Corn Oil Group Research Articles

Membrane fluidity and fatty acid metabolism in kidney cells from rats fed purified eicosapentaenoic acid or purified docosahexaenoic acid

Rats were given a supplement (1.5 ml/day) of purified eicosapentaenoic acid (EPA, 20:5,n-3), purified docosahexaenoic acid (DHA, 22:6,n-3)), or corn oil for 10 days. Membrane fluidity, measured as the steady-state fluorescence polarization of diphenylhexatriene (DPH), was approximately 20% lower in kidney cells from rats fed purified EPA than in cells from the DHA-fed or corn-oil fed animals. The level of 20:5(n-3) in kidney phospholipids was 18 times higher in rats fed EPA, and four times higher in those fed DHA as compared to the corn-oil group. The level of arachidonic acid (20:4,n-6) was concomitantly decreased, while linoleic acid (18:2,n-6) was increased in kidney-phospholipids in the n-3 fatty acid fed rats. The proportion of 22:6(n-3) in kidney phospholipids was not affected by EPA supplementation, while the DHA diet slightly increased the level of this fatty acid. The distribution of phospholipid subclasses was significantly altered in that phosphatidylcholine was increased and phosphatidylethanolamine was concomitantly decreased. It is suggested that the decrease in 20:4(n-6) is relatively more important in the regulation of fluidity than a concomitant increase in 20:5(n-3). It is also suggested that the compensatory modifications of the phospholipid subclass distribution as a response to decreased 20:4(n-6)/20:5(n-3) ratio was not sufficient to maintain fluidity when the ratio was as low as in the present study. The incorporation of labelled linolenic acid (18:3,n-3) in phospholipids was decreased in cells from the n-3 supplemented rats. Since endogenous 22:5(n-3) in phospholipids was only increased in the EPA group, 22:6(n-3) only in the DHA group, and 20:5(n-3) in both, it is suggested that the decreased incorporation of labelled 18:3(n-3) into phospholipids of the DHA-fed rats in particular is correlated to the increased level of 22:6(n-3) in the membrane phospholipids. The incorporation of fatty acids into phopholipids may thus show substrate specificity, in that 22:6(n-3) is less exchangable with labelled 18:3(n-3) than is 20:5(n-3). These results demonstrate that increasing levels of n-3 fatty acids in membranes affect the uptake and intracellular metabolism of fatty acids as well as membrane fluidity in the kidney.

Dietary cholesterol supplementation protects against endothelial cell dysfunction mediated by native and lipolyzed lipoproteins derived from rabbits fed high-corn oil diets

Epidemiologic studies indicate that dietary plant fats are negatively and dietary cholesterol positively correlated with the incidence of cardiovascular disease. However, recent research suggests that unsaturated fats may be atherogenic because of their contribution to cellular oxidative stress and that cholesterol may exhibit antioxidant properties. To test this hypothesis, rabbits were fed diets containing 2 g corn oil/100 g diet, supplemented either with 16 g/100 g diet of corn oil (CO) or CO plus added cholesterol (CO+C) for 10 weeks. The cholesterol concentration in the CO+C diet was less than 30 mg cholesterol/100 g diet, which was sufficient to cause a significant rise in plasma and LDL cholesterol, but that did not lead to any detectable fatty steak or lesion formation. Compared with the native CO group, lipid hydroperoxide levels were significantly lower in both native lipoproteins ( VLDL LDL ) and lipolyzed remnants of this lipoprotein mixture derived from rabbits fed CO+C. This may be attributable in part to the observed decrease in unsaturated fatty acids as a result of dietary cholesterol supplementation. Relative to native lipoproteins, endothelial cells exposed to lipolyzed lipoprotein remnants experienced a significant increase in oxidative stress, as evidenced by increased DCF fluorescence, NF-ϰB, an oxidative stress sensitive transcription factor, was markedly induced in cells treated with both native and lipolyzed lipoproteins derived from the CO group, compared to the CO+C group. Independent of lipolysis, oxidative stress was markedly decreased in cells exposed to lipoproteins derived from animals fed CO+C, Furthermore, dietary cholesterol supplementation protected endothelial cells against lipolytic remnant-mediated barrier dysfunction. These data continue to support the hypothesis that lipolytic lipoprotein remnants are atherogenic and that small amounts of supplemental cholesterol may provide antioxidant protection.

