Dietary Dietary Docosahexaenoic Acid Research Articles

Enhanced radiosensitivity of rat autochthonous mammary tumors by dietary docosahexaenoic acid.

Dietary docosahexaenoic acid (DHA), which integrates into tumor cell membranes, has been reported to enhance the efficacy against tumors of cytotoxic drugs that induce reactive oxygen species (ROS). Because ionizing radiation also generate ROS, we initiated a study to determine whether dietary DHA might sensitize mammary tumors to irradiation. Mammary tumors were induced by N-methylnitrosourea (NMU) in Sprague-Dawley rats. The optimal dose of radiation to examine the effect of DHA on tumor response to irradiation was determined to be 18 grays (Gy) using a 4-6 MeV electron beam (according to the depth of the target volume) delivered in a single fraction from a linear accelerator. Two groups of rats were fed a basal diet containing 7% of a mixture of peanut and rapeseed oils enriched with 8% of an oil containing either a low (palm oil) or high (DHASCO oil containing 40% DHA) DHA content. DHA group was equally subdivided into 2 groups without or with addition of vitamin E (100 IU/kg diet). Irradiation was carried out when the first tumor in each rat reached 1.5 cm2 and subsequent change in tumor size was documented over time. DHA level in adipose tissue, taken as a biomarker, was higher in the DHA supplemented group compared to the control group. Vitamin E level in liver, the best storage for this compound, was higher in the vitamin E supplemented DHA group compared to the DHA group. Tumor size decreased by 60% at 12 days after irradiation in the DHA group vs. 31% in the control group (p = 0.03) and 36% in the DHA plus vitamin E group. Therefore, dietary DHA sensitized mammary tumors to radiation. The addition of vitamin E inhibited the beneficial effect of DHA, suggesting that this effect might be mediated by oxidative damage to the peroxidizable lipids.

Necessity of dietary lecithin and eicosapentaenoic acid for growth, survival, stress resistance and lipoprotein formation in gilthead sea bream Sparus aurata

The substitution of dietary docosahexaenoic acid (DHA) with eicosapentaenoic acid (EPA) reduces larval growth in gilthead sea bream. However, the value of EPA when dietary DHA is able to meet the requirements of the larvae has not been sufficiently studied. Dietary phosphoacylgliceride levels also affect fish growth and it has been suggested that they enhance lipid transport in developing larvae. The present experiment was carried out to further study the effect of dietary lecithin and eicosapentaenoic acid on growth, survival, stress resistance,. larval fatty acid composition and lipid transport, when DHA is present in the microdiets of gilthead:sea bream. Eighteen thousand gilt-head sea bream larvae of 4.99+/-0.53 mm total length were fed three microdiets tested by triplicate: a control diet [2% soybean lecithin (SBL) and 2.89% EPA], a low EPA diet,(2% SBL and 1.63% EPA) and a no SBL diet (0% SBL and 2.71% EPA). Handling, temperature and salinity tests determined larval resistance to stress. The results show that when dietary DHA levels are high, but dietary arachidonic acid (ARA) levels are about 0.2%, EPA is necessary to improve larval growth, and survival. Larval EPA content, but not DHA or ARA, was affected by dietary EPA levels. Increased dietary EPA improved larval stress resistance to handling and temperature tests, which could be related to its possible role as a regulator of cortisol production whereas it did not affect stress resistance after salinity shock. Larvae fed the no SBL diet showed a lower lipid content characterized by a low proportion of saturated and monounsaturated fatty acids, together with a significant reduction in the appearance of lipoprotein particles in the lamina propria and in the size of such particles, denoting a critical reduction in dietary lipid transport and utilization, and lower larval growth and survival rates.

