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Changes in ether-linked phospholipids in rat kidney by dietary alpha-linolenic acid in vivo.

We investigated the effects of perilla oil containing a high level of alpha-linolenic acid on in vivo phospholipid metabolism, particularly three subclasses of choline glycerophospholipids (CGP) and ethanolamine glycerophospholipids (EGP), in rat kidney. After three weeks of feeding, a significantly lower proportion (by 35%) of the alkylacyl subclass of CGP was found in the perilla oil, as compared to corn oil-fed animals. The alkylacyl species of EGP was also higher in the perilla oil than in the corn oil-fed animals. These alterations were accompanied by a remarkably lower proportion of arachidonic acid and a higher level of eicosapentaenoic acid (EPA) in all six subclasses of CGP and EGP in the perilla oil-fed animals. The levels of linoleic acid were even higher in the diacyl subclasses of CGP and EGP in the perilla oil group, suggesting that desaturase and elongase enzymes prefer n-3 to n-6 fatty acids as substrates for diacyl species. These data are useful in defining the effects of alpha-linolenic acid on the biosynthesis of renal phospholipids and on the replacement of n-6 with n-3 fatty acids in the six CGP and EGP subclasses.

Animals↗

Dietary alpha-linolenate/linoleate balance influences learning and memory in the senescence-accelerated mouse (SAM).

The senescence-accelerated mouse (SAMP8) is a model of age-related deterioration of memory and learning ability. A semipurified diet supplemented either with safflower oil (rich in linoleate) or with perilla oil (rich in alpha-linolenate) was fed to SAMP8 mouse dams and their pups. The offspring (males from several mothers) at 28 weeks of age were used for behavioral tests. The proportions of n-3 and n-6 highly unsaturated fatty acids in brain phospholipids reflected the n-3/n-6 balance of the diets. The learning and memory abilities of the two dietary groups were tested with the Sidman active avoidance task and the light and dark discrimination learning test. The group given perilla oil showed much greater improvement in learning in the Sidman active avoidance task than did the group fed safflower oil. In the light and dark discrimination learning test, the total number of responses to positive and negative stimuli was lower in those fed perilla oil, and their responses to positive stimuli were higher than to negative stimuli after the 10th session. Consequently, the correct response ratios of discrimination were higher in the perilla oil group than in the safflower oil group. In the open field test, the total amount of locomotor activity during 5 min was lower in the perilla oil group at 7 months of age than in the group fed safflower oil.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Activity of hepatic fatty acid oxidation enzymes in rats fed alpha-linolenic acid.

The activity of hepatic fatty acid oxidation enzymes in rats fed linseed and perilla oils rich in alpha-linolenic acid (alpha-18:3) was compared to that in rats fed safflower oil rich in linoleic acid (18:2) and a saturated fat (palm oil). Palm and safflower oils were essentially devoid of alpha-18:3. The palmitoyl-CoA oxidation rates both in mitochondrial and peroxisomal pathways in liver homogenates were significantly higher in rats fed linseed oil than in those fed palm and safflower oils. Among rats fed diets containing palm oil, safflower oil, fat mixtures composed of safflower and perilla oils (2:1, w/w and 1:2, w/w), and perilla oil, mitochondrial and peroxisomal fatty oxidation rates increased with increasing dietary levels of perilla oil. Compared to palm and safflower oils, dietary alpha-18:3 either in the form of linseed or perilla oils profoundly increased the activity of carnitine palmitoyltransferase, acyl-CoA oxidase, 3-ketoacyl-CoA thiolase, and 2,4-dienoyl-CoA reductase. Smaller but significant increases by dietary alpha-18:3 of the activity of acyl-CoA dehydrogenase, enoyl-CoA hydratase, and delta 3, delta 2-enoyl-CoA isomerase were also observed. Unexpectedly, dietary alpha-18:3 greatly reduced the activity of 3-hydroxy-acyl-CoA dehydrogenase. Compared to palm oil, dietary polyunsaturated fats significantly reduced the activity of fatty acid synthetase and glucose-6-phosphate dehydrogenase to the same levels. The activity of pyruvate kinase was significantly higher in rats fed palm oil than in those fed polyunsaturated fats. The extent of reduction was more prominent with polyunsaturated fats containing alpha-18:3 than with safflower oil devoid of alpha-18:3. Thus, compared to linoleic acid and saturated fatty acids, dietary alpha-18:3 caused characteristic changes in the activity of hepatic enzymes in fatty acid and glucose metabolism in rats.