The Fatty Acid Composition of Maternal Diet Affects Lung Prostaglandin E2 Levels and Survival from Group B Streptococcal Sepsis in Neonatal Rat Pups , , ,

Dietary fatty acid effects upon the immune system may be mediated in part by effects upon the synthesis of proinflammatory mediators. The effects of maternal dietary fatty acid composition upon lung prostaglandin (PG) E2 levels and survival from group B streptococcal (GBS) infection were investigated in neonatal rat pups. Beginning on d 2 of gestation and throughout lactation, pregnant dams were fed a purified diet whose fat source (22% of energy) was either corn oil or menhaden fish oil. On postnatal d 3, pups were randomly cross-fostered to dams of the same diet group to minimize litter effects; litters were then culled to 10 pups per dam. On postnatal d 7, pups were either injected with 1 × 107.5 GBS organisms or were killed for determination of lung tissue levels of PGE2 and lung and erythrocyte fatty acid composition. Arachidonic acid and PGE2 levels were significantly higher in the lungs of pups in the corn oil group compared with the fish oil group. Forty-nine percent of pups in the corn oil group survived the GBS challenge compared with 79% of pups in the fish oil group (P = 0.0005). These data suggest that the fatty acid composition of pre- and/or postnatal diet affects the neonatal response to immune challenge, which may be due in part to effects upon the synthesis of pro-inflammatory mediators.

Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids

To compare the effects of highly purified ethyl ester concentrates of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on serum lipids, apolipoproteins, and serum phospholipid fatty acids in humans, we conducted a double-blind, placebo-controlled, parallel design intervention study. Healthy nonsmoking men (n = 234) aged 36-56 y were randomly assigned to dietary supplementation with 3.8 g EPA/d, 3.6 g DHA/d, or 4.0 g corn oil/d (placebo) for 7 wk. Serum triacylglycerols decreased 26% (P < 0.0001) in the DHA group and 21% (P = 0.0001) in the EPA group compared with the corn oil group. Although not significant, net decreases in serum triacylglycerols were consistently greater in the DHA group across all quartiles of baseline triacylglycerol concentrations. Serum high-density-lipoprotein cholesterol increased 0.06 mmol/L (P = 0.0002) in the DHA group. In the EPA group, serum total cholesterol decreased 0.15 mmol/L (P = 0.02) and apolipoprotein A-I decreased 0.04 g/L (P = 0.0003). In the DHA group, serum phospholipid DHA increased by 69% and EPA increased by 29%, indicating retroconversion of DHA to EPA. In the EPA group, serum phospholipid EPA increased by 297% whereas DHA decreased by 15%, suggesting that EPA is not elongated to DHA in humans. The serum phospholipid ratio of n-3 to n-6 fatty acids increased in both groups, whereas the relative changes in n-6 fatty acids suggested possible alterations in liver desaturation activity in the DHA group. We conclude that both DHA and EPA decrease serum triacylglycerols, but have differential effects on lipoprotein and fatty acid metabolism in humans.

Dietary fish oil and fish and borage oil suppress intrapulmonary proinflammatory eicosanoid biosynthesis and attenuate pulmonary neutrophil accumulation in endotoxic rats.

Proinflammatory eicosanoids and cytokines are important mediators of local inflammation in acute lung injury. We determined if enteral nutrition with anti-inflammatory fatty acids, eicosapentaenoic acid, and gamma-linolenic acid would reduce the intrapulmonary synthesis of proinflammatory eicosanoids and cytokines and pulmonary neutrophil accumulation in a rat model of acute lung injury. Prospective, randomized, controlled, double-blind study. Research laboratory at a university medical center. Male Long-Evans rats (250 g). Rats were randomly assigned to three dietary treatment groups and fed nutritionally complete diets (300 kcal/kg/day) containing 55.2% of the total calories from fat with either 97% corn oil, 20% fish oil, or 20% fish and 20% borage oil for 21 days. On day 22, bronchoalveolar lavage was performed 2 hrs after an intravenous injection of Salmonella enteritidis endotoxin (10 mg/kg) or saline. Bronchoalveolar lavage fluid was analyzed for leukotriene B4, leukotriene C4/D4, thromboxane B2, prostaglandin E2, 6 keto-prostaglandin F1alpha, tumor necrosis factor (TNF)-alpha, and macrophage inflammatory protein-2 (MIP-2). Lung myeloperoxidase activity (a marker for neutrophil accumulation) and phospholipid fatty acid composition were also determined. Lung phospholipid concentrations of arachidonic acid were lower and the concentrations of eicosapentaenoic acid and docosahexaenoic acid were higher with fish oil and fish and borage oil as compared with corn oil. Dihomo-gamma-linolenic acid, the desaturated and elongated intermediate of gamma-linolenic acid, increased with fish and borage oil as compared with fish oil and corn oil. The levels of leukotriene B4, leukotriene C4/D4, 6-keto-prostaglandin F1alpha, and thromboxane B2 with corn oil were significantly increased with endotoxin as compared with saline. In contrast to the corn oil group, endotoxin did not significantly increase bronchoalveolar lavage levels of leukotriene B4, leukotriene C4/D4, and thromboxane B2 above those of saline-treated rats with fish oil and fish and borage oil. Lung myeloperoxidase activity was significantly increased in endotoxin-treated rats compared with those rats given saline in all dietary treatment groups. However, lung myeloperoxidase activity was significantly lower with either fish oil or fish and borage oil as compared with corn oil after endotoxin. Although endotoxin increased the levels of TNF-alpha and MIP-2 with all dietary treatment groups as compared with saline-treated rats, there were no significant differences in the levels of either cytokine between the dietary treatment groups. These results indicate that dietary fish oil and fish and borage oil as compared with corn oil may ameliorate endotoxin-induced acute lung injury by suppressing the levels of proinflammatory eicosanoids (but not TNF-alpha or MIP-2) in bronchoalveolar lavage fluid and reducing pulmonary neutrophil accumulation.

