Serum Fatty Acid Profiles Are Associated with Disease Activity in Early Rheumatoid Arthritis: Results from the ESPOIR Cohort.

BACKGROUND: Long-chain omega-3 and omega-6 fatty acids (n-3, n-6 FAs) may modulate inflammation and affect the risk of developing rheumatoid arthritis (RA). However, whether n-3/n-6 FA status affects RA after disease onset is unknown. This study aimed to assess whether FA profiles are independently associated with disease activity in a large prospective cohort of patients with early RA. METHODS: Baseline serum FAs were quantified in 669 patients in the ESPOIR cohort. Principal component analysis identified three serum FA patterns that were rich in n-7-9, n-3 and n-6 FAs (patterns ω7-9, ω3 and ω6), respectively. The association of pattern tertiles with baseline variables and 6-month disease activity was tested using multivariable logistic regression. RESULTS: Pattern ω3 was associated with low baseline and pattern ω6 with high baseline C-reactive protein level and disease activity. Both patterns ω3 and ω6 were associated with reduced odds of active disease after 6 months of follow-up (pattern ω3: odds ratio, tertile three vs. one, 0.49 [95% CI 0.25 to 0.97] and pattern ω6: 0.51 [0.28 to 0.95]; p = 0.04 and 0.03, respectively). CONCLUSIONS: In a cohort of early RA patients, a serum lipid profile rich in n-3 FAs was independently associated with persistently reduced disease activity between baseline and 6-month follow-up. An n-6 FA profile was also associated with lower 6-month disease activity.

Whole Rye Consumption Improves Blood and Liver n-3 Fatty Acid Profile and Gut Microbiota Composition in Rats.

BACKGROUND: Whole rye (WR) consumption seems to be associated with beneficial health effects. Although rye fiber and polyphenols are thought to be bioactive, the mechanisms behind the health effects of WR have yet to be fully identified. This study in rats was designed to investigate whether WR can influence the metabolism of n-3 and n-6 long-chain fatty acids (LCFA) and gut microbiota composition. METHODS: For 12 weeks, rats were fed a diet containing either 50% WR or 50% refined rye (RR). The WR diet provided more fiber (+21%) and polyphenols (+29%) than the RR diet. Fat intake was the same in both diets and particularly involved similar amounts of essential (18-carbon) n-3 and n-6 LCFAs. RESULTS: The WR diet significantly increased the 24-hour urinary excretion of polyphenol metabolites-including enterolactone-compared with the RR diet. The WR rats had significantly more n-3 LCFA-in particular, eicosapentanoic (EPA) and docosahexanoic (DHA) acids-in their plasma and liver. Compared with the RR diet, the WR diet brought significant changes in gut microbiota composition, with increased diversity in the feces (Shannon and Simpson indices), decreased Firmicutes/Bacteroidetes ratio and decreased proportions of uncultured Clostridiales cluster IA and Clostridium cluster IV in the feces. In contrast, no difference was found between groups with regards to cecum microbiota. The WR rats had lower concentrations of total short-chain fatty acids (SCFA) in cecum and feces (p<0.05). Finally, acetate was lower (p<0.001) in the cecum of WR rats while butyrate was lower (p<0.05) in the feces of WR rats. INTERPRETATION: This study shows for the first time that WR consumption results in major biological modifications-increased plasma and liver n-3 EPA and DHA levels and improved gut microbiota profile, notably with increased diversity-known to provide health benefits. Unexpectedly, WR decreased SCFA levels in both cecum and feces. More studies are needed to understand the interactions between whole rye (fiber and polyphenols) and gut microbiota and also the mechanisms of action responsible for stimulating n-3 fatty acid metabolism.

Six-day selenium supplementation led to either UVA-photoprotection or toxic effects in human fibroblasts depending on the chemical form and dose of Se.