Adipose Tissue, Brown↗

Effects of dietary supplementation with n-3 fatty acids compared with n-6 fatty acids on bronchial asthma.

OBJECTIVE: The effects of perilla seed oil (n-3 fatty acids) on bronchial asthma were compared with the effects of corn oil (n-6 fatty acids) in relation to the pulmonary function and the generation of leukotriene B4 (LTB4) and C4 (LTC4) by leucocytes. METHODS AND SUBJECTS: 14 asthmatic subjects were divided randomly into two groups: one group (7 subjects) consumed perilla seed oil-rich supplementation and the other group (7 subjects) consumed corn oil-rich supplementation for 4 weeks. Generation of LTs by leucocytes and respiratory function were compared between the two groups. RESULTS: The generation of LTB4 and LTC4 by leucocytes tended to increase in subjects (N=7) with corn oil-rich supplementation, and decrease in subjects (N=7) with perilla seed oil-rich supplementation. Significant differences between the two groups were observed in the generation of LTB4 at 2 weeks (p<0.05) and LTC4 at 2 weeks (p<0.05) after dietary supplementation. Significant increases in the value of PEF (p<0.05), FVC (p<0.01), FEV(1.0) (p<0.05) and V(25) (p<0.05) were found in subjects who received perilla seed oil supplementation for 4 weeks. And significant differences in the value of FVC (p<0.05) and FEV(1.0) (p<0.05) were observed between the two groups after 4 weeks of dietary supplementation. CONCLUSION: These results suggest that perilla seed oil-rich supplementation is useful for the treatment of asthma in terms of suppression of LTB4 and LTC4 generation by leucocytes, and improvement of pulmonary function.

Adult↗

Effect of a high linoleate and a high alpha-linolenate diet on general behavior and drug sensitivity in mice.

Semi-purified diets supplemented with either a high linoleate (n-6) (safflower) oil or a high alpha-linolenate (n-3) (perilla) oil were fed to mouse mothers and their offspring through 6 weeks of age. The proportions of n-3 and n-6 highly unsaturated fatty acids in brain phospholipids reflected the n-3/n-6 balance of the diets while no difference was found in phospholipid compositions or cholesterol/phospholipid ratios. In the elevated plus maze task, the total number of entries into the open- and enclosed-arms was smaller and the time spent in the dark enclosed arms tended to be longer in the perilla group than the safflower group. The time required to reach a safe platform in Morris's water maze test was less in the perilla group, but no significant difference was observed in the entries into the arms darkened with a movable cover in Y-maze dark-preference task. The safflower group was more sensitive to pentobarbital; the anesthesia onset time was less and the anesthetic time was longer than in the perilla group. Increased locomotion induced by scopolamine injection was less in the safflower group as compared with the perilla group. These results indicate that in mice the dietary alpha-linolenate/linoleate balance affects the n-3/n-6 ratio of brain phospholipid acyl chains and that this is accompanied by general behavioral changes as well as changes in sensitivities to drugs known to affect behavior.

Analgesia↗

Dietary alpha-linolenic acid lowers postprandial lipid levels with increase of eicosapentaenoic and docosahexaenoic acid contents in rat hepatic membrane.