Subchronic oral toxicity of di- n-octyl phthalate and di(2-ethylhexyl) phthalate in the rat

The subchronic oral toxicity of di(2-ethylhexyl) phthalate (DEHP) and di- n-octyl phthalate (DNOP) was studied. Groups of 10 male and 10 female Sprague-Dawley rats were administered DEHP in the diet at 0, 5, 50, 500 or 5000 ppm for 13 wk. In a separate study, groups of 10 male and 10 female Sprague-Dawley rats were given DNOP (5, 50, 500 and 5000 ppm) in the diet while control groups received basal diet containing 4% corn oil and positive control groups were fed a diet containing 5000 ppm DEHP. Growth rate and food consumption were not affected by treatment with either compound. Hepatomegaly was observed in the highest dose groups of both sexes administered DEHP but not in the DNOP-treated animals. At the highest dose, DNOP caused threefold (females) and 12-fold (males) increases in liver ethoxyresorufin- O-deethylase activity while DEHP did not. Mild changes in serum biochemistries were mostly confined to rats in the highest dose group of DEHP, and included increased serum albumin and albumin/globulin ratio in both sexes and decreased cholesterol in female rats. Mild vacuolations in the Sertoli cells were observed in male rats exposed to 500 ppm DEHP. At 5000 ppm DEHP, there was mild to moderate seminiferous tubule atrophy and Sertoli cell vacuolation in males, and rats of both sexes showed hepatic peroxisome proliferation. Both DEHP and DNOP at 5000 ppm caused mild histological changes in the thyroid consisting of reduced follicle size and colloid density, and the liver consisting of endothelial nuclear prominence, nuclear hyperchromicity and anisokaryosis. There was accentuation of zonation of the hepatic lobules and increased perivenous cytoplasmic vacuolation in DNOP-treated rats. Trace quantities (3–5 ppm) of DEHP and DNOP were detected in the liver, and 15–31 ppm were found in adipose tissue of the highest dose groups. The no observed-effect-level was judged to be 50 ppm in the diet or 3.7 mg/kg body weight/day for DEHP, and 500 ppm or 36.8 mg/kg body weight/day for DNOP.

Fish Oil Effects on Tissular Fatty Acids and Plasma Lipid Peroxidation in Zinc Deficient Rats

Zinc has been reported to play a key role in lipid metabolism as well as in defences against oxidative stress. The aim of this work was to investigate the fatty acid distribution (plasma, heart, kidney, liver) and peroxidation (plasma) in zinc-deficient rats fed with n-6 fatty acids (10% corn oil) or n3 fatty acid fish oil (10% Maxepa). Zinc deficiency led to a decreased tissular and plasma n-6/n-3 ratio both in triglycerides and phospholipids. This effect was more marked in the Maxepa group than in the corn oil group. In plasma, the TBARs/TG + PL ratio was significantly enhanced in zinc-deficient animals, especially in rats receiving Maxepa. With regard to these results, zinc deficiency could appear as an aggravating factor of oxidative risk when associated with a n-3 fatty acid-rich diet. This work draws attention to the harmful oxidative risk associated with patients' intake of fish oil concentrate, without taking into account their antioxidant dietary intakes and status.