Selenium (Se) is an essential trace element with a narrow safety zone and unclear effects on skin photoageing. The aim of this work was to investigate the photoageing properties of sodium selenite or selenomethionine (SeMet) after a long term (6 days) Se supplementation in normal human skin fibroblasts (NHSF) subjected to ultraviolet-A (UVA) irradiation inducing 30% cell death. The uptake, toxicity and antioxidant effects of sodium selenite and SeMet were compared to better understand their photoageing properties. SeMet uptake was better than sodium selenite and their uptake by fibroblasts was not via an actively transport process. Sodium selenite induced a higher toxicity than SeMet. At 5 µM, sodium selenite inhibited cell proliferation associated with a blockage in the G2 phase and induced DNA fragmentation leading to caspase-3-dependent apoptosis cell death. At low doses (<1 µM), SeMet and sodium selenite induced glutathione peroxidase-1 (GPX1) activity and selenoproteinW1 (SEPW1) transcript expression but metalloproteinase (MMP)-1 was only induced by sodium selenite. SeMet and sodium selenite did not protect NHSFs from UVA-induced cell death. However, SeMet decreased malondialdehyde (MDA) and protected NHSFs from UVA-induced MMP1 and MMP3. We then observed a large difference in terms of photoprotection according to selenium forms. SeMet may be a potential agent for the prevention and treatment of skin photoageing.

Elements of margin of safety, toxicity and action of sodium selenite in a lipopolysaccharide rat model.

PROJECT: Both septic shock and sodium selenite (Na2SeO3) lead to multiple organ failure through oxidation. Na2SeO3 has direct oxidant effects above the nutritional level and indirect anti-oxidant properties. In a lipopolysaccharide (LPS) rat model we assessed margin of safety, toxicity and beneficial effect of pentahydrate Na2SeO3 (5H2O·Na2SeO3) at oxidant doses. PROCEDURE: In a three-step study on 204 rats we: (i) observed toxic effects of Na2SeO3 injected intraperitoneously (IP) and determined its Minimum Dose Without Toxic effect (MDWT) 0.25-0.35 mg/kg selenium (Se) content; (ii) injected IP LPS at 70% lethal dose (LD) followed, or not, one hour later by IP Na2SeO3 at MDWT and (iii) by doses>MDWT. At 48 h, in survivors, we measured plasma creatinine, lactate, aspartate and alanine aminotransferase (AST, ALT), nitric oxide (NO) and Se concentrations. RESULTS: (i) Na2SeO3 alone did not increase NO and lactate. Encephalopathy appeared at 1mg Se/kg. Creatinine increased at 1-1.75 mg Se/kg, AST, ALT at 3-4.5 mg Se/kg, and the minimum LD was 3 mg Se/kg. (ii) Mortality after LPS was 37/50 (74%, [62-86%]) vs. 20/30 (67%, [50-84%]) when followed by Na2SeO3 at MDWT (p=0.483) with a decreased in NO (-31%, p=0.038) a trend for lactate decrease (-19%, p=0.068) and an increased Se in plasma of survivals. (iii) All rats died at doses ≥0.6 mg/kg (p<0.001). CONCLUSION: Mechanisms of LPS and Na2SeO3 toxicity differ (i.e. NO, lactate). In septic shock 5H2O·Na2SeO3 toxicity increased, margin of safety decrease, but IP administration of dose considered as oxidant of 5H2O·Na2SeO3 showed beneficial effects.

Baseline plasma fatty acids profile and incident cardiovascular events in the SU.FOL.OM3 trial: the evidence revisited.

OBJECTIVE: We aimed to investigate the association between baseline plasma fatty acids profile and the risk of future major cardiovascular events in patients with a history of ischaemic heart disease or ischemic stroke. METHODS: Baseline plasma fatty acids as well as established cardiovascular risk factors were measured in 2,263 patients enrolled in the SUpplementation with FOLate, vitamins B-6 and B-12 and/or OMega-3 fatty acids randomized controlled trial. Incident major cardiovascular, cardiac and cerebrovascular events were ascertained during the 4.7 years of follow up. Hazard ratios were obtained from Cox proportional hazards models after adjustment for cardiovascular risk factors. RESULTS: During the follow-up, 154, 379 and 84 patients had major cardiovascular, cardiac and cerebrovascular events respectively. Upon adjustment for gender, initial event, baseline age and BMI, the risk of developing a major cardiovascular event decreased significantly in successive quartiles of arachidonic acid (P trend<0.002), total omega 3 polyunsaturated fatty acids (P trend<0.03), docosapentaenoic acid (P trend<0.019), docosahexaenoic acid (P trend<0.004), eicosapentaenoic acid + docosahexaenoic acid (P trend<0.03) and eicosapentaenoic acid + docosapentaenoic acid + docosahexaenoic acid (P trend<0.02). This inverse association was borderline significant with increased quartiles of stearidonic acid (P trend<0.06). In the full model, only stearidonic acid remained inversely associated with the risk of developing a major cardiovascular event (P trend<0.035), a cardiac event (P trend<0.016) or a cerebrovascular event (P trend<0.014), while arachidonic acid was inversely associated with the risk a cerebrovascular event (P trend<0.033). CONCLUSION: The inverse association of long chain omega 3 polyunsaturated fatty acids with recurrence of Cardiovascular diseases was mainly driven by well-known cardiovascular risk factors. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN41926726.

