injury in obese Zucker rats

We previously reported that renal injury in hyperlipidemic, obese Zucker rats was associated with a relative deficiency of tissue polyunsaturated fatty acids (PUFA). In the present study 10-week-old obese Zucker rats were pair fed regular chow or chow containing either 20% sunflower oil rich in n-6 PUFA, fish oil rich in n-3 PUFA, coconut oil medium-chain saturated fatty acid, or beef tallow long-chain saturated fatty acid. At 34 weeks of age there were comparable reductions in albuminuria, mesangial matrix expansion, and glomerulosclerosis in the fish oil and sunflower oil groups. While both fish oil and sunflower oil reduced serum triglycerides, and improved the composition of triglyceride-enriched lipoproteins, only fish oil decreased serum cholesterol. The effect of the dietary fatty acid supplementation on fatty acid profiles were similar in isolated glomeruli and cortical tissue. In general, the amelioration in injury in the fish oil and sunflower oil fed rats was most closely linked to glomerular levels of PUFA, either n-6 or n-3. These data suggest that hyperlipidemia and abnormalities in tissue FA are closely linked, and that dietary supplementation with PUFA may ameliorate chronic, progressive renal injury.     

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.     

Effect of essential fatty acid deficiency on the fatty acid composition and arachidonic acid levels in rat maxillae and mandibles

The fatty acid composition of total lipids and total phospholipids of maxillae and mandibles of rats fed an essential fatty acid-deficient (EFAD), marginally FAD (MEFAD), and a control diet was determined. Patterns typical of an EFA deficiency such as a decrease in the levels of linoleic acid and archidonic acid along with concomitant increase in the levels of palmitoleic acid, oleic acid, and 5,8,11-eicosatrienoic acid were observed in the EFAD groups. Concentrations of arachidonic acid were significantly lower in total lipids of mandibles and maxillae of rats in the EFAD, but not in the MEFAD rats, than those of the controls.     

Altered biliary prostaglandins and cholesterol gallstones: an in vivo study

Recent investigations suggest that biliary prostaglandin metabolism is altered during cholesterol gallstone formation. Most of the available data, however, has been obtained from in vitro studies. The purpose of the present study was to define the effects of cholesterol gallstone formation on in vivo biliary prostaglandin metabolism. Male prairie dogs were fed either a control chow for 21 days or a 1.2% cholesterol-enriched chow for 14-21 days. Cholecystectomy was performed and gallbladder tissue and bile were collected for analysis of prostaglandin concentrations using radioimmunoassay techniques. Gallbladder bile was examined for the presence of crystals and stones. No control animals but all cholesterol-fed animals developed either cholesterol crystals or gallstones (P less than 0.001). Concentrations of prostaglandin E2, prostaglandin F2 (PGF2 alpha), and the stable metabolic products of prostacyclin and thromboxane A2, 6-keto-PGF1 alpha and thromboxane B2 (TXB2), respectively, were decreased 60-85% in the gallbladder tissue of animals with crystals and gallstones compared to controls. Additionally, gallstone containing animals and those with crystals demonstrated a significant increase in the gallbladder bile concentrations of PGF2 alpha, 6-keto-PGF1 alpha, and TXB2. These findings lend support to previously reported in vitro studies suggesting that prostaglandin synthesis increases at an early stage of experimentally induced cholesterol gallstone formation.     

Improved survival of heterotopic cardiac allografts in rats with dietary n-3 polyunsaturated fatty acids