Dietary Lipid Source Alters Murine Macrophage/Vascular Smooth Muscle Cell Interactions in Vitro

This study was conducted to compare the impact of dietary lipids on the ability of macrophages to modulate vascular smooth muscle cell (SMC) DNA synthesis in vitro. C57BL/6 female mice were fed six different diets (6 mice/diet) containing 10% fat from corn oil (CO), borage oil (BO), primrose oil (PO), fish-corn oil mix (FC, 9:1, w/w), fish-borage oil mix (FB, 1:3, w/w), or fish-primrose oil mix (FP, 1:3, w/w) for 2 wk. Peritoneal macrophages were isolated from these mice, stimulated with zymosan or vehicle, and subsequently co-cultured with naive mouse aortic SMC in the presence of 3H-thymidine to measure SMC DNA synthesis. In this co-culture system, macrophages were seeded on 25-mm culture inserts (upper chamber) and SMC were seeded on 35-mm culture dishes (lower chamber). The two cell types were separated by a semipermeable membrane with a 30-kD cut-off. When quiescent SMC were co-cultured with macrophages, only the PO and FP diet groups had significantly (P < 0.05) lower SMC DNA synthesis compared with the control CO group whose diet contained no γ-linolenic acid (GLA) or (n-3) polyunsaturated fatty acids (PUFA). In contrast, when cycling SMC were co-cultured with dietmodulated macrophages, all dietary groups except for those fed FC had significantly lower (P < 0.05) SMC DNA synthesis relative to the CO group. Although the level of GLA in PO and BO diets was different (11.5 and 22.3 g/100 g fatty acids, respectively), these treatments exerted comparable inhibitory effects on SMC DNA synthesis. The FP treatment consistently exhibited the lowest SMC DNA synthetic profile among the six dietary groups irrespective of SMC growth conditions. These data suggest that BO and PO alone or in combination with fish oil influence macrophage/smooth muscle cell interactions in a manner consistent with favorable modulation of the atherogenic process.

The Role of Luminal Nutrients in Intestinal Injury from Mesenteric Reperfusion and Platelet-Activating Factor in the Developing Rat

Necrotizing enterocolitis (NEC) develops primarily after the onset of enteral feeds in the premature infant. The purpose of this study was to evaluate the influence of intestinal luminal nutrients on histologic injury and the oxidant response in a rat model of NEC. On postnatal Days 10 and 35, Sprague–Dawley rats (totaln= 81) underwent abdominal laparotomy. A control group received sham-injury only. The ischemia groups received a single intraluminal injection of 0.25 ml (Day 10) or 1.0 ml (Day 35) of lactose (8.6 g/dl), casein (2.2 g/dl), corn oil (4.4 g/dl), or infant formula (Similac; 20 g/dl). After injection of the nutrient solutions, ischemia groups underwent mesenteric occlusion for 1 hr and intraluminal injection of platelet-activating factor (50 μg/kg). Necropsies were performed after 6 hr or at demise. Intestinal samples were taken for histology, total glutathione (GSH; an antioxidant), and conjugated dienes (a lipid peroxidation product). Histologic injury was scored from 0 (normal) to 5 (transmural necrosis). Microscopic injury scores in the oil group were significantly higher than the casein group (P< 0.05) and trended toward being higher in the formula group (P= 0.085) at age 10 days. Total GSH activity was significantly higher in the sham groups than all ischemia groups on Day 10 (P< 0.001) and than the corn oil group on Day 35 (P< 0.05). GSH activity did not differ among ischemia groups. Conjugated diene concentrations were significantly higher in the casein group than the lactose and sham groups at age 10 days (P< 0.05) only. We conclude that intraluminal lipids may augment intestinal ischemic injury in the newborn (age 10 days) but not the weanling rat. While oxygen-free radicals were present during injury, lipid peroxidation from oxygen radicals was not responsible for this increase in histologic injury.

The Peroxisome Proliferators WY-14,643 and Methylclofenapate Induce Hepatocyte Ploidy Alterations and Ploidy-Specific DNA Synthesis in F344 Rats