Prospective associations between plasma saturated, monounsaturated and polyunsaturated fatty acids and overall and breast cancer risk - modulation by antioxidants: a nested case-control study.

BACKGROUND: Mechanistic data suggest that different types of fatty acids play a role in carcinogenesis and that antioxidants may modulate this relationship but epidemiologic evidence is lacking. Our aim was to investigate the association between plasma saturated, monounsaturated and polyunsaturated fatty acids (SFAs, MUFAs and PUFAs) and overall and breast cancer risk and to evaluate the potential modulatory effect of an antioxidant supplementation on these relationships. METHODS: A nested case-control study included all first incident cancer cases diagnosed in the SU.VI.MAX study between 1994 and 2002 (n=250 cases, one matched control/case). Participants to the SU.VI.MAX randomized controlled trial received either vitamin/mineral antioxidants or placebo during this intervention period. Baseline fatty acid composition of plasma total lipids was measured by gas chromatography. Conditional logistic regression was performed overall and stratified by intervention group. RESULTS: Dihomo-γ-linolenic acid (Ptrend=0.002), the dihomo-γ-linolenic/linoleic acids ratio (Ptrend=0.001), mead acid (Ptrend=0.0004), and palmitoleic acid (Ptrend=0.02) were inversely associated with overall cancer risk. The arachidonic/dihomo-γ-linolenic acids ratio (Ptrend=0.02) and linoleic acid (Ptrend=0.02) were directly associated with overall cancer risk. Similar results were observed for breast cancer specifically. In stratified analyses, associations were only observed in the placebo group. Notably, total PUFAs were directly associated with overall (Ptrend=0.02) and breast cancer risk in the placebo group only. CONCLUSION: Specific SFAs, MUFAs and PUFAs were prospectively differentially associated with cancer risk. In addition, this study suggests that antioxidants may modulate these associations by counteracting the potential effects of these fatty acids on carcinogenesis.

Long-term selenium supplementation in HaCaT cells: importance of chemical form for antagonist (protective versus toxic) activities.

The beneficial effect of selenium (Se) on cancer is known to depend on the chemical form, the dose and the duration of the supplementation. The aim of this work was to explore long term antagonist (antioxidant versus toxic) effects of an inorganic (sodium selenite, Na2SeO3) and an organic (seleno-L-methionine, SeMet) forms in human immortalized keratinocytes HaCaT cells. HaCaT cells were supplemented with Na2SeO3 or SeMet at micromolar concentrations for 144 h, followed or not by UVA radiation. Se absorption, effects of UVA radiation, cell morphology, antioxidant profile, cell cycle processing, DNA fragmentation, cell death triggered and caspase-3 activity were determined. At non-toxic doses (10 µM SeMet and 1 µM Na2SeO3), SeMet was better absorbed than Na2SeO3. The protection of HaCaT from UVA-induced cell death was observed only with SeMet despite both forms increased glutathione peroxidase-1 (GPX1) activities and selenoprotein-1 (SEPW1) transcript expression. After UVA irradiation, malondialdehyde (MDA) and SH groups were not modulated whatever Se chemical form. At toxic doses (100 µM SeMet and 5 µM Na2SeO3), Na2SeO3 and SeMet inhibited cell proliferation associated with S-G2 blockage and DNA fragmentation leading to apoptosis caspase-3 dependant. SeMet only led to hydrogen peroxide production and to a decrease in mitochondrial transmembrane potential. Our study of the effects of selenium on HaCaT cells reaffirm the necessity to take into account the chemical form in experimental and intervention studies.

Dietary flavonoids increase plasma very long-chain (n-3) fatty acids in rats.