A heterotopic cardiac transplant model, with male Fischer 344 rats as donors and Long Evans rats as recipients, was utilized to investigate the effect of dietary n-3 polyunsaturated fatty acids on acute rejection. Both donor and recipient rats were fed purified diets high in either n-3 polyunsaturated fatty acids (from concentrated n-3 ethyl esters [EE] or fish oil [FO]) or n-6 polyunsaturated fatty acids (from corn oil [CO]) for either 2-3 or 3-4 weeks before transplant. The recipient rats continued on their diets until rejection. The AIN-76A-based diets (with 30% of calories as fat) had adequate essential fatty acids and were balanced for sterols and antioxidants. Allograft survival was significantly increased by 45% when recipient rats were fed EE as compared to the control (CO diet fed to both donor and recipient), regardless of the diet fed to the donor. There was a slight but significant increase in allograft survival when only donor rats were fed the EE diet 2-3 weeks before transplant. With the FO diet (containing one third of the n-3 fatty acids in the EE diet), only the group fed FO to both donor and recipient (starting 2-3 weeks before transplant) showed a significant increase in allograft survival over the control. However, if the FO diets were fed for 3-4 weeks before transplant, increased survival was seen in groups fed FO to either the donor or recipient alone. In this case, allograft survival with FO feeding to both donor and recipient was not different from recipient treatment alone. In all the studies there was a significant and direct correlation between allograft survival and the donor heart phospholipid n-3/n-6 fatty acid ratio and the n-3 fatty acid content (at rejection). There was an indirect relationship with the n-6 fatty acid content. There was no detectable 20:3 (n-9) in the cardiac phospholipids, indicating the absence of essential fatty acid deficiency. Recipient diets were the strongest determinant of the fatty acid composition in the transplanted donor heart. The data indicate that providing dietary n-3 polyunsaturated fatty acids before and after cardiac transplant to recipient animals provides a significant protection against acute rejection.     

The eventration syndrome: prostacyclin liberation and acute hypoxemia due to eventration of the small intestine

In 13 patients undergoing infrarenal aortic bypass operation under neuroleptic anaesthesia, prostaglandins (KH2PGF2 alpha, PGF2 alpha, 6-keto-PGF1 alpha) and thromboxane (TXB2) were measured immediately prior to, 5 min after and 15 min after eventration of the gut. Blood gas analyses were performed at the same points in time. The levels of PGF2 alpha, although slightly elevated, remained stable, as did the levels of TXB2 (more than half the values being below the limit of detection). In 9 patients there was an immediate increase in the level of 6-keto-PGF1 alpha (a stable metabolite of prostacyclin), associated with a significant fall in the arterial oxygen tension. In 4 patients, the levels of 6-keto-PGF1 alpha remained low and no decrease in arterial oxygen tension was observed. KH2PGF2 alpha levels remained within the normal range, indicating that there was no stimulation of general prostaglandin secretion, but an isolated release of prostacyclin. In 7 patients, a mild, moderate or pronounced flush developed which did not, however, correlate to increases in the concentration of 6-keto-PGF1 alpha. These findings indicate that eventration of the gut is followed by prostacyclin liberation in considerable amounts due to the manipulation involved or to the impairment of the intestinal circulation. The concomitant fall in the oxygen tension is caused by pulmonary vasodilation, which increases the perfusion of underventilated parts of the lung.     

Comparative efficacy of dietary treatments on renal function in rats with sub-total nephrectomy: renal polyunsaturated fatty acid incorporation and prostaglandin excretion

The efficacy of dietary intervention with either 6% protein restriction, fish oil or safflower oil was assessed in the remnant nephron model. Female Munich Wistar rats were prefed for one week prior to 5/6 nephrectomy and followed for the ensuing 28 days. Fish oil, safflower oil and protein restriction prevented the gammaglobulinuria but only fish oil lessened the albuminuria in this model. The remnant nephrons of the fish oil treated rats contained less arachidonic acid and greater quantities of eicosapentaenoic and docosahexaenoic acid than the safflower oil or lab chow fed control rats. The fish oil, and to a lesser extent the safflower oil, treated animals had a higher ratio of 6 keto PGF1 alpha to TX B2 metabolites in their urine. We suggest these changes may be responsible for the lessening in urine protein excretion. Fish oil feeding was more effective than severe protein restriction or safflower oil dietary supplementation in lessening both the gammaglobulinuria and albuminuria of the remnant nephron model.     

