Contribution of meat fat to dietary arachidonic acid

Arachidonic acid (AA) in the diet can be efficiently absorbed and incorporated into tissue membranes, resulting in an increased production of thromboxane A₂ by platelets and increased ex vivo platelet aggregability. Results from previous studies have shown that AA is concentrated in the membrane phospholipids of lean meats. However, the concentration of AA in the visible fat portion of meats also may be significant despite being ignored in most studies. The aim of this study was to accurately quantitate the AA content of visible fat and the lean portion of beef, lamb, pork, chicken, duck, and turkey. The visible fat of meat contained a significant quantity of AA, ranging from 20 to 180 mg/100 g fat, whereas the AA content of the lean portion of meat was lower, ranging from 30 to 99 mg/100 g lean meat. Beef and lamb meats contained lower levels of AA in both the visible fat and lean portion than that from the other species. The highest level of AA in lean meat was in duck (99 mg/100 g), whereas pork fat had the highest concentration for the visible fats (180 mg/100 g). The lean portions of beef and lamb contained the higher levels of n-3 polyunsaturated fatty acids (PUFA) compared with white meats which were high in AA and low in n-3 PUFA. The present data indicate that the visible meat fat can make a contribution to dietary intake of AA, particularly for consumers with high intakes of fat from pork or poultry meat.     

Evidence that dietary arachidonic acid increases circulating triglycerides

Male Syrian hamsters and male CD-1 mice were fed diets supplemented with ethyl esters of oleic, linoleic, arachidonic, and eicosapentaenoic acids (1.1–1.5%, w/w) for 3–4 wk. Plasma and serum triglycerides were significantly higher in the arachidonic acid-supplemented animals compared to those in the other supplementation groups. Changes in serum insulin and glucose levels did not appear to be related to the changes in circulating triglycerides observed in the arachidonic acid-supplemented group. These data indicate that dietary arachidonic acid elevates circulating triglyceride levels compared to other unsaturated fatty acids in hamsters and mice by unknown mechanisms. This work was presented at the 78th Annual Meeting of the Federation of American Societies for Experimental Biology, April 1994, Anaheim, CA.     

Effects of dietary 9-trans, 12-trans linoleate on arachidonic acid metabolism in rat platelets

In order to determine the minimal amount of dietary 9-trans,12-trans-linoleate which can decrease endoperoxide metabolites synthesized and their precursor in rat platelets, graded amounts (0, 0.1, 0.5, 1.0, 2.5%) of thetrans-linoleate were fed to rats with a constant amount of all-cis-linoleate (2.5%) for 12 weeks. Arachidonic acid levels in platelet phospholipids of groups receiving thetrans-linoleate at 2.5 and 1.0% were significantly (p<0.01) lower than that of the control receiving notrans-linoleate. Concentrations of TXB₂ and PGF_2α in sera of the group receiving 2.5%trans-linoleate were significantly (p<0.05) lower than those of the control; however, there was no difference between the group receiving 1.0%trans-linoleate and the control. To determine whether the difference in serum concentrations of endoperoxide metabolites could be manifested if rats were fed for longer period of time, 2 groups of rats were again fed diets containing 0 and 1.0%trans-linoleate, respectively, for 16 weeks. Arachidonic acid in platelet phospholipids of the group receiving thetrans-linoleate was again significantly (p<0.01) lower than that of the control group. Concentrations of TXB₂ and PGF_2α, and 12-hydroxyeicosatetraenoic acid formed in platelets, were smaller in the group receivingtrans-linoleate than the control group; however, the difference was not statistically significant. These results indicated that all-trans-linoleate can reduce arachidonic acid metabolites formed in rat platelets when its dietary level is equal to or exceeds the level of all-cis-linoeate.     