WY-14,643 (WY) and methylclofenapate (MCP) are peroxisome proliferators (PP) and hepatocarcinogens in rats. MCP causes hepatic polyploidization and preferentially induces replicative DNA synthesis in binucleate tetraploid hepatocytes (2 × 2N) in young Alpk:AP rats. To compare the effect of WY and MCP on hepatocyte ploidy and ploidy-specific DNA synthesis, male F344 rats were fed WY (0.1% in diet) or gavaged with MCP (25 mg/kg/day in corn oil) for 2, 5, or 10 days. Four rats per treatment group (including corn oil and diet control groups) were euthanized and the livers perfused at each time point. To identify cells undergoing DNA synthesis, all animals received BrdU by continuous infusion for 2 or 5 days prior to euthanasia. Hepatocyte ploidy and DNA synthesis were determined using one- or two-parameter flow cytometry. Averages ± SEM for adult male F344 rats as a percentage of total hepatocytes for each ploidy subclass are 2N = 3.4 ± 0.7%, 4N = 69.9 ± 1.9%, 2 × 2N = 14.4 ± 2.4%, 8N = 2.2 ± 0.4%, and 2 × 4N = 9.6 ± 0.9%. Significant alterations were not induced in the proportions of 2 × 2N or 4N ploidy subclasses by WY or MCP at any time point. However, WY caused increases in 8N hepatocytes at 2, 5, and 10 days (2 days, 5.2% vs 2.2% for controls; 5 days, 7.0% vs 3.1% for controls; 10 days, 6.4% vs 3.6% for controls) as did MCP at 5 and 10 days (5 days, 6.3% vs 2.5% for controls; 10 days, 5.3% vs 2.9% for controls). In addition, a majority of BrdU-containing hepatocytes were 4N following 5 and 10 days of WY and MCP [34.3% (WY) and 16.8% (MCP) vs 1.8% and 1.1% for controls, respectively, for 2 × 2N (5 days) as a percentage of total hepatocytes]. Hepatocytes with intermediary DNA content (between tetraploid and octaploid) from MCP- and WY-treated rats were predominantly mononuclear, the percentage of binucleate hepatocytes being similar to or less than the percentage of binucleate cells within the total tetraploid hepatocyte population. These data suggest that polyploidization is induced by PP and induction of S-phase by WY and MCP occurs primarily in 4N hepatocytes in mature F344 rats and not within 2 × 2N hepatocytes. Identification of a ploidy subpopulation at risk for tumor development in rodents is essential for clarifying the role of cell replication in risk assessment studies of PP.

DIETARY FATTY ACID (FA) EFFECTS UPON GROUP B STREPTOCOCCAL (GBS) INFECTION.† 1893

Dietary FA effects upon the immune response may be mediated in part by effects upon proinflammatory cytokines and eicosanoids. The impact of maternal diet FA composition upon mortality from GAS infection was studied in neonatal rat pups. Methods: Timed pregnant dams were fed, beginning on day 2 of gest. and throughout lactation, either chow (control) or a purified diet whose fat source (22% of cals) was either corn oil (high n6) or menhaden fish oil (high n3). On day 3 of life, pups were culled to 10 pups per dam and were randomly cross-fostered among dams fed the same diets to minimize litter effects. Milk was removed from culled pup stomachs for FA analysis. Exp 1: On day 7 of life, pups were injected i.p. with 0.1 ml of a suspension of GAS Type I as follows: one litter per diet with 106.5 organisms, and one litter per diet with 107.5 organisms. Data from both doses were combined for statistical analyses. Exp 2: On day 7 of life, pups (n=1 litter per diet group) were injected with 107 GAS organisms and sacrificed 48 hours later. Blood was collected for GAS culture and analysis of serum TNFα levels; spleen weights were determined. Results: FA composition of milk reflected maternal diet (Table). Exp 1: 100% of pups in the chow and corn oil groups died within 96 hours, while 33% survived in the fish oil group (p=0.002 fisher's exact (permutation) test). Exp 2: Spleen weights (as% body weight) were significantly higher in the fish vs corn and chow groups. Preliminary cytokine data suggest lower serum levels of TNFα and a trend towards fewer positive blood culture in pups of the fish group. Conclusion: The FA composition pre- and/or postnatal diet may affect immune response to bacterial sepsis. Funded in part by Ross Laboratories.

Fish oil enhances macrophage tumour necrosis factor-alpha mRNA expression at the transcriptional level H. R. Chang, D. Arsenijevic, 1. Vladoianu,L. Girardier, A. G. Dulloo