Flavonoids probably contribute to the health benefits associated with the consumption of fruit and vegetables. However, the mechanisms by which they exert their effects are not fully elucidated. PUFA of the (n-3) series also have health benefits. Epidemiological and clinical studies have suggested that wine flavonoids may interact with the metabolism of (n-3) PUFA and increase their blood and cell levels. The present studies in rats were designed to assess whether flavonoids actually increase plasma levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main very long-chain (n-3) PUFA. Rats were fed a corn-derived anthocyanin (ACN)-rich (ACN-rich) or ACN-free diet with constant intakes of plant and marine (n-3) PUFA for 8 wk (Expt. 1). Plasma fatty acids were measured by GC. The ACN-rich diet contained ~0.24 ± 0.01 mg of ACN/g pellets. There were no significant differences between groups in the main saturated, monounsaturated, and (n-6) fatty acids. In contrast, plasma EPA and DHA were greater in the ACN-rich diet group than in the ACN-free diet group (P < 0.05). We obtained similar results in 2 subsequent experiments in which rats were administered palm oil (80 µL/d) and consumed the ACN-rich or ACN-free diet (Expt. 2) or were supplemented with fish oil (60 mg/d, providing 35 mg DHA and 12 mg EPA) and consumed the ACN-rich or ACN-free diet (Expt. 3). In both experiments, plasma EPA and DHA were significantly greater in the ACN-rich diet group. These studies demonstrate that the consumption of flavonoids increases plasma very long-chain (n-3) PUFA levels. These data confirm previous clinical and epidemiological studies and provide new insights into the health benefits of flavonoids.

Protective effect of dietary n-3 polyunsaturated fatty acids on myocardial resistance to ischemia-reperfusion injury in rats.

Dietary n-3 polyunsaturated fatty acids (PUFA) reduce coronary heart disease (CHD) complications, such as chronic arrhythmia and sudden cardiac death. Improved myocardial resistance to ischemia-reperfusion injury results in smaller myocardial infarction, which is a major factor in the occurrence of CHD complications. We hypothesized that a specific dietary fatty acid profile (low in saturated and n-6 PUFA but high in plant and marine n-3 PUFA) may improve myocardial resistance to ischemia-reperfusion injury and reduce infarct size. To test this assumption, we used a well-defined rat model of myocardial infarction. Based on our results, in comparison to a diet that is high in either saturated or n-6 PUFA but poor in plant and marine n-3 PUFA, a diet that is low in saturated fats and n-6 PUFA but rich in plant and marine n-3 PUFA results in smaller myocardial infarct size (P < .01). The effects of the 3 diets were also examined by analyzing the fatty acid composition of plasma, erythrocyte cell membranes, and the phospholipids of myocardial mitochondria. The results show a great accumulation of n-3 PUFA and a parallel decrease in arachidonic acid, the main n-6 PUFA, in plasma, cell membranes, and cardiac mitochondria (P < .0001). We conclude that improved myocardial resistance to ischemia-reperfusion may be one of the critical factors explaining the protective effects of dietary n-3 PUFA against CHD complications in humans. In addition to increasing n-3 PUFA intake, an optimal dietary pattern aimed at reducing cardiovascular mortality should include a reduction of the intake of both saturated and n-6 PUFA.

Chromium III histidinate exposure modulates gene expression in HaCaT human keratinocytes exposed to oxidative stress.

While the toxicity of hexavalent chromium is well established, trivalent chromium is an essential nutrient involved in insulin and glucose homeostasis. To study the antioxidant effects of Cr(III)His, cDNA arrays were used to investigate the modulation of gene expression by trivalent chromium histidinate (Cr(III)His) in HaCaT human keratinocytes submitted to hydrogen peroxide (H2O2). Array was composed by a set of 81 expressed sequences tags (ESTs) essentially represented by antioxidant and DNA repair genes. HaCaT were preincubated for 24 h with 50 microM Cr(III)His and were treated with 50 muM H2O2. Total RNAs were isolated immediately or 6 h after the stress. In Cr(III)His preincubated cells, transcripts related to antioxidant family were upregulated (glutathione synthetase, heme oxygenase 2, peroxiredoxin 4). In Cr(III)His preincubated cells and exposed to H2O2, increased expressions of polymerase delta 2 and antioxidant transcripts were observed. Biochemical methods performed in parallel to measure oxidative stress in cells showed that Cr(III)His supplementation before H2O2 stress protected HaCaT from thiol groups decrease and thiobarbituric acid reactive substances increase. In summary, these results give evidence of antioxidant gene expression and antioxidant protection in HaCaT preincubated with Cr(III)His and help to explain the lack of toxicity reported for Cr(III)His.