Effect of maternal dietary arachidonic or linoleic acid on rat pup fatty acid profiles

Rapidly growing neonatal mammals accrete relatively large quantities of long chain (≥C₂₀) polyunsaturated fatty acids (LCP) in membrane phospholipids. We have examined accumulation of ω6 LCP in suckling neonatal rat pups during the first 14 d of life when their dams received essential fatty acids in the form of triglycerides containing linoleic acid or arachidonic acid. Dietary levels of these fatty acids were either 1 or 5% of total dietary fatty acids. The fatty acid profile of pup stomach contents (composed solely of the dams' milk) and plasma lipids, as well as liver and brain phospholipids, were determined. Stomach linoleic and arachidonic acid levels reflected the diet of the dams. Pup plasma and liver arachidonic acid levels increased progressively from the group receiving 1% linoleic acid to 5% linoleic acid and from 1% arachidonic acid to 5% arachidonic acid. Interestingly, brain phosphatidylethanolamine and phosphatidylcholine arachidonic acid levels were more stable than plasma or liver levels. These results suggest that the brain may be capable of either selective transport of ω6 LCP or chain elongation/desaturation of linoleic acid. These data indicate that care must be exercised when adding LCP to infant formula since widely divergent accretion rates of arachidonic acid may occur in various tissues.     

Effect of dietary arachidonic acid on metabolism of deuterated linoleic acid by adult male subjects

The influence of dietary supplementation with 20:4n−6 on uptake and turnover of deuterium-labeled linoleic acid (18:2n−6[d ₂]) in human plasma lipids and the synthesis of desaturated and elongated n−6 fatty acids from 18:2n−6[d ₂] were investigated in six adult male subjects. The subjects were fed either a high-arachidonic acid (HIAA) diet containing 1.7 g/d or a low-AA (LOAA) diet containing 0.21 g/d of AA for 50 d. Each subject was then dosed with about 3.5 g of 18:2n−6[d ₂] as the triglyceride (TG) at 8:00 a.m., 12:00, and 5:00 p.m. The total 18:2n−6[d ₂] fed to each subject was about 10.4 g and is approximately equal to one-half of the daily intake of 18:2n−6 in a typical U.S. male diet. Nine blood samples were drawn over a 96-h period. Methyl esters of plasma total lipid (TL), TG, phospholipid, and cholesterol ester were analyzed by gas chromatography-mass spectroscopy. Dietary 20:4n−6 supplementation did not affect uptake of 18:2n−6[d ₂] in plasma lipid classes over the 4-d study period nor the estimated half-life of 24–36 h for 18:2n−6[d ₂]. The percentages of major deuterium-labeled desaturation and elongation products in plasma TL, as a percentage of total deuterated fatty acids, were 1.35 and 1.34% 18:3n−6[d ₂]; 0.53 and 0.50% 20:2n−6[d ₂]; 1.80 and 0.92% 20:3n−6[d ₂] and 3.13 and 1.51% 20:4n−6[d ₂] for the LOAA and HIAA diet groups, respectively. Trace amounts (<0.1%) of the TL concentration data for both 20:3n−6[d ₂] and 20:4n−6[d ₂] were 48% lower (P<0.05) in samples from the HIAA diet group than in samples from the LOAA diet group. For a normal adult male consuming a typical U.S. diet, the estiamted accumulation in plasma TL of 20:4n−6 synthesized from 20 g/d (68 mmole) of 18:2n−6 is 677 mg/d (2.13 mmole). Dietary supplementation with 1.5 g/d of 20:4n−6 reduced accumulation of 20:4n−6 synthesized from 20 g/d of 18:2n−6 to about 326 mg/d (1.03 mmole).     

A human dietary arachidonic acid supplementation study conducted in a metabolic research unit: Radionale and design

While there are many reports of studies that fed arachidonic acid (AA) to animals, there are very few reports of AA feeding to humans under controlled conditions. This 130-d study was conceived as a controlled, symmetrical crossover design with healthy, adult male volunteers. They lived in the metabolic research unit (MRU) of the Western Human Nutrition Research (WHNRC) for the entire study. All food was prepared by the WHNRC kitchen. The basal (low-AA) diet consisted of natural foods (30 en% fat, 15 en% protein, and 55 en% carbohydrate), containing 210 mg/d of AA, and met the recommended daily allowance for all nutrients. The high-AA (intervention) diet was similar except that 1.5 g/d of AA in the form of a triglyceride containing 50% AA replaced an equal amount of high-oleic safflower oil in the basal diet. The subjects (ages 20 to 39) were within −10 to +20% of ideal body weight, nonsmoking, and not allowed alcohol in the MRU. Their exercise level was constant, and their body weights were maintained within 2% of entry level. Subjects were initially fed the low-AA diet for 15 d. On day 16, half of the subjects (group A) were placed on the high-AA diet, and the other group (B) remained on the low-AA diet. On day 65, the two groups switched diets. On day 115, group B returned to the low-AA diet. This design, assuming no carryover effect, allowed us to merge the data from the two groups, with the data comparison days being 65 (low-AA) and 115 (high-AA) for group B and 130 (low-AA) and 65 (high-AA) for group A. The main indices studied were the fatty acid composition of the plasma, red blood cells, platelets, and adipose tissue; in vitro platelet aggregation, bleeding times, clotting factors; immune response as measured by delayed hypersensitivity skin tests, cellular proliferation of peripheral blood mononuclear cells in response to various mitogene and antigens, natural killer cell activity, and response to measles/mumps/rubella and influenza vaccines; the metabolic conversion of deuterated linoleic acid to AA and the metabolic fate of deuterated AA in the subjects on and off the high-AA diet; and the production of eicosanoids as measured by excretion of 11-DTXB₂ and PGI₂-M in urine. The results of these studies with be presented in the next five papers from this symposium.     