This study was designed to examine the effects of dietary n-3 and n-6 polyunsaturated fatty acids (PUFA) on postprandial lipid levels and fatty acid composition of hepatic membranes. Male Sprague-Dawley rats were trained for a 3-h feeding protocol and fed one of five semipurified diets: one fat-free diet or one of four diets supplemented with 10% (by weight) each of corn oil, beef tallow, perilla oil, and fish oil. Two separate experiments were performed, 4-wk long-term and 4-d short-term feeding models, to compare the effects of feeding periods. Postprandial plasma lipid was affected by dietary fats. Triacylglycerol (TG) and total cholesterol levels were decreased in rats fed perilla oil and fish oil diets compared with corn oil and beef tallow diets. Hepatic TG and total cholesterol levels were also reduced by fish oil and perilla oil diets. Fatty acid composition of hepatic microsomal fraction reflected dietary fatty acids and their metabolic conversion. The major fatty acids of rats fed the beef tallow diet were palmitic, stearic, and oleic. Similarly, linoleic acid (LA) and arachidonic acid in the corn oil group, alpha-linolenic acid (ALA) and eicosapentaenoic acid (EPA) in the perilla oil group, and palmitic acid and docosahexaenoic acid (DHA) in the fish oil group were detected in high proportions. Both long- and short-term feeding experiments showed similar results. In addition, microsomal DHA content was negatively correlated with plasma lipid levels. Hepatic lipid levels were also negatively correlated with EPA and DHA contents. These results suggest that n-3 ALA has more of a hypolipidemic effect than n-6 LA and that the hypolipidemic effect of n-3 PUFA may be partly related to the increase of EPA and DHA in hepatic membrane.

Animals↗

Effect of dietary alpha-linolenate/linoleate balance on mean survival time, incidence of stroke and blood pressure of spontaneously hypertensive rats.

Following the suckling period, stroke-prone spontaneously hypertensive rats (SHR-SP) were fed semi-purified diets supplemented either with safflower seed oil (rich in linoleic acid) or with perilla seed oil (rich in alpha-linolenic acid). The mean survival time of male SHR-SP fed the perilla diet was longer than that fed the safflower diet by 17% (p less than 0.001) while the difference was 15% in female SHR-SP (p less than 0.05). The mean survival times of female SHR-SP were more than 40% longer than those of male SHR-SP in both dietary groups. Post-mortem examinations of brains revealed apoplexy-related symptoms as the major cause of the death in both dietary groups. The systolic blood pressure was lower by ca. 10% (21 mmHg) in the perilla group than in both the safflower group and conventional diet group. The eicosapentaenoate (20:5 n-3)/arachidonate (20:4 n-6) ratio of platelet phospholipids in spontaneously hypertensive rat (SHR), a measure of platelet aggregability, was much higher in the perilla group than in the safflower group. Thus, increasing the dietary alpha-linolenate/linoleate ratio resulted in an increased mean survival time of SHR-SP rats, possibly by lowering blood pressure and platelet aggregability.

Animals↗

Effects of cooking plant oils on recurrent aphthous stomatitis: a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: One-third of the total population seems to develop minor recurrent aphthous stomatitis (RAS) during their lifetime. However, well-controlled dietary intervention studies to prevent minor RAS are very rare. The objective of the present study was to investigate whether the prevalence of RAS decreased with perilla oil (rich in alpha-linolenic acid). METHODS: Thirty subjects (8 men and 22 women) who had minor RAS at least once a month were randomly allocated to a soybean oil group or a perilla oil group in a double-blind manner (experimental phase) after a run-in phase of 4 mo during which subjects used a reference oil, the most popular cooking oil in Japan, or a 50/50 mixture of soybean oil and rapeseed oil. During the experimental phase, subjects were asked to use soybean oil or perilla oil as the sole cooking oil for 8 mo. Blood samples were collected at the start and end of the experimental phase for fatty acid analysis of total plasma phospholipid fraction. Occurrence and needed days for healing of minor RAS were recorded during the two phases and compared. RESULTS: alpha-Linolenic acid concentrations in the plasma phospholipid fraction increased significantly in both groups during the experimental phase to a similar extent. The prevalence of minor RAS in the experimental phase decreased significantly in both groups compared with the run-in phase to a similar extent, without intergroup differences. CONCLUSION: Perilla oil, which is rich in alpha-linolenic acid, was not superior to soybean oil in preventing minor RAS. There was a possibility that avoiding rapeseed oil might be beneficial for prevention of minor RAS.