The impact of fish oil on tumour necrosis-alpha (TNF-α) productionby macrophages stimulated by lipopolysaccharide (LPS) was examined in mice. Animals were fed high fat diets (20% fat wt/wt) rich in fish oil, corn oil or coconut oil for 4 weeks; a group of mice fed a low fat diet (5%) was included. Peritoneal macrophages were incubated with or without LPS for 24 h and the level of TNF-α measured in the culture medium. TNF-α mRNA was measured every 30 min for 2 h after addition of LPS by dot blot hybridization. Post-transcriptional studies were performed using actinomycin D and/or cycloheximide in the fish oil and corn oil groups. Production of TNF-a by macrophages was increased by more than 10-fold in the fish oil group compared to other groups; no difference was seen between low fat, corn oil and coconut oil groups. Compared to the low fat diet, higher levels of TNF-α mRNA were detected in the fish oil group (2.3-fold), and to a lesser extent in the coconut oil and corn oil groups (1.5- 1.2 fold, respectively). TNF-α mRNA accumulation in the fish oil group was not due to increased stability of mRNA and protein synthesis was not involved in this phenomenon. The authors discussed the mechanisms by which fish oil could increase TNF-α production by LPS stimulated macrophages.

Blood pressure-lowering effect of fish oil is independent of thromboxane A 2 level in spontaneously hypertensive rats

Whether the alterations in the synthesis of thromboxane A 2 (TXA 2) is the direct mechanism underlying the blood pressure-lowering effect of fish oil was investigated in this study. Six groups of 11 male spontaneously hypertensive rats were fed semipurified diets containing corn or fish oils and graded levels (50, 5000 or 15 000 ppm) of dietary vitamin E for 8 weeks. Plasma TXA 2, assayed by RIA, was significantly greater in the corn oil group than in the fish oil group ( P < 0.05). Compared to 50 ppm dietary vitamin E, 5000 and 15 000 ppm dietary vitamin E, respectively, significantly decreased plasma TXA 2 ( P < 0.05). Systolic, mean or diastolic blood pressure, evaluated by the tail cuff method, were significantly higher in the corn oil group than in the fish oil group ( P < 0.05). However, vitamin E had no effect on blood pressure. No relationship between TXA 2 and blood pressure was found. Experimental results indicated that the alterations in the synthesis of TXA 2 were not the direct antihypertensive effect of fish oil.

Dietary Effects of Corn Oil, Oleic Acid, Perilla Oil, and Primrose Oil on Plasma and Hepatic Lipid Level and Atherosclerosis in Japanese Quail.

To compare the atherogenecity of different fats and oils, a total of forty, 40-day-old male Japanese quails were fed one of the following diets for three months: basal diet (control), a diet-containing 15% corn oil (CO) and 2% cholesterol (CH), a diet-containing 15% oleic acid (OL) and 2% CH, a diet-containing 15% perilla oil (PE) and 2% CH, a diet-containing 15% evening [corrected] primrose oil (PR) and 2% CH. A higher plasma cholesterol concentration was found in the birds in the CO and OL groups, whereas the PE and PR groups showed a much lower level of plasma cholesterol than the CO and OL groups. In proportion to the increased plasma cholesterol, both CO and OL groups showed narrowing of the lumen of the ascending aorta and its large branches due to marked lipid-rich intimal thickening. Ultrastructural changes in the ascending aorta and its large branches were correlated with the degree of intimal thickening. The major foam cell types were macrophages and fibroblastic cells. The PE and PR groups showed the fewest lipid-rich intimal thickening lesions in their ascending aorta and its large branches. These findings suggest that the alpha-linolenic acid contained in perilla oil is less atherogenic than oleic and linoleic acid, and gamma-linolenic acid contained in evening [corrected] primrose oil has a tendency to decrease the plasma lipid level.

Lack of inhibitory effect of benzyl isothiocyanate on 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP)-induced mammary carcinogenesis in rats.

Modifying effects of benzyl isothiocyanate (BITC), a glucosinolate compound, were investigated on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis in female SD rats. One hundred twenty five female rats were divided into 4 groups. Starting at 6 weeks of age, rats were fed high fat diet containing 23.5% corn oil (Groups 1 and 4) or the experimental diet (high fat diet with 400 ppm BITC) (Groups 2 and 3). At 7 weeks of age, Groups 1 and 2 were given PhIP (100 mg/kg body weight, 8 times for 16 days) by intragastric tube. One week after the final PhIP treatment, the experimental diet for Groups 2 and 3 switched to high fat diet. At the termination (31 weeks after the start of experiment), mammary adenocarcinomas were recognized in Group 1 (PhIP alone) and Group 2 (PhIP + BITC). The incidence of neoplasms was 74.2% in Group 1, and 62.5% in Group 2. The multiplicity of them was 1.71 +/- 1.70 in Group 1, and 1.91 +/- 2.94 in Group 2. Mean sizes of tumors were 9.9 +/- 7.1 mm in Group 1, and 10.8 +/- 6.8 mm in Group 2. But no significant differences for tumors were available between the two groups. These results imply that the glucosinolate compound does not have clear inhibitory effects on PhIP-induced mammary carcinogenesis in rats.