Increased dietary arachidonic acid enhances the synthesis of vasoactive eicosanoids in humans

Data on the effect of dietary arachidonic acid (AA) (20∶4n-6) on the synthesis of thromboxane and prostacyclin (PGI₂) in humans are lacking. We measured the effect of 1.5 g/d (ca. 0.5 en%) of 20∶4n-6 added isocalorically to a stabilization (low-AA) diet on the excretion of 11-dehydrothromboxane B₂ (11-DTXB₂) and 2,3-dinor-6-oxo-PGF_1α (PGI₂-M). In a crossover design, 10 healthy men, living in a metabolic unit, were fed a diet (low-AA) containing 210 mg/d of 20∶4n-6 for 65 d and an identical diet (high-AA) that contained 1.5 g/d of additional 20∶4n-6 for 50 d. Three-day urine pools were collected at the end of each dietary period and analyzed for eicosanoids by gas chromatography-electron capture negative ion-tandem mass spectrometry. Mean excretion of 11-dehydrothromboxane B₂ was 515±76, 493±154, and 696±144 ng/d (SD; n=10) during the acclimation (15 d) low-AA diet and high-AA diet periods, respectively (41% increase from low-AA to high-AA diet, P=0.0037); mean excretion of PGI₂-M was 125±40, 151±36, and 192±55 ng/d (SD; n=10) during acclimation (15 d) low-AA and high-AA diets, respectively (27% increase from low-AA to high-AA diets; P=0.0143). Thus, both the metabolites of thromboxane and PGI₂ increase on the high-AA diet. Furthermore, both indicated changes in metabolite excretion may be associated with measurable effects on several physiologically significant cellular functions, such as platelet aggregation in vivo and inflammation in response to immune challenges.     

Effects of arachidonic acid supplementation on training adaptations in resistance-trained males

Background

To determine the impact of AA supplementation during resistance training on body composition, training adaptations, and markers of muscle hypertrophy in resistance-trained males.

Methods

In a randomized and double blind manner, 31 resistance-trained male subjects (22.1 ± 5.0 years, 180 ± 0.1 cm, 86.1 ± 13.0 kg, 18.1 ± 6.4% body fat) ingested either a placebo (PLA: 1 g·day^-1 corn oil, n = 16) or AA (AA: 1 g·day^-1 AA, n = 15) while participating in a standardized 4 day·week^-1 resistance training regimen. Fasting blood samples, body composition, bench press one-repetition maximum (1RM), leg press 1RM and Wingate anaerobic capacity sprint tests were completed after 0, 25, and 50 days of supplementation. Percutaneous muscle biopsies were taken from the vastus lateralis on days 0 and 50.

Results

Wingate relative peak power was significantly greater after 50 days of supplementation while the inflammatory cytokine IL-6 was significantly lower after 25 days of supplementation in the AA group. PGE₂ levels tended to be greater in the AA group. However, no statistically significant differences were observed between groups in body composition, strength, anabolic and catabolic hormones, or markers of muscle hypertrophy (i.e. total protein content or MHC type I, IIa, and IIx protein content) and other intramuscular markers (i.e. FP and EP₃ receptor density or MHC type I, IIa, and IIx mRNA expression).

Conclusion

AA supplementation during resistance-training may enhance anaerobic capacity and lessen the inflammatory response to training. However, AA supplementation did not promote statistically greater gains in strength, muscle mass, or influence markers of muscle hypertrophy.     