Adult↗

Effects of n-3 polyunsaturated fatty acids on indomethacin-induced changes in eicosanoid production and blood flow in the gastric mucosa of rats.

We investigated the effects of n-3 polyunsaturated fatty acids (PUFAs) on non-steroidal anti-inflammatory drug (NSAID)-induced changes in microcirculation and eicosanoid production in the gastrointestinal mucosa. We measured gastric mucosal blood flow using laser Doppler flowmetry, assessed the fatty acid composition in the mucosal phospholipids, and quantified the production of prostaglandin E2 (PGE2), leukotriene B4, and leukotriene C4 (LTB4 and C4) from the mucosa with the stimulation of calcium ionophore 20 min after an injection of indomethacin or vehicle in rats fed a diet containing different compositions of alpha-linolenic acid. Four weeks after the initiation of the test diet the arachidonic acid level in gastric mucosal phospholipids was significantly lower in the perilla group than in the other three groups. Conversely, alpha-linolenic acid and eicosapentaenoic acid (EPA) were significantly higher in the perilla group than in the other three groups. The percent of gastric mucosal blood flow in the three groups administered indomethacin were significantly lower than that in the control group injected with vehicle alone. The percent of gastric mucosal blood flow in the perilla group was significantly higher than that in the corn group. LTB4 and LTC4 production from the gastric mucosa in the soybean and corn groups were significantly higher than those in the control group, and the LTC4 production in the perilla group was significantly lower than that in the corn group. There were no significant differences in PGE2 production among the four groups. Our results suggest that alpha-linolenic acid affectively suppressed the indomethacin-induced decreases in gastric mucosal blood flow by increasing EPA and decreasing the levels of arachidonic acid and LTC4 in the gastric mucosa.

Animals↗

Effect of dietary linoleate/alpha-linolenate balance on experimentally induced gastric injury in rats.

Rats were fed diets containing different ratios of linoleate (18:2 n-6) to alpha-linolenate (18:3 n-3), and the severity of gastric injury induced by ethanol, ischemia/reperfusion and water-immersion stress was compared. On decreasing the 18:2 n-6/18:3 n-3 ratios in the diets, the proportion of arachidonic acid (20:4 n-6) decreased and that of eicosapentaenoic acid (20:5 n-3) increased in the phospholipids of the gastric mucosa, which was associated with decreased mucosal prostaglandin E2 content. Mucosal injury in all the three experimental models was exacerbated significantly in the diet group fed 18:2 n-6/18:3 n-3 ratio of 0.25 (perilla oil) as compared with the groups fed dietary oils with 18:2 n-6/18:3 n-3 ratios of 2.7 (mixture of perilla and safflower oils) and 127 (safflower oil). This adverse effect induced by perilla oil diet was not observed when rats were pretreated with a mild irritant (20% ethanol) prior to challenge with a strong irritant (absolute ethanol). Furthermore, an 18:2 n-6/18:3 n-3 ratio of as low as 1 was found to be in a safe range in the water-immersion stress ulcer model. Thus, oils with very low n-6/n-3 ratios, for example perilla oil, could be used without the risk of the observed adverse effects on experimental gastric injury in people of industrialized countries ingesting foods with n-6/n-3 ratios of above 4. A decrease in the n-6/n-3 ratios to 2 or below is still recommended for the prevention of chronic diseases in the elderly related to atherosclerosis and inflammation.

Animals↗

Functional changes of rat brain microsomal membrane surface after learning task depending on dietary fatty acids.