The protective role of eicosapentaenoic acid [EPA] in the pathogenesis of nephrolithiasis

The low incidence of atherosclerosis and other degenerative diseases including stone disease in the Greenland Eskimo has been attributed to their high consumption of oily fish with its high concentration of eicosapentaenoic acid (EPA). Man cannot synthesis EPA from the precursor essential fatty acid, linolenic acid, and can only assimilate preformed EPA present in fish and fish oil, to bring about a change in the pathway of eicosanoid metabolism from the n-6 to the n-3 series. With a westernised diet the oxygenated products of renal prostaglandin synthesis are metabolites of the n-6 series and these are known to play an important role in several pathophysiological states including stone disease. Our previous studies have shown a relationship between prostaglandin activity and urinary calcium excretion and it would seem that the initiating factor/s for stone formation trigger the mechanisms for prostaglandin synthesis resulting in the biochemical abnormalities associated with stone disease. The Eskimo may be protected from these events by possession of an eicosanoid metabolism that follows an n-3 pathway. To test this hypothesis experiments were performed using an animal model of nephrocalcinosis. The animals were divided into three groups; one group was given an intra-peritoneal injection of 10% calcium gluconate daily for 10 days to induce nephrocalcinosis; a second group was fed MaxEPA fish oil before and during the calcium gluconate injections and a third group only received an intra-peritoneal injection of N saline. A group of 12 recurrent, hypercalciuric/hyperoxaluric stone-formers were treated with fish oil for eight weeks to study the effects on solute excretion. Nephrocalcinosis, which was readily produced in the control animals, was prevented in the experimental animals by pre-treatment with fish oil and urine calcium excretion was significantly reduced. The urinary calcium and oxalate excretion in the recurrent, hypercalciuric stone-formers was significantly reduced with fish oil treatment over an eight week period. There were no untoward side-effects. These studies indicate that the incorporation of EPA in the diet as a substitute metabolic pathway could be a unique way of correcting the biochemical abnormalities of idiopathic urolithiasis.     

n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent manner

Recent studies have suggested that n-3 fatty acids, abundant in fish oil, protect against high-fat diet-induced insulin resistance through peroxisome proliferator-activated receptor (PPAR)-alpha activation and a subsequent decrease in intracellular lipid abundance. To directly test this hypothesis, we fed PPAR-alpha null and wild-type mice for 2 weeks with isocaloric high-fat diets containing 27% fat from either safflower oil or safflower oil with an 8% fish oil replacement (fish oil diet). In both genotypes the safflower oil diet blunted insulin-mediated suppression of hepatic glucose production (P < 0.02 vs. genotype control) and PEPCK gene expression. Feeding wild-type mice a fish oil diet restored hepatic insulin sensitivity (hepatic glucose production [HGP], P < 0.002 vs. wild-type mice fed safflower oil), whereas in contrast, in PPAR-alpha null mice failed to counteract hepatic insulin resistance (HGP, P = NS vs. PPAR-alpha null safflower oil-fed mice). In PPAR-alpha null mice fed the fish oil diet, safflower oil plus fish oil, hepatic insulin resistance was dissociated from increases in hepatic triacylglycerol and acyl-CoA but accompanied by a more than threefold increase in hepatic diacylglycerol concentration (P < 0.0001 vs. genotype control). These data support the hypothesis that n-3 fatty acids protect from high-fat diet-induced hepatic insulin resistance in a PPAR-alpha-and diacylglycerol-dependent manner.     