Zinc supplementation does not alter plasma homocysteine, vitamin B12 and red blood cell folate concentrations in French elderly subjects.

BACKGROUND/AIMS: In ageing, low folates and vitamin B12 status are frequent and can explain the increase of plasma homocysteine level. Zinc is involved in the folates and vitamin B12 metabolism with opposite actions. The aim of this study was to investigate the effects of zinc supplementation on homocysteine and vitamin B12 plasma levels as well as red blood cell folate level in French ageing subjects participating in the ZENITH study. METHODS: Apparently healthy middle-aged (55-70 years) and free-living older (70-85 years) subjects were enrolled. They were randomly allocated to three groups: 0, 15 or 30 mg Zn per day for 6 months as zinc gluconate in addition to their usual dietary intake. RESULTS: At baseline, plasma homocysteine levels (15.2+/-3.5 micromol/L) in older people were higher than in the middle-aged subjects (12.7+/-2.7 micromol/L) and was negatively correlated with vitamin B12 values (p=0.0036, r=-0.215) and with RBC folate levels (p<0.0001, r=-0.30). These results are in agreement with previous data. However, we found no correlation between the biomarkers of zinc status and homocysteine, vitamin B12 or folate levels at baseline. Moreover, 6-month zinc supplementation did not modify homocysteine, vitamin B12 and RBC folate values in either of the groups. CONCLUSIONS: Zinc supplementation at moderate doses do not lead to deleterious effect on folate or vitamin B12 status in ageing healthy free-living people, but does not have any beneficial effects on homocysteine metabolism either.

Acacia salicina extracts protect against DNA damage and mutagenesis in bacteria and human lymphoblast cell K562 cultures.

Three extracts were prepared from the leaves of Acacia salicina: aqueous, methanol, and ethyl acetate extracts. The antigenotoxic properties of these extracts were investigated by assessing the inhibition of mutagenicity of the indirect-acting mutagen benzo[a]pyrene using the Ames assay and the genotoxicity of the direct-acting mutagen, hydrogen peroxide, using the "Comet assay." Aqueous, methanol, and ethyl acetate extracts at doses of 500, 50, and 500 microg per plate reduced benzo[a]pyrene mutagenicity by 95%, 82%, and 40%, respectively, in Salmonella typhimurium TA98 strain and by 91%, 66% and 63%, respectively, at the same doses with a TA97 assay system. Human lymphoblast cells K562 were pretreated with 50% inhibition concentration of each extracts and then treated by H(2)O(2), for the Comet assay. The Comet assay results showed that ethyl acetate and methanol extracts decreased the DNA damage caused by H(2)O(2) by, respectively, 34.8% and 31.3%. We envisaged also the study of the antioxidant effect of these extracts by the enzymatic xanthine/xanthine oxidase assay. Results indicated that methanol and ethyl acetate extracts were potent inhibitors of xanthine oxidase and superoxide anion scavengers. We conclude that these integrated approaches to antigenotoxicity and antioxidant assessment may be useful to help compare the beneficial effects associated with using A salicina as medicinal and dietary plant.

Antimutagenic, antigenotoxic and antioxidant activities of Acacia salicina extracts (ASE) and modulation of cell gene expression by H2O2 and ASE treatment.

The total oligomers flavonoids (TOF), chloroform, petroleum ether and aqueous extracts from Acacia salicina, were investigated for the antioxidative, cytotoxic, antimutagenic and antigenotoxic activities. The viability of K562 cells were affected by all extracts after 48 h exposure. Our results showed that A. salicina extracts have antigenotoxic and/or antimutagenic activities. TOF and chloroform extracts exhibit antioxidant properties, expressed by the capacity of these extracts to inhibit xanthine oxidase activity. To further explore the mechanism of action of A. salicina extracts, we characterized expression profiles of genes involved in antioxidant protection and DNA repair in the human lymphoblastic cell line K562 exposed to H2O2. Transcription of several genes related to the thioredoxin antioxidant system and to the DNA base-excision repair pathway was up-regulated after incubation with chloroform, TOF and petroleum ether extracts. Moreover genes involved in the nucleotide-excision repair pathway and genes coding for catalase and Mn-superoxide-dismutase, two important antioxidant enzymes, were induced after incubation with the chloroform extract. Taken together, these observations provide evidence that the chloroform and TOF extracts of A. salicina leaves contain bioactive compounds that are able to protect cells against the consequences of an oxidative stress.