Biochemical characteristics of brain microsomal membranes were examined before and after the brightness-discrimination learning tasks in rats that were fed either safflower oil (alpha-linolenate-deficient) or perilla oil (alpha-linolenate-sufficient) diets. We detected small changes in the chain elongation system for polyunsaturated fatty acids in microsomes, whereas no significant difference was detected in the inositol trisphosphate-induced calcium release and ATP-induced calcium uptake profiles of microsomes between the two dietary groups. The calcium ion-induced aggregation rate of microsomes was determined in both groups. We found that the aggregation rate of microsomes in the safflower oil group was significantly greater than that in the perilla oil group. The difference in susceptibility of microsomal membrane phospholipids to phospholipase A2 between the groups was obvious, and the amount of released fatty acids by phospholipase A2 from the perilla oil group microsomes was nearly half of that from the safflower oil group microsomes after the learning task. Susceptibility of sialic acids on the brain microsomal membranes to exogenous sialidase was different only after the learning task in the safflower and perilla oil groups. These results suggest that the biochemical characteristics of membrane surfaces of brain microsomes are affected significantly by the learning task itself in a dietary oil-dependent manner.

Animals↗

Linoleic and alpha-linolenic acids differently modify the effects of elaidic acid on polyunsaturated fatty acid metabolism and some immune indices in rats.

To explore whether the metabolic responses to trans, compared with cis, fatty acids depend on the source of dietary polyunsaturated fatty acids (PUFA), male Sprague-Dawley rats, 5 weeks old, were fed on diets containing 30 g oleic (cis) or elaidic (trans) acids/kg in combination with either 70 g perilla oil (alpha-linolenic acid) or safflowerseed oil (linoleic acid)/kg for 3 weeks in separate experiments. The dietary fats were adjusted to have the same level of total PUFA. The dietary manipulation did not influence the growth indices, but spleen weight was greater when the dietary PUFA source was perilla oil. The incorporation of trans fatty acid into liver phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine and adipose tissue lipids, particularly phospholipids, was significantly higher when rats were fed on safflowerseed oil compared with perilla oil. However, only limited differences were observed in the effects of cis and trans fatty acids on the proportions of PUFA in liver phospholipids. Splenic production of prostaglandin E2 was reduced by trans fatty acid when safflowerseed oil was the PUFA source, but no trans effect was observed on leukotriene C4 production. Dietary PUFA significantly influenced the concentration of plasma immunoglobulins (Ig) but the effect of geometry was only seen in IgG which was increased by trans acid. Dietary trans fatty acid increased the CD4+:CD8+ T-lymphocyte ratio in the spleen, reflecting a decreasing trend of the proportion of CD8+, when combined with perilla oil. These observations indicate that the type of PUFA simultaneously ingested specifically influences the effect that trans acid exerts on PUFA metabolism, eicosanoid production and some immune indices.

Animals↗

Induction of tumors in the colon and liver of the immunodeficient (SCID) mouse by 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ)-modulation by long-chain fatty acids.

We have recently shown that immunodeficient (SCID) mice, which lack functional T and B cells, are highly susceptible to low dose site specific induction of colon aberrant crypt foci (ACF), surrogates for colon tumors, by 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ). To test whether long-term exposure to a high dose in the diet might prove carcinogenic to the SCID mouse colon, in contrast to other mice strains tested to date, the compound was administered at 300 p.p.m. in the diet to female 6-7-week-old SCID mice for 32 weeks. IQ induced high numbers of ACF, hyperplastic polyps, dysplasia, and colon adenomas, as well as hepatocellular altered foci and liver adenomas. Induction of colon tumors did not correlate with the main sites where ACF developed, the proximal colon, however, being seen mainly in the mid and distal colon. Induction of colon tumors correlated significantly with the incidence of dysplasia, crypt height, the mitotic index, cell proliferation and numbers of 8-hydroxydeoxyguanosine (8-OHdG)-positive cells in the colon crypt, particularly in mid and distal colon. Administration of 20% omega-6 polyunsaturated fatty acids (corn oil), omega-3 polyunsaturated fatty acids (perilla oil), or monounsaturated fatty acids (olive oil) simultaneously with IQ in the diet resulted in: (i) inhibition of colon and liver tumor induction by corn and perilla oil, whereas olive oil showed no effects; (ii) no reduction in total numbers of ACF by corn oil or perilla oil but significant suppression in the olive oil treated group; (iii) inhibition of tumor development particularly by omega-3 polyunsaturated fatty acids in perilla oil, correlating significantly with decreased cell proliferation in both colon and liver and a marked decrease in crypt heights and mitotic indices. Selective reduction in the numbers of 8-OHdG-positive nuclei, mainly in the middle and distal colon crypts, was also found to correlate with tumor inhibition. Thus, the results indicate carcinogenicity of IQ in the colon of the SCID mouse and preventive effects of polyunsaturated fatty acids.