Pharmacokinetics of Dietary 13C‐Labeled Docosahexaenoic Acid and Docosapentaenoic Acid in Red Sea Bream Chrysophrys major

AbstractThe objectives of this study were to investigate: 1) the pharmacokinetics of dietary docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) using 13C‐labeled fatty acids; 2) the interorgan transport of DHA in the red sea bream by monitoring the DHA level of several organs; and 3) the relationship between the plasma DHA level and optimum dietary DHA level in the plasma of the red sea bream Chrysophrys major. For this purpose, a mixture of 38.5% of [13C]DHA, 8.5% of [13C]DPA, and 4.2% of [13C]palmitic acid were given to the red sea bream at dose level of 8.0, 16.0, and 47.9 mg/kg by a single oral administration. For [13C]DHA, the maximum plasma concentration (tmax) occurred at 2.00–3.00 h after the oral administration. The peak plasma concentration (Cmax) and the area under the plasma concentration‐time curve to 24 h (AUC0‐24 for [13C]DHA level linearly increased with respect to dosage. [13C]DHA appeared in each organ (plasma, erythrocyte and the fat body of the orbit, liver, intestine, skin, brain, heart and muscle) at 0.5 h and was observed until 24 h. From the values determined for the pharmacokinetic parameters, the range of the effective plasma DHA level for normal growth of the red sea bream was suggested to be between 21.0 and 40.3 μg/mL. For [13C]DPA, the AUC0‐24 and Cmax values also linearly increased with the dosage, but tmax did not depend on it.

Dietary docosahexaenoic acid can alter the surface expression of CD4 and CD8 on T cells in peripheral blood.

The effect of dietary docosahexaenoic acid (DHA) on T cell states in peripheral blood was investigated. Weanling male C57Bl/6N mice were kept on one of three 10% fat diets containing various amounts of DHA and linoleic acid for 4 weeks. Changing the concentration of dietary DHA did not alter the proportion of T cells expressing CD4 or CD8. However, increasing the concentration of dietary DHA lowered the expression of CD4 and CD8 on the cell surface. The decreased expression of these surface molecules involved in T cell proliferation has serious implications in the role of DHA as an immunosuppressant.

Dietary docosahexaenoic acid suppresses inflammation and immunoresponses in contact hypersensitivity reaction in mice.

This study was designed to examine the immunomodulatory effects of dietary docosahexaenoic acid (DHA) in the absence of eicosapentaenoic acid (EPA). We investigated the effects of feeding dietary DHA ethyl ester (DHA-Et) (97% pure) at levels of 4.8 wt% of the total diet and of feeding EPA ethyl ester (EPA-Et) (99% pure) at 4.8 wt% on the inflammatory response in the challenge phase of the contact hypersensitivity reaction (CHR) in the ears of mice sensitized with 2,4-dinitro-1-fluorobenzene (DNFB). The effect of DHA-Et on T lymphocytes at the CHR site was examined using anti-CD4 antibodies. Furthermore, we examined the cytokines formed at the CHR site on the mRNA level. It was found that 24 h after the challenge, DHA-Et but not EPA-Et reduced the ear swelling. Infiltration of inflammatory cells, in particular, CD4-positive T lymphocytes, into the ears in the challenge phase of CHR was observed. DHA-Et reduced the infiltration of CD4-positive T lymphocytes into the ears. DHA-Et also decreased the expression of interferon-gamma, interleukin (IL)-6, IL-1beta, and IL-2 mRNA in ears. These observations suggest that DHA, but not EPA, may exert an antiinflammatory and immunosuppressive effect. The immunosuppressive effectiveness of fish oil may be attributed mainly to DHA.

The effects of a diet rich in docosahexaenoic acid on organ and vascular fatty acid composition in spontaneously hypertensive rats

Previous research has shown that dietary docosahexaenoic acid (DHA) attenuates the development of high blood pressure in young spontaneously hypertensive rats (SHR). The purpose of this study was to investigate the effects of dietary DHA on organ and vascular fatty acid composition in SHR. Given the important structural and functional role of fatty acids in cell membranes, alterations in fatty acid composition may contribute to the antihypertensive effect of DHA. SHR were fed a purified diet containing either a corn/soybean oil mixture (CSO, control) or a DHA-enriched oil for 6 weeks. The DHA diet markedly increased the levels of DHA in the aorta, renal artery, plasma, liver, heart, kidney, and lung by 5-, 15-, 7-, 6-, 3.8-, 3.5-, and 8.8-fold (P⪡0.001), respectively. The levels of eicosapentaenoic acid were also increased while there was a concomitant reduction in arachidonic and adrenic acids. Therefore, dietary DHA increases the incorporation of ω-3 polyunsaturated fatty acids in specific organs and vascular tissue in SHR at the expense of ω-6 polyunsaturated fatty acids.