High levels of dietary arachidonic acid triglyceride exhibit no subchronic toxicity in rats

Arachidonic acid (AA), an n?6 long-chain polyunsaturated fatty acid (LC-PUFA), serves an important role in the body as a structural fatty acid of many tissues including neurological tissues. It is also a precursor of the n?6 class of eicosanoids and is the most abundant n?6 LC-PUFA found in human breast milk. We have optimized the production of a microfungal source of a triglyceride oil (ARASCO^®) which is enriched in AA to about 40% by weight. To establish the safety of this oil as a food, we evaluated the effect of ARASCO^® in Sprague-Dawley rats (20/sex/group) gavaged at dose levels of 1.0 and 2.5 g/kg/d for a period of 90 d, paying special attention to any potential neurotoxicity of the oil. Two groups of control animals received either untreated standard laboratory diet (untreated control) or the same diet and vehicle oil at the same dose volume administered to the treated animals (vehicle control). Physical observations, ophthalmoscopic examinations, body weight, food consumption, clinical chemistry, hematology parameters, neurobehavioral assessments, and macroscopic as well as microscopic postmortem evaluations were performed. Tissue fatty acid analyses indicated that the AA levels in the brain, heart, and liver of the high-dose ARASCO^®-fed animals increased by 8, 59, and 76%, respectively, indicating that the AA in the oil was readily incorporated into tissue lipids. In spite of this high elevation in tissue AA levels, no developmental, histopathological, or neuropathological differences were seen in the animals administered ARASCO^® compared with the vehicle control animals. Being highly enriched in AA, ARASCO^® offers the means to study the effect of this fatty acid in experimental settings and in human metabolic studies.     

Modulation of adjuvant-induced arthritis by dietary arachidonic acid in essential fatty acid-deficient rats

Controlled feeding of linoleic acid (LA) or arachidonic acid (AA) to essential fatty acid-deficient (EFAD) rats was used to define the relationship between dietary AA and the inflammatory response evoked during adjuvant-induced arthritis. Based on energy percentage, EFAD rats were fed AA at the human daily equivalent (1×; 5.5 mg/day) or 10 times that amount (10×; 55 mg/day) or, alternatively, 0.5× of LA (273 mg/day). Feeding of 0.5×LA restored the plasma level of AA to that in chow-fed controls. In contrast, feeding of 1×AA only partially restored the plasma level of AA; 10×AA was required to fully replete AA. In parallel to the degree of repletion of AA in plasma, there were accompanying decreases in the levels of palmitoleic acid, oleic acid, and Mead acid. Compared to rats fed the standard laboratory chow diet (Control), edema in the primary hind footpads was decreased by 87% in EFAD, 71% in EFAD+1×AA, 45% in EFAD+10×AA, and 30% in EFAD+0.5×LA. The decrease in edema in the footpads of EFAD rats was nearly identical to the decrease in edema in the footpads of Control rats dosed with indomethacin. Hind footpad edema correlated with the final AA plasma level and eicosanoid levels extracted from hind footpad tissue, but not with neutrophil infiltration. The data showed that 0.5×LA and 10×AA, but not 1×AA, could quickly replete AA, accompanied by the synthesis of AA-derived eicosanoids and restoration of edema. These results suggest that in humans consumption of the average daily amount of AA without concurrent ingestion of LA would not alleviate an EFAD state.     

Effect of degree of unsaturation in dietary fatty acids on arachidonic acid mobilization by peritoneal macrophages

Cells from rats fed with a tripalmitin diet showed a depletion of phospholipid arachidonate and n-3 fatty acids such as eicosapentaenoic and docosahexaenoic acids (EPA and DHA). In rats fed fish oil diet, a significant reduction in archidonic acid (AA) content was observed whereas EPA and DHA were incorporated into membranes lipids. These changes in lipid composition of membranes did not affect cellular adherence, phagocytic capability, or [³H]AA incorporation. However, both tripalmitin and fish oil diets induced a decrease in [³H]AA mobilization stimulated by 4β-phorbol-12-myristate 13-acetate, A23187, or opsonized-zymosan in rat peritoneal macrophages. These results demonstrate that the antiinflammatory effects of essential fatty acids deficiency or n-3 enrichment diets may be associated with a decreased AA mobilization in resident rat peritoneal macrophages treated with proinflammatory agents.     