Mesangial cells release untransformed prostaglandin H2 as a major prostanoid

BACKGROUND: Prostaglandin H2 (PGH2) is the precursor of the other prostanoids and exhibits a vasoconstricting activity. Glomerular mesangial cells are an important source of vasoactive prostanoids in kidney. Hence, the present investigation focused on the release of untransformed PGH2 by rat glomerular mesangial cells (RGMCs). METHODS: Synthesis of prostanoid by resting and interleukin-1beta (IL-1beta)-treated (overnight) RGMCs from exogenous or endogenous arachidonic acid (AA) was assessed by high-performance liquid chromtography or enzyme immunoassay, respectively. Cyclo-oxygenase isoforms were determined by Western blotting. Release of untransformed PGH2 from exogenous AA was evaluated in RGMCs and intact glomeruli as the difference of PGF2alpha formed in the incubations performed in the presence and in the absence of SnCl2 or measuring the ability of aspirin-treated platelets to form thromboxane B2 (TXB2) in mixed incubations of platelets and RGMCs or glomeruli. RESULTS: The prostanoids formed by RGMCs were PGE2, PGF2alpha, PGI2 and PGD2. SnCl2 totally deviated formation of PGE2 and PGD2 toward PGF2alpha in resting RGMCs, whereas PGE2 was only partially deviated toward PGF2alpha in IL-1beta-treated RGMCs. The PGE2/PGD2 ratio in resting RGMCs was similar to that expected for nonenzymatic isomerization of PGH2, whereas this ratio was higher in IL-1beta-treated RGMCs, suggesting the induction of PGE synthase by IL-1beta. Aspirin-treated platelets formed TXB2 when either RGMCs or intact glomeruli were present in the incubation and formation of TXB2 was approximately fourfold higher with IL-1beta-treated RGMCs or glomeruli. CONCLUSIONS: RGMCs and intact glomeruli released substantial amounts of untransformed PGH2, which was enhanced following exposure to IL-1beta.     

Changes in urinary prostaglandins during cardiopulmonary bypass in man

We measured urinary and plasma levels of thromboxane B2 (TXB2), 6-keto PGF1 alpha and urinary NAG during cardiopulmonary bypass (CPB) and studied their clinical significance. Subjects studied were 10 patients undergoing coronary artery bypass graft. Urinary and plasma levels of TXB2 and 6-keto PGF1 alpha increased during CPB. However, predictive plasma levels of TXB2 and 6-keto PGF1 alpha, calculated by urinary excretion, were higher than actual plasma levels. This result suggests that the kidney produces TXA2 and PGI2. Significant correlation (r = 0.87, P less than 0.01) was observed between NAG and TXB2 during CPB. The results suggest that TXA2 impairs the function of the renal urinary tubules.     

Lipid mediated modification of rat heart allograft survival

The effect on allograft survival of intravenous fat emulsions that differed in the ratio of functionally important n-3 and n-6 fatty acids was studied in a heterotopic cardiac transplant model in rats. Twenty percent fat emulsions were administered by continuous infusion at a dosage of 9 g fat/kg body weight per day, starting immediately after transplantation and continuing until complete rejection. The n-6 and n-3 fatty acids represent 75%, 43%, 60%, and 59% of all fatty acids in safflower oil, fish oil, soybean oil, and a 1:1 mixture of safflower and fish oil, respectively. The n-6 fatty acids predominate in safflower oil (370/1) and soybean oil (6.5/1), while the n-3 fatty acids dominate in the fish oil (7.6/1). The 1:1 mixture of safflower and fish oil has the balanced composition (n-6/n-3=2.1/1) recommended by Kinsella and served as oil-treated controls. Continuous infusion of safflower oil, fish oil, and soybean oil prolonged graft survival time to 13.3, 12.3, and 10.4 days, respectively, compared to 6.8 days in the oil-treated controls (P<0.01 for all comparisons). Another control group infused with saline rejected the allografts after 7.8 days (P=NS compared to oil-treated controls; P<0.01 for all other comparisons). The data suggest that intravenous administration of polyunsaturated fat emulsions results in an immunosuppressive effect that seems to be dependent on the n-3/n-6 fatty acid ratio of the fat emulsion. The n-6 fatty acids turned out to be just as immunosuppressive as the n-3 fatty acids if each fatty acid family was applied as the main polyunsaturated fatty acid source. Soybean oil with a n-3/n-6 fatty acid ratio, coming closer to the ratio of the oil-treated controls, was significantly less immunosuppressive than safflower oil.     