Lymphatic Absorption of Chemically Structured Triglycerides Containing Docosahexaenoic Acid.

The effects of triglyceride (TG) structure on the lymphatic absorption of dietary docosahexaenoic acid (DHA) were studied in lymph-cannulated rats using chemically structured TGs containing DHA. When 1,3-dipalmitoyl-2-docosahexaenoylglycerol (PDP) and 1,2(or 2,3)-dipalmitoyl-3(or 1)-docosahexaenoylglycerol (PPD) were administered to rats, DHA located at the 2-position in PDP was absorbed more efficiently in lymph than that at the 1(or 3)-position in PPD. Total fatty acid composition of lymph TG in rats given PDP and PPD was nearly similar, but the contents of DHA located at the 2-position of lymph TG were much higher in the PDP group than in the PPD group. HPLC analysis showed that the lymphatic TG composition in the PDP group was different from that in the PDD group. These results showed that the TG structure could influence the lymphatic absorption of dietary DHA.

Is a dietary n-3 fatty acid supplement able to influence the cardiac effect of the psychological stress?

Epidemiological studies suggest that n-3 polyunsaturated fatty acids (PUFA) are involved in the prevention of cardiovascular disease. Stress is known to increase the incidence of CVD and the present study was realised to evaluate some physiological and biochemical effects of dietary docosahexaenoic acid (DHA) in male Wistar rats subjected to a psycho social stress. Rats were fed for 8 weeks a semi-purified diet containing 10% of either sunflower seed oil or the same oil supplemented with DHA. This food supply represented 50% of their daily requirement. The remaining 50% were supplied as 45 mg food pellets designed to induce stress in rats by an intermittent-feeding schedule process. The control group (n = 12) was fed the equivalent food ration as a single daily feeding. The physiological cardiovascular parameters were recorded by telemetry through a transmitter introduced in the abdomen. At the end of the experimentation, the heart and adrenals were withdrawn and the fatty acid composition and the catecholamine store were determined. Dietary DHA induced a pronounced alteration of the fatty acid profile of cardiac phospholipids (PL). The level of all the n-6 PUFAs was reduced while 22:6 n-3 was increased. The stress induced a significant increase in heart rate which was not observed in DHA-fed group. The time evolution of the systolic blood pressure was not affected by the stress and was roughly similar in the stressed rats of either dietary group. Conversely, the systolic blood pressure decreased in the unstressed rats fed DHA. Similar data were obtained for the diastolic blood pressure. The beneficial effect of DHA was also observed on cardiac contractility, since the dP/dt(max) increase was prevented in the DHA-fed rats. The stress-induced modifications were associated with an increase in cardiac noradrenaline level which was not observed in DHA-fed rats. The fatty acid composition of adrenals was significantly related to the fatty acid intake particularly the neutral lipid fraction (NL) which incorporated a large amount of DHA. Conversely, n-3 PUFAs were poorly incorporated in adrenal phospholipids. Moreover the NL/PL ratio was significantly increased in the DHA fed rats. The amount of adrenal catecholamines did not differ significantly between the groups. These results show that a supplementation of the diet with DHA induced cardiovascular alterations which could be detected in conscious animals within a few weeks. These alterations were elicited by a reduced heart rate and systolic and diastolic blood pressure.

Dietary Docosahexaenoic Acid Increases Cerebral Acetylcholine Levels and Improves Passive Avoidance Performance in Stroke-Prone Spontaneously Hypertensive Rats

We have recently shown that inferior performance in passive avoidance task is accompanied with decreased hippocampal choline (Ch) in stroke-prone spontaneously hypertensive rats (SHRSP) compared with normotensive control Wistar–Kyoto rats (WKY). We also reported that dietary docosahexaenoic acid (DHA) suppresses the development of hypertension and stroke-related behavioral changes, resulting in the prolongation of the life span of SHRSP. In this study, we examined the effect of dietary DHA on the cerebral acetylcholine (ACh) levels and learning performance in passive avoidance tasks in SHRSP. The arachidonic acid decreased and the DHA increased in plasma lipids dose dependently with dietary DHA treatments, which decreased the systolic blood pressure in SHRSP. Dietary DHA significantly restored the significantly inferior learning performance in passive avoidance response observed in control SHRSP (DHA 0%). Furthermore, the hippocampal ACh levels were correlated positively with the total response latency in passive avoidance tasks. These results suggest that cholinergic dysfunction in the brain of control SHRSP is responsible, at least in part, for the impaired learning ability and the dietary DHA ameliorates this performance failure.