The effect of peroxidized arachidonic acid upon human platelet aggregation

Human platelet aggregation was studied in vitro following exposure to free arachidonic acid and peroxidized arachidonic acid. A slow aggregation response was caused by free arachidonic acid, whereas a rapid, marked response resulted from exposure to peroxidized free arachidonic acid. Aggregation resulting from peroxidized arachidonic acid was not counteracted by adenosine nor by prostaglandin E₁, both in high concentrations. Peroxide-induced platelet aggregation required the presence of added calcium ions in vitro. The aggregation resulting from exposure to peroxidized arachidonic acid was abolished by prior treatment of the lipid peroxide with tocopherol and butylated hydroxy toluenne.     

The effect of dietary arachidonic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans

Arachidonic acid (AA) is the precursor of thromboxane and prostacyclin, two of the most active compounds related to platelet function. The effect of dietary AA on platelet function in humans is not understood although a previous study suggested dietary AA might have adverse physiological consequences on platelet function. Here normal healthy male volunteers (n=10) were fed diets containing 1.7 g/d of AA for 50 d. The control diet contained 210 mg/d of AA. Platelet aggregation in the platelet-rich plasma was determined using ADP, collagen, and AA. No statistical differences could be detected between the aggregation before and after consuming the high-AA diet. The prothrombin time, partial thromboplastin time, and the antithrombin III levels in the subjects were determined also. There were no statistically significant differences in these three parameters when the values were compared before and after they consumed the high-AA diet. The in vivo bleeding times also did not show a significant difference before and after the subjects consumed the high-AA diet. Platelets exhibited only small changes in their AA content during the AA feeding period. The results from this study on blood clotting parameters and in vitro platelet aggregation suggest that adding 1.5 g/d of dietary AA for 50 d to a typical Western diet containing about 200 mg of AA produces no observable physiological changes in blood coagulation and thrombotic tendencies in healthy, adult males compared to the unsupplemented diet. Thus, moderate intakes of foods high in AA have few effects on blood coagulation, platelet function, or platelet fatty acid composition.     

Influence of dietary arachidonic acid on metabolism in vivo of 8 cis, 11 cis, 14-eicosatrienoic acid in humans

This study investigated the influence of dietary arachidonic acid (20∶4n-6) on Δ5 desaturation and incorporation of deuterium-labeled 8cis, 11cis, 14-eicosatrienoic acid (20∶3n-6) into human plasma lipids. Adult male subjects (n=4) were fed diets containing either 1.7 g/d (H120∶4 diet) or 0.21 g/d (LO20∶4 diet) of arachidonic acid for 50 d and then dosed with a mixture containing ethyl esters of 20∶3n-6[d4] and 18∶1n-9[d2]. A series of blood samples was sequentially drawn over a 72-h period, and methyl esters of plasma total lipid, triacylglycerol, phospholipids, and cholesteryl ester were analyzed by gas chromatography-mass spectrometry. Based on the concentration of 20∶3n-6[d4] in total plasma lipid, the estimated conversion of 20∶3n-6[d4] to 20∶4n-6[d4] was 17.7.±0.79% (HI20∶4 diet) and 2.13±1.44% (LO20∶4 diet). The concentrations of 20∶4n-6[d4] in total plasma lipids from subjects fed the HI20∶4 and LO20∶4 diets were 2.10±0.6 and 0.29±0.2 μmole/mL plasma/mmole of 20∶3n-6[d4] fed/kg of body weight. These data indicate that conversion of 20∶3n-6[d4] to 20∶4n-6[d4] was stimulated 7-8-fold by the HI20∶4 diet. Phospholipid acyltransferase was 2.5-fold more selective for 20∶3n-6[d4] than 18∶1n-9[d2], and lecithin:cholesterol acyltransferase was 2-fold more selective for 18∶1n-9[d2] than 20∶3n-6[d4]. These differences in selectivity were not significantly influenced by diet. Absorption of ethyl 20∶3n-6[d4] was about 33% less than ethyl 18∶1n-9[d2]. The sum of the n-6 retroconversion products from 20∶3n-6[d4] in total plasma lipids was about 2% of the total deuterated fatty acids. Neither absorption nor retroconversion appears to be influenced by diet.     