Fatty acid composition and arachidonic acid concentrations in alveolar bone of rats fed diets with different lipids

Summary The purpose of the present study was to determine if the type of dietary fat can modify the fatty acid composition and arachidonic acid levels in the alveolar bone phospholipids. Three groups of rats were fed nutritionally adequate semipurified diets containing different lipids: 10% corn oil (control, group 1, rich in n-6 fatty acids); 9% butter + 1% corn oil (experimental, group 11, rich in saturated fatty acids); and 9% ethyl ester concentrate of n-3 fatty acids + 1% corn oil (experimental, group 111, rich in n-3 fatty acids). After 10 weeks of feeding the various diets, rats were killed, maxillae and mandibles were dissected out, and the soft tissue was removed. Bone was frozen in liquid nitrogen and pulverized. Powdered bone was extracted for total lipids, and phospholipids were isolated by column chromatography. The fatty acid composition and arachidonic acid concentrations were determined in total phospholipids after the addition of an internal standard, octadecatetraenoic acid (18: 4n-3), and subsequent gas chromatography. The type of dietary lipids had a profound influence on the fatty acid composition of bone lipids. Arachidonic acid concentrations were significantly lower in total phospholipids of mandibles and maxillae of rats fed the experimental diets than in those fed the control diet. Because arachidonic acid is a precursor of prostaglandin E₂ and leukotriene C₄, a significant reduction in its concentration may result in reduced levels of these eicosanoids in the alveolar bone.Presented in part at the International Association for Dental Research Meeting, Glasgow, Scotland, July 1–4, 1992     

Profiles of endogenous prostaglandin F2 alpha, thromboxane A2 and prostacyclin with regard to cardiovascular and organ functions in early septic shock in man

15 out of 68 patients with severe sepsis were examined in an early stage of shock and analyzed for objective hemodynamic and functional shock criteria. These data were correlated to endogenous plasma concentrations of the vasoactive arachidonate derivatives: prostaglandin F2 alpha (PGF2 alpha), thromboxane A2 (TXA2) and prostacyclin (PGI2). Marked differences in invasively measured data of cardiac, pulmonary and renal functions divided clinically otherwise comparable patients into group I and II. Group I was characterized by a hypodynamic response as compared to group II which was hyperdynamic. In spite of similar levels of PGF2 alpha (570 +/- 80 vs. 560 +/- 103 pg/ml) in both groups indicating a comparable state of arachidonate turnover, opposing profiles with regard to the TXA2/PGI2 ratio as measured from their stable degradation products were found (TXB2 [I]: a 740 +/- 184; TXB2 [II]: 280 +/- 75; 6-k-PGF1 alpha [I]: 260 +/- 117; 6-k-PGF1 alpha [II]: 940 +/- 190 pg/ml). It is concluded that early sepsis in man leads to variable profiles of endogenously released prostaglandins and thromboxane in which the predominance of PGI2 over TXA2 is associated with better cardiovascular performance and organ functions, and vice versa.     

Urinary prostaglandins and thromboxane in patients with chronic glomerulonephritis

To evaluate the potential contribution of prostaglandins (PGs) and thromboxane (TX) to the development of chronic glomerulonephritis, we measured the urinary excretion of PGE, PGF2 alpha, 6-keto-PGF1 alpha and TXB2 by radioimmunoassay in 36 patients with chronic glomerulonephritis. In patients with nephrotic syndrome, urinary excretion of PGE and TXB2 was highly increased, whereas that of PGF2 alpha and 6-keto-PGF1 alpha remained normal. In patients with non-nephrotic chronic glomerulonephritis, urinary excretion of TXB2 was significantly increased, whereas that of PGE and 6-keto-PGF1 alpha remained normal and that of PGF2 alpha was significantly decreased. In patients with chronic renal failure, the urinary excretion of all PGS and TX was markedly decreased presumably due to a decrease in the number of cells which can metabolize arachidonic acid. These results suggest that TXA2 plays an important role as an exaggerating factor in the development of chronic glomerulonephritis, particularly that accompanying nephrotic syndrome, and that renal synthesis of PGE is compensatorily increased to maintain renal function in nephrotic syndrome.     

