4-7-10-13-16-19-docosahexaenoic-acid-ethyl-ester and Disease-Models--Animal

This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA-ethyl ester (EPA-Et; E group), or DHA-ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P ≤ 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P ≤ 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P ≤ 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P ≤ 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P ≤ 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dietary Supplements; Disease Models, Animal; Docosahexaenoic Acids; Eicosapentaenoic Acid; Electrocardiography; Heart Failure; Heart Ventricles; Leukocytes, Mononuclear; Male; Organ Size; Rats; Rats, Sprague-Dawley; Survival Analysis; Ventricular Dysfunction, Right

Since omega-3 polyunsaturated fatty acids (n-3 PUFAs) can alter ventricular myocyte calcium handling, these fatty acids could adversely affect cardiac contractile function, particularly following myocardial infarction. Therefore, 4 wk after myocardial infarction, dogs were randomly assigned to either placebo (corn oil, 1 g/day, n = 16) or n-3 PUFAs supplement [docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) ethyl esters; 1, 2, or 4 g/day; n = 7, 8, and 12, respectively] groups. In vivo, ventricular function was evaluated by echocardiography before and after 3 mo of treatment. At the end of the 3-mo period, hearts were removed and in vitro function was evaluated using right ventricular trabeculae and isolated left ventricular myocytes. The treatment elicited significant (P < 0.0001) dose-dependent increases (16.4-fold increase with 4 g/day) in left ventricular tissue and red blood cell n-3 PUFA levels (EPA + DHA, placebo, 0.42 +/- 0.04; 1 g/day, 3.02 +/- 0.23; 2 g/day, 3.63 +/- 0.17; and 4 g/day, 6.97 +/- 0.33%). Regardless of the dose, n-3 PUFA treatment did not alter ventricular function in the intact animal (e.g., 4 g/day, fractional shortening: pre, 42.9 +/- 1.6 vs. post, 40.1 +/- 1.7%; placebo: pre, 39.2 +/- 1.3 vs. post, 38.4 +/- 1.6%). The developed force per cross-sectional area, changes in length- and frequency-dependent behavior in contractile force, and the inotropic response to beta-adrenoceptor activation were also similar for trabeculae obtained from placebo- or n-3 PUFA-treated dogs. Finally, calcium currents and calcium transients were the same in myocytes from n-3 PUFA- and placebo-treated dogs. Thus dietary n-3 PUFAs did not adversely alter either in vitro or in vivo ventricular contractile function in dogs with healed infarctions.

Topics: Animals; Calcium; Dietary Supplements; Disease Models, Animal; Docosahexaenoic Acids; Dogs; Dose-Response Relationship, Drug; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Female; Heart Ventricles; Male; Myocardial Contraction; Myocardial Infarction; Myocardium; Patch-Clamp Techniques; Ultrasonography; Ventricular Function, Left

Previous studies have demonstrated that dietary fish oil preparations have anti-inflammatory effects in humans and in experimental animals, but the individual components of fish oils that are responsible for their anti-inflammatory effects have not been documented. We therefore investigated in (NZB x NZW)F1 mice, a model for human systemic lupus erythematosus, the effects of diets containing ethyl esters of two purified n-3 fatty acids, eicosapentaenoic acid (EPA-E) and docosahexaenoic acid (DHA-E), a refined fish oil triglyceride (FO) which contained 55% n-3 fatty acids, and beef tallow (BT) which contains no n-3 fatty acids. The diets were initiated prior to the development of overt renal disease at age 22 weeks, and continued for 14 weeks. The extent of the renal disease was quantified by light microscopy and by proteinuria. Diets containing either 10 wt% FO, 10% EPA-E, or 6% or 10% DHA-E alleviated the severity of the renal disease, compared to the BT diet, whereas diets containing either 3% or 6% EPA-E or 3% DHA-E were less effective. Two diets containing approximately 3:1 mixtures of EPA-E and DHA-E alleviated the renal disease to a greater extent than expected for either of these fatty acids given singly. We believe that these experiments provide the first demonstration of anti-inflammatory effects of individual dietary n-3 fatty acids. The results also indicate that the anti-inflammatory effects of fish oils depend on synergistic effects of at least two n-3 fatty acids.

Topics: Animals; Autoimmune Diseases; Cattle; Dietary Fats; Disease Models, Animal; Docosahexaenoic Acids; Drug Synergism; Eicosapentaenoic Acid; Fats; Fatty Acids, Omega-3; Female; Kidney Glomerulus; Lupus Erythematosus, Systemic; Lupus Nephritis; Mice; Mice, Inbred NZB; Proteinuria