唑来膦酸对甲型肝炎病毒抗原诱导小鼠体液免疫应答的影响

目的探讨唑来膦酸(zoledronic acid,ZOL)对甲型肝炎病毒(hapatitis A virus,HAV)抗原诱导小鼠体液免疫应答的影响。方法将不同剂量(10、20、40μg)的ZOL与HAV抗原(18 EU)混合,为ZOL不同剂量组,并设阴性对照组(生理盐水0.2 ml)、阳性对照组(HAV抗原18 EU)、铝佐剂对照组[HAV抗原(18 EU)+Al(OH)3(100μg)],均经皮下注射ICR小鼠,免疫4、8、12、16周后,经小鼠尾静脉采血,分离血清,采用ELISA法检测小鼠血清中抗HAV抗原特异性IgG抗体水平。免疫16周后,取ZOL 40μg组及阴性对照组小鼠心脏、肝脏、脾脏、肺脏、肾脏组织进行病理切片观察。结果除阴性对照组外,各ZOL剂量组小鼠免疫4周后,均产生抗-HAV IgG,并随着时间的延长呈上升趋势,于第8周后达到峰值,此后逐渐下降;ZOL不同剂量组的抗体水平均明显高于阳性对照组,差异有统计学意义(P0.05),免疫8周后,40μg组抗体水平最高,为1 079 EU;ZOL 40μg组免疫4和16周后的抗体水平高于铝佐剂对照组,但差异无统计学意义(P0.05),ZOL的最佳剂量为40μg/只。ZOL 40μg组小鼠心、肝、脾、肺、肾组织均未观察到病变。结论 ZOL可明显增强HAV抗原诱导小鼠的体液免疫应答。     

Effects of dietarytrans acids on the biosynthesis of arachidonic acid in rat liver microsomes

Effects of dietarytrans acids on the interconversion of linoleic acid was studied using the liver microsomal fraction of rats fed a semipurified diet containing fat supplements of safflower oil (SAFF), hydrogenated coconut oil (HCO) at 5 and 20% levels or a 5% level of a supplement containing 50.3% linolelaidic and 24.3% elaidic acids devoid ofcis,cis-linoleic acid (TRANS). Growth rate was suppressed to a greater extent with the animals fed the 20% than the 5% level of the HCO-supplemented diets and still further by the TRANS diet compared to the groups fed the SAFF diets. Food intake was greater in the groups fed the HCO than the SAFF-supplemented diets, demonstrating the marked effect of an essential fatty acid (EFA) deficiency on feed efficiency. In contrast to an EFA deficiency produced by the HCO supplement, which stimulated the in vitro liver microsomal biosynthesis of arachidonic acid, diets containing the TRANS supplement exacerabated the EFA deficiency and depressed 6-desaturase activity of the liver microsomal fraction. The liver microsomal fraction of the animals receiving this supplement also was more sensitive to fatty acid inhibition of the desaturation of linoleic acid than those obtained from animals fed either the SAFF or HCO diets. It is suggested that dietarytrans acids alter the physical properties of the 6-desaturase enzyme system, suppressing its activity, which increases the saturation of the tissue lipids and, in turn, the requirement for EFA or polyunsaturated fatty acids.     

Enhancement of eicosaenoic acid lipoxygenation in human platelets by 12-hydroperoxy derivative of arachidonic acid

Human platelet lipoxygenase activity toward several eicosaenoic acids was measured in intact cells as well as in subcellular fractions (cytosol and membranes). In whole platelets, the lipoxygenation of eicosaenoic acids was enhanced greatly by high concentrations of aspirin, which partially inhibit the peroxidase activity associated with the pathway. The lipoxygenation also was increased by arachidonic acid (AA) or its lipoxygenase product, 12-hydroxyperoxy-eicosatetraenoic acid (12-HPETE). Similarly, prostanoid precursors, dihomogammalinolenic (DHLA) and eicosapentaenoic (EPA) acids also were better converted by cyclooxygenase in the presence of AA or 12-HPETE. Among the eicosaenoic acids tested, EPA oxygenation was affected most. Using cytosol or membranes as the lipoxygenase source instead of whole cells led to completely different results. AA exerted a competitive inhibition upon the other eicosaenoic acid oxygenation except that of EPA, for which a dual effect of AA was observed. This makes questionable the use of platelet subfractions for investigating lipoxygenase activity. We conclude that platelet lipoxygenation of eicosaenoic acids appears peroxide-dependent, especially for apparent poor substrates like EPA. This might be relevant in respect to 12-HPETE, which is the main hydroperoxy derivative to be produced during platelet activation.