Effects of dietary fish oil on renal insufficiency in rats with subtotal nephrectomy

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.     

Effects of subarachnoid hemorrhage and a thromboxane A2 synthetase inhibitor on intracranial prostaglandins

The effects of subarachnoid hemorrhage (SAH) on intracranial prostaglandins (PGs) were studied in canines. Subarachnoid hemorrhage was produced by the "two hemorrhage" method. Basilar artery caliber and regional cerebral blood flow (rCBF) in the occipital cortex were reduced by 42% and 43% during delayed vasospasm, respectively. Once delayed vasospasm had developed, intravenous infusion of OKY-046, a selective inhibitor of thromboxane (TX) A2 synthetase, induced no significant change in angiographic vasospasm but caused a significant increase in rCBF. In delayed vasospasm, cortical levels of PGF2 alpha were significantly decreased, whereas plasma levels of PGF2 alpha and TXB2 in the transverse sinus were significantly increased. The intravenous infusion of OKY-046 in delayed vasospasm induced a significant increase in cortical PGF2 alpha and PGE in the occipital cortex, and caused a significant increase in plasma 6-keto-PGF1 alpha and a significant decrease in plasma TXB2 in the transverse sinus. In delayed vasospasm, decreased cortical levels of PGF2 alpha may reflect a decrease in rCBF and increased plasma PGF2 alpha and TXB2 levels may reflect enhancement of intravascular coagulation. These PGs have very strong and various biological activities. The results suggest that SAH induces complicated changes of intracranial PGs and OKY-046 can improve these pathological changes.     

Fatty acid composition of some South African fresh-water fish

Because of the antithrombotic and anti-inflammatory properties of the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are found in large quantities in marine fish, the fatty acid composition of the flesh of 18 different species of fresh-water fish found in South Africa was analysed by capillary gas chromatography. In general all the fish studied had low percentages of EPA and DHA and fairly high percentages of arachidonic acid and linoleic acid when compared with some marine fish. The saturated fats constituted 33% of total fatty acids and the mono-enes averaged 35%. The fish studied are therefore not as good a source of n-3 fatty acids as marine fish.     

Fatty acid intake and Kupffer cell function: fish oil alters eicosanoid and monokine production to endotoxin stimulation

Diets high in n-3 fatty acids appear to have an anti-inflammatory effect, which is thought to be due to decreased macrophage prostaglandin (PG) and thromboxane (Tx) production after incorporation of these fatty acids into cell membrane phospholipids. The effect of n-3 fatty acids incorporation on macrophage monokine release in response to septic stimuli is not well established. Kupffer cells, the fixed macrophages of the liver, were obtained from rats fed diets with fat sources derived from corn oil (CO, control), fish oil (FO, high in n-3 fatty acids), or safflower oil (SO, high in n-6 fatty acids) for 2 or 6 weeks. After exposure to bacterial lipopolysaccharide, Kupffer cells from rats fed FO for 2 or 6 weeks produced less PG and Tx than Kupffer cells from rats fed CO or SO. After 2 weeks of defined diets, interleukin-1 (IL-1) and tumor necrosis factor release were not affected by dietary fat source. In contrast, after 6 weeks of feeding, Kupffer cells from both the FO and the SO groups released less IL-1 and tumor necrosis factor when triggered by lipopolysaccharide than Kupffer's cells from animals fed the control diet that contained CO. These data suggest that altered monokine release from macrophages may contribute to the anti-inflammatory effect of diets high in n-3 fatty acids. Also shown in our results is that prolonged changes in membrane phospholipid content induced by dietary fat source can influence not only PG and Tx production but monokine release as well.