Renal effects of dietary supplementation with fish oil in cyclosporine-treated liver transplant recipients

Nephrotoxicity is the main untoward effect of cyclosporine (CsA) treatment. Experimental and clinical data suggest that dietary supplementation with fish oil may lessen cyclosporine nephrotoxicity, possibly by lowering renal thromboxane (Tx) production. We have studied the renal effects of a daily supplementation for 2 months of 12 g fish oil (18% C20:5 n-3 eicosapentaenoic acid [Epa]and 12% C22:6 n-3 docosahexanoic acid [Dha]) in a placebo-controlled (12 g corn oil), prospective, randomized, double-blind study of stable CsAtreated liver transplant recipients. Thirteen patients ingested corn oil capsules and 13 fish oil. Compliance with dietary regimen was confirmed by fatty acid chromatography that showed increased plasma concentrations of EPA (from 0.4 ± 0.02% to 4.6 ± 0.5%, P < .0001) and DHA (from 1.8 ± 0.2% to 3.9 ± 0.1%, P < .0001) in the fish oil group and increased plasma concentration of linoleic acid (C18:2 n-6) in the corn oil group (from 25 ± 2% to 28.4 ± 2%, P < .001). At the end of the 2 months of the study, in the fish oil group the effective renal plasma flow increased by 22% ( P = .012), the glomerular filtration rate increased by 33% ( P = .057), the renal blood flow increased by 17% ( P = .024), and the calculated total renal vascular resistances decreased by 20% ( P = .034). In contrast, none of these parameters changed in the corn oil group. The renal functional reserve determined during l-arginine infusion, plasma renin activity (PRA), and plasma aldosterone (PA) remained unchanged during the study in either group. The urine excretion of Tx B 2 decreased from 707 ± 192 to 276 ± 76 pg/hr ( P = .013) in fish oil group, whereas it increased from 428 ± 195 to 870 ± 310 pg/hr ( P = .016) in corn oil group. In conclusion, 2 months of diet supplementation with fish oil in stable CsA-treated liver transplant recipients was associated with significant improvement of renal hemodynamics and with significant reduction of the renal production of TxB 2.

Renal effects of dietary supplementation with fish oil in cyclosporine-treated liver transplant recipients

Nephrotoxicity is the main untoward effect of cyclosporine (CsA) treatment. Experimental and clinical data suggest that dietary supplementation with fish oil may lessen cyclosporine nephrotoxicity, possibly by lowering renal thromboxane (Tx) production. We have studied the renal effects of a daily supplementation for 2 months of 12 g fish oil (18% C20:5 n-3 eicosapentaenoic acid [EPA] and 12% C22:6 n-3 docosahexanoic acid [DHA]) in a placebo-controlled (12 g corn oil), prospective, randomized, double-blind study of stable CsA-treated liver transplant recipients. Thirteen patients ingested corn oil capsules and 13 fish oil. Compliance with dietary regimen was confirmed by fatty acid chromatography that showed increased plasma concentrations of EPA (from 0.4 +/- 0.02% to 4.6 +/- 0.5%, P < .0001) and DHA (from 1.8 +/- 0.2% to 3.9 +/- 0.1%, P < .0001) in the fish oil group and increased plasma concentration of linoleic acid (C18:2 n-6) in the corn oil group (from 25 +/- 2% to 28.4 +/- 2%, P < .001). At the end of the 2 months of the study, in the fish oil group the effective renal plasma flow increased by 22% (P = .012), the glomerular filtration rate increased by 33% (P = .057), the renal blood flow increased by 17% (P = .024), and the calculated total renal vascular resistances decreased by 20% (P = .034). In contrast, none of these parameters changed in the corn oil group. The renal functional reserve determined during L-arginine infusion, plasma renin activity (PRA), and plasma aldosterone (PA) remained unchanged during the study in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dietary n-3, n-6 and n-9 polyunsaturated fatty acids on benzo( a)pyrene-induced forestomach tumorigenesis in C57BL6J mice