8-Hydroxy-2'-Deoxyguanosine↗

High-linoleate and high-alpha-linolenate diets affect learning ability and natural behavior in SAMR1 mice.

Semipurified diets incorporating either perilla oil [high in alpha-linolenate, 18:3(n-3)] or safflower oil [high in linoleate, 18:2(n-6)] were fed to senescence-resistant SAMR1 mouse dams and their pups. Male offspring at 15 mo were examined using behavioral tests. In the open field test, locomotor activity during a 5-min period was significantly higher in the safflower oil group than in the perilla oil group. Observations of the circadian rhythm (48 h) of spontaneous motor activity indicated that the safflower oil group was more active than the perilla oil group during the first and second dark periods. The total number of responses to positive and negative stimuli was higher in the safflower oil group than in the perilla oil group in the light and dark discrimination learning test, but the correct response ratio was lower in the safflower oil group. The difference in the (n-6)/(n-3) ratios of the diets reflected the proportions of (n-6) polyunsaturated fatty acids, rather than those of (n-3) polyunsaturated fatty acids in the brain total fatty acids, and in the proportions of (n-6) and (n-3) polyunsaturated fatty acids in the total polyunsaturated fatty acids of the brain phospholipids. These results suggest that in SAMR1 mice, the dietary alpha-linolenate/linoleate balance affects the (n-6)/(n-3) ratio of brain phospholipids, and this may modify emotional reactivity and learning ability.

Aging↗

Effect of a high alpha-linolenate and high linoleate diet on membrane-associated enzyme activities in rat brain--modulation of Na+, K+- ATPase activity at suboptimal concentrations of ATP.

Semi-purified diets supplemented with either a high alpha-linolenate (n - 3) (perilla) oil or a high linoleate (n - 6) (safflower) oil were fed to rats through two generations. Rats fed safflower oil showed a decrease in docosahexaenoic acid (n - 3) and a compensatory increase in docosapentaenoic acid (n - 6) in all the brain regions and organelles examined, when compared with rats fed perilla oil. As reported previously, the safflower oil-fed rats exhibited inferior learning ability compared with the perilla oil-fed rats (N. Yamamoto et al., J. Lipid Res. 28, 144 (1987)). Using brains of rats in these dietary groups, the activities of several enzymes, Na+ , K+-ATPase, Ca2+-ATPase, 5'-nucleotidase, 2',3'-cyclic nucleotide phosphodiesterase, acetylcholinesterase, and choline acetyltransferase in membranes, were compared. The 5'-nucleotidase activity in cortex and hippocampus, and the Na+, K+-ATPase activity in myelin decreased slightly but significantly in the safflower oil group. None of the other membrane-associated enzyme activities in all the brain regions and organelles examined was affected significantly by the dietary fatty acids under optimal assay conditions in vitro. However, in the safflower oil group, the Na+, K+-ATPase activity of synaptosomes at a suboptimal concentration of ATP was 78% that in the perilla oil group. These results suggest that relatively large changes in the proportions of n - 3 and n - 6 polyunsaturated fatty acids in brain membranes caused by dietary manipulation do not provoke significant alterations in most membrane-bound enzyme activities. However, a small but significant change in Na+, K+-ATPase activity at a suboptimal concentration of ATP may be implicated in the altered learning behavior reported earlier.

Adenosine Triphosphate↗

Effects of dietary vegetable oils on behavior and drug responses in mice.