Effects of dietary docosahexaenoic acid on survival time and stroke-related behavior in stroke-prone spontaneously hypertensive rats

1. 1. Dietary docosahexaenoic acid (DHA) suppressed the age-dependent increase in systolic blood pressure and prolonged the average survival time of stroke-prone spontaneously hypertensive rats (SHRSP). 2. 2. Dietary DHA (1% and 5% in diets) altered the circadian rhythm of SHRSP, causing significant increases in ambulatory activity during the dark period. At the onset of stroke, desynchronization with light and dark phases and new biological rhythms were noted in all of the control SHRSP (DHA 0%). DHA-treated SHRSP did not show such behavioral changes. 3. 3. These effects were accompanied by the increase of DHA and the decrease of AA levels in plasma and brain cortex. 4. 4. It was concluded that dietary DHA suppresses the development of hypertension and stroke-related behavioral changes, resulting in prolongation of the SHRSP's life span.

Effect of dietary docosahexaenoic acid in the rat middle cerebral artery thrombosis model

We investigated the effect of dietary docosahexaenoic acid (DHA) supplementation on the thrombolytic efficacy of recombinant tissue-type plasminogen activator (rt-PA), platelet aggregability, serum cholesterol and phospholipids. Male Wistar rats (6 weeks old) received dietary DHA supplementation (300 mg/kg per day) for 8 weeks. The rat middle cerebral artery (MCA) was occluded by a thrombus induced by photochemical reaction between rose bengal and green light which cause endothelial damage followed by platelet adhesion, aggregation and formation of a platelet and fibrin-rich thrombus at the site of photochemical reaction. The MCA blood flow was monitored using a laser Doppler flowmeter. rt-PA was administered 30 min after the middle cerebral artery had been occluded by a thrombus. This regimen produced a significant (P<0.05) decrease in serum free-cholesterol and phospholipids levels, inhibited platelet aggregation ex-vivo induced by collagen in whole blood (P<0.05), reduced thromboxane (TX) B 2 formation (P<0.01) in whole blood and prolonged the time for thrombotic MCA occlusion (P<0.01) as compared with values obtained from animals on standard diet. Further, dietary DHA enhanced thrombolytic efficacy of rt-PA and reduced the size of ischaemic cerebral lesions. Our findings suggest that dietary DHA produces antithrombotic effects via metabolic conversion to non-atherogenic and non-platelet stimulant metabolites.

Effect of Dietary Docosahexaenoic Acid Supplementation on Platelet Function: Studies in the Rat Femoral Artery Thrombosis Model

We have developed a model whereby the femoral artery in an experimental animal can be occluded by a photochemical reaction between rose bengal and green light which causes endothelial injury followed by platelet adhesion, aggregation and formation of a platelet rich thrombus at the site of the reaction. Using this model, we investigated the effect of dietary docosahexaenoic acid (DHA) supplementation on platelet aggregation and on serum cholesterol and lipids. Male Wistar rats (iweeks-old) received dietary DHA supplementation (300 mg/kg/d) for 8 weeks. This regimen produced a significant (p < 0.05) decrease in serum free-cholesterol and phospholipids levels, inhibited platelet aggregation ex vivo induced by collagen in whole blood (p < 0.05) but not in platelet rich plasma, reduced thromboxane B(2) formation (p<0.01) induced by collagen in washed platelets and prolonged the time for thrombotic arterial occlusion (p<0.01) as compared with values obtained in animals on standard diet. In conclusion, dietary DHA produces antithrombotic effects such as reduction in platelet aggregability and lowering of plasma cholesterol. Whole blood where red and white blood cells can exert their influences on platelet function is a more sensitive and physiological medium than platelet rich plasma for studying the effects of antithrombotic treatments on platelet aggregability ex vivo.