Interactions of ethanol drinking with n-3 fatty acids in rats: potential consequences for the cardiovascular system.

Moderate ethanol drinking (ED) and n-3 fatty acids have both been associated with low cardiac mortality. However, there are few data evaluating the interactions of ED with n-3. We recently reported that moderate ED results in increased n-3 in cardiac patients. The main aim of the present study was, through a well-controlled experimental model, to confirm that chronic ED actually results in increased n-3. Secondary aims were to examine the effects of chronic ED on cardiac mitochondria, cardiac function and experimental myocardial infarction. We studied the fatty acid profiles of plasma, cell membranes and cardiac mitochondria phospholipids in a rat model of chronic ED. In plasma and cell membranes, ED actually resulted in higher n-3 (P = 0.005). In mitochondria phospholipids of ED rats, n-3 were also increased (P < 0.05) but quite modestly. Cardiac mitochondrial function and left ventricular function were not significantly different in ED and control rats, while infarct size after 30 min ischaemia and reperfusion was smaller (P < 0.0001) in ED rats. This is the first animal study confirming interaction of alcohol drinking with n-3. We found no harmful effect of chronic ED on the heart in that model but a significant cardioprotection. Further studies are warranted to investigate the mechanisms by which moderate ED alters the metabolism of n-3 and whether n-3 are the mediators of the ED-induced cardioprotection.

Transcriptional response of genes involved in cell defense system in human cells stressed by H2O2 and pre-treated with (Tunisian) Rhamnus alaternus extracts: combination with polyphenolic compounds and classic in vitro assays.

The ability of three Rhamnus alaternus leaves extracts on antigenotoxic and gene expression level effects was respectively investigated in a bacterial assay system, i.e. the SOS chromotest with Escherichia coli PQ37 and in human K562 lymphoblast cell line. Total oligomers flavonoids (TOF) enriched, methanol and ethyl acetate extracts were prepared from powdered R. alaternus leaves and characterized quantitatively for the presence of polyphenolic compounds. We explored the response to oxidative stress using the transcriptional profile of genes in K562 cells stressed with H2O2 after incubation with plant extracts. For this purpose, we used a cDNA microarrays containing 82 genes related to cell defense, essentially represented by antioxidant and DNA repair genes. Analysis revealed that SOD1, AOE 372, TXN genes involved in the antioxidant defense system and XPC, LIG4, POLD2, PCNA genes implied in the DNA repair system were among the most expressed ones in the presence of the tested extracts. These results were in accordance with those obtained when we tested the antigenotoxic and antioxidant effects of the same extracts with, respectively the SOS chromotest and the xanthine/xanthine oxidase enzymatic assay system. The effect of the tested extracts on SOS response induced by both Aflatoxin B1 (AFB1: 10 microg/assay) and nifuroxazide (20 microg/assay) showed that the TOF extract exhibited the highest antimutagenic level towards the indirect mutagen AFB1. Whereas ethyl acetate extract showed the highest antimutagenic effect towards the direct mutagen, nifuroxazide. None of the tested extracts induced mutagenic activity. However all the tested extracts exhibited xanthine oxidase inhibiting and superoxide anions scavenging effects. R. alaternus extracts contain compounds with significant antioxidant and antigenotoxic activities. These compounds modulate gene expression as detected by using cDNA arrays.

Biologically active oxidized lipids (phytoprostanes) in the plant diet and parenteral lipid nutrition.

Phytoprostanes (PP) are autoxidation products of alpha-linolenate that are present in all plant tissues. Several classes of PP with a prostaglandin (PG) F1-, E1-, A1- and B1-like structure were identified and quantified by gas chromatography-mass spectrometry in vegetable oils and parenteral nutrition (intralipid). High levels of PP (0.09 up to 99 mg/l) were found even in apparently fresh vegetable oils. After oral consumption of olive or soybean oil, PPF1 were absorbed, found to circulate in plasma in conjugated form and excreted in free form into urine. Evidence is emerging that certain PP, such as the PPE1, may modulate the function of immune cells in a PG-like fashion. Here, we show that PPA1- and deoxy-PPJ1 display potent anti-inflammatory and apoptosis inducing activities similar to PGA1 and deoxy-PGJ2. Results of this study indicate that PP are novel, biologically active lipids in plant nutrition.