Previously, we noted significant differences in the behavioral patterns of mice fed safflower oil with a very low alpha-linolenate/linoleate ratio and perilla oil with a high alpha-linolenate/linoleate ratio from mothers to offsprings. In this report, we compared the behavior and drug responses in mice fed diets containing six different vegetable oils-corn, rapeseed, soybean, safflower, perilla and a mixture of perilla and safflower oils- for a relatively short period: 8 months after weaning. Soybean oil is a component of most conventional diets and was used as a control. The alpha-linolenate/linoleate ratios of the oils appeared to affect the locomotor activities in a wheel cage: the activity decreased in the order of safflower, the mixture (1:1) and the perilla oil groups. However, the rapeseed oil group exhibited much higher locomotor activity than that expected from the alpha-linolenate/linoleate ratio. Additionally, the rapeseed oil group exhibited unusual behavior patterns, including higher ambulation and rearing activities, faster acquisition of the water maze task and slower habituation behavior as compared with the control group. Susceptibility to pentobarbital anesthesia tended to be higher in the rapeseed oil group. The differences in the alpha-linolenate/linoleate ratios of these oils alone do not account for the observed differences in the behavioral patterns among the six dietary groups. Although we cannot exclude the possibility that the observed behavioral anomaly is due to the unique fatty acid composition of rapeseed oil, we speculate that a factor(s) other than fatty acids in rapeseed oil affected nervous system functions.

Analgesics↗

Effect of replacing a high linoleate oil with a low linoleate, high alpha-linolenate oil, as compared with supplementing EPA or DHA, on reducing lipid mediator production in rat polymorphonuclear leukocytes.

The fatty acid composition of rat polymorphonuclear leukocytes (PMN) was modified by diets supplemented with a high linoleate (LA) safflower oil (76% LA), mixtures of eicosapentaenoate (EPA) and safflower oil (EPA(20) containing 20% EPA and 61% LA, EPA(40) containing 40% EPA and 46% LA), mixtures of docosahexaenoate (DHA) and safflower oil (DHA(20) containing 20% DHA and 61% LA, DHA(40) containing 40% DHA and 46% LA) or a high alpha-linolenate (alpha-LNA) perilla oil (57% alpha-LNA and 13% LA), and then lipid mediator production in casein-induced peritoneal PMN were compared. EPA and DHA were relatively ineffective in reducing platelet-activating factor (PAF) production; a statistically significant reduction was observed only in the DHA(40) group. In contrast, perilla oil reduced PAF production by 50% as compared with safflower oil. Arachidonate (AA) in the PAF precursor, 1-alkyl-2-acyl-glycerophosphocholine, was roughly correlated with PAF production, but EPA and DHA in the precursor lipid were relatively unrelated. On the other hand, both PGE2 and LTB4 production correlated positively with AA and negatively with EPA and DHA in PMN phospholipids; EPA tended to be somewhat more effective than DHA in reducing PGE2 and LTB4 formation; the activity of perilla oil was no less than EPA(20). Thus, replacing safflower oil with perilla oil was no less effective than supplementing safflower oil with EPA or DHA (at 40% of total fatty acids) in reducing lipid mediator production in rat PMN.

Animals↗

Effect of dietary alpha-linolenate/linoleate balance on collagen-induced platelet aggregation and serotonin release in rats.

Male Sprague-Dawley rats at 3 weeks of age were weaned to a diet supplemented either with perilla seed oil [alpha-linolenic acid (alpha-LnA)/linoleic acid (LA) = 3.66] or with safflower seed oil (alpha-LnA/LA less than 0.01) for 5-6 weeks. The eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio in platelet phospholipids was much higher in the perilla oil group than in the safflower oil group. Platelet aggregability determined turbidometrically varied greatly among individual animals, and the difference in platelet aggregability between the two dietary groups was relatively small when higher concentrations (15 and 20 micrograms/ml) of collagen were used. However, when platelet aggregability was determined as an all-or-none phenomenon at lower concentrations (7.5 and 10 micrograms/ml) of collagen, a very distinct difference was observed between the two dietary groups; aggregability was much lower in the perilla oil group than in the safflower oil group. Collagen-induced serotonin release from platelets was significantly reduced in the perilla oil group as compared with the safflower oil group. These results emphasize the importance of estimating aggregability at threshold concentrations of collagen and confirm that dietary manipulation of the essential fatty acid balance could be useful in reducing the thrombotic tendency.

Animals↗