The modulating effect of dietary polyunsaturated fatty acids (PUFAs) on benzo( a)pyrene-induced forestomach tumorigenesis was assayed in mice fed with corn oil (CO), olein (O), Zizyphus mistol seed oil (MO), cod liver oil (CLO), and mixed fat (Stock diet). The fatty acid composition of liver lipids correlated well with the fatty acid composition of each diet. Only mice fed the O diet showed biochemical and clinical evidences of essential fatty acid deficiency (EFAD). Only 3 animals developed well-differentiated invading squamous cell carcinomas in the O group. The papilloma incidence was reduced in MO and CLO with respect to the O group. Forestomach papillomatosis was increased in mice fed an n-9 enriched diet in comparison to stock and CO groups. In comparison with stock mice, the frequency of multiple epidermoidal hyperplasia (MEH) was significantly decreased in the CLO group. Animals fed n-3 enriched diets (MO and CLO) showed significant antipromoting effect. These findings indicate that dietary fat can modulate tumorigenesis initiated in mouse forestomach by benzo( a)pyrene. In addition, the lack of action of an n-6 fatty acid-enriched diet in our experimental model suggests that the effect of PUFAs on tumorigenesis has target-tissue specificity. Mistol seed oil might be of potential value as a natural vegetable antipromoter nutrient.

Dietary γ-Linolenic Acid Modulates Macrophage–Vascular Smooth Muscle Cell Interactions

Macrophages and smooth muscle cells (SMCs) are two of the major reactive cell types in atherosclerosis, a disease characterized by uncontrolled proliferation of SMCs. The present study was designed to determine how dietary oils containing gamma-linolenic acid (GLA) (primrose oil [PO]) and long-chain n-3 fatty acids (fish oil) influence the ability of macrophages to modulate SMC DNA synthesis in vitro. Mice were fed one of four diets containing 10% (wt/wt) corn oil (CO), PO, fish oil-CO mix (FC; 9:1, wt/wt), or fish oil-PO mix (FP; 1:3, wt/wt) for 2 weeks. Resident peritoneal macrophages were isolated from these mice and seeded on a semipermeable membrane with a 30-kDa cutoff. Macrophages were preincubated with or without 50 mumol/L indomethacin (a cyclooxygenase inhibitor) or 50 mumol/L L655,238 (a 5-lipoxygenase inhibitor) for 30 minutes and subsequently cocultured with naive murine aortic SMCs grown on culture dishes. DNA synthesis in SMCs and prostaglandin formation in coculture supernatants were measured at the end of a 39-hour incubation period. SMC DNA synthesis was inhibited by 28% and 60% in PO and FP diets containing 10.1% and 8.2% GLA, respectively, relative to the control CO diet containing no GLA or long-chain n-3 fatty acid. A fourfold increase in the levels of PGE1, a potent antiproliferative eicosanoid derived from GLA, was observed in the PO and FP groups relative to the control CO group.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary fat and vitamin E have differential effects on serum lipid levels

The experiment was designed to study the effects of dietary fat and vitamin E on serum lipid status, an important indicator of risk for atherosclerosis. The influences of dietary fat and d,1-α-tocopheryl acetate (vitamin E) on serum fatty acid profiles, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride concentrations were studied in 40 weanling male Sprague-Dawley rats. Rats were fed semipurified diets containing corn oil or lard and graded levels (0, 100, 5000 or 15000 ppm) of vitamin E for 8 weeks. Serum vitamin E level was significantly greater in the corn oil group with 100 ppm vitamin E than in the lard group with 100 ppm vitamin E (p<0.05). Lipid status was verified by serum fatty acid profiles. Serum C18:0 (stearic acid) and C18:1 n-9 (oleic acid) of rats were significantly greater in the lard groups than in the corn oil groups with an equal amount of vitamin E except with the 100 ppm vitamin E, serum C18:2 n-6 (linoleic acid) of rats was significantly greater in the corn oil groups than in the lard groups with an equal amount of vitamin E, and C20:4 n-6 (arachidonic acid) of rats was significantly greater in the corn oil group with 15000 ppm vitamin E than in the lard group with 15000 ppm vitamin E (p<0.05). Rats fed corn oil had significantly greater serum HDL-cholesterol than rats fed lard with 100 or 15000 ppm vitamin E (p<0.05). However, serum LDL-cholesterol level was significantly greater in the rats fed corn oil with 100 ppm vitamin E compared with that in the rats fed lard with 100 ppm vitamin E (p<0.05). Both dietary fat and vitamin E had effects on serum HDL-cholesterol, however, no interaction existed between dietary fat and vitamin E on serum HDL-cholesterol. With regard to serum LDL-cholesterol, only vitamin E had a significant effect. The results suggested that both dietary fat and vitamin E can influence atherosclerosis progression via their effects on serum lipid status, but no interaction between them on serum lipid status was found.