resolvin-d1 and Body-Weight

To investigate the influence of spleen deficiency on the epithelial barrier of jejunum and lungs in a rat model of spleen-deficiency and the effect and potential specialized pro-resolving mediators (SPMs) mechanism of chiropractic manipulation.. Three-week-old male Sprague-Dawley rats were divided randomly into normal control group (n = 6), spleen-deficiency group (n = 5) and chiropractic group (n = 6). Spleen-deficiency model was induced in spleen-deficiency group and chiropractic group. Moreover, chiropractic manipulation was performed in chiropractic group. Four weeks later, systemic Th1/Th2 balance was evaluated by the ratio of plasma interferon (IFN)-γ/interleukin (IL)-4 levels by enzyme-linked immunosorbent assay (ELISA). Epithelial barrier integrity were assessed by the observation of morphological changes by hematoxylin-eosin staining and zonula occludens (ZO)-1 gene expressions by quantitative real time polymerase chain reaction in jejunum and lungs. Plasma resolvin D1 (RvD1) and lipoxin A4 (LXA4) levels were measures by ELISA for endogenous SPMs production. The levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in jejunum and lungs were also measured by HPLC-MS/MS.. Comparing with normal control group, spleen-deficiency group showed disrupted mucosa in jejunum, inflammatory condition in lungs, significantly decreased ratio of plasma IFN-γ/IL-4 levels and lower expressions of ZO-1 mRNA in both jejunum and lung tissues. Comparing with spleen-deficiency group, chiropractic group had less disrupted mucosa in jejunum and inflammatory condition in lungs, significantly increased systemic ratio of IFN-γ/IL-4 and expressions of ZO-1 mRNA in both jejunum and lung tissues. Chiropractic group had significantly enhanced plasma levels of RvD1 and LXA4, but had no significantly higher levels of DHA and AA in jejunum and lungs when comparing with spleen-deficiency group.. Spleen deficiency caused systemic Th1/Th2 imbalance towards Th2 polarization and epithelial barrier disruption in jejunum and lungs. Chiropractic manipulation helped enhance endogenous SPMs production, which might be one of the action mechanism of chiropractic manipulation on the improvement of epithelial barrier disruption.

Topics: Animals; Arachidonic Acid; Body Weight; Docosahexaenoic Acids; Epithelium; Gene Expression Regulation; Interferon-gamma; Interleukin-4; Jejunum; Lipoxins; Lung; Male; Manipulation, Chiropractic; Rats; Rats, Sprague-Dawley; RNA, Messenger; Spleen; Zonula Occludens-1 Protein

We previously observed that resolvin D1 (RvD1), a metabolite of the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid, reduces infarct size by a mechanism involving the PI3-K/Akt pathway. In parallel, the beneficial effect of a high omega-3 PUFA diet on infarct size can be attenuated by increased omega-6 PUFA consumption. The present study was designed to determine if augmented linoleic acid (LA), an omega-6 PUFA administered at the same time, attenuates the cardioprotective action of RvD1. Male Sprague-Dawley rats received 0.1μg RvD1 alone or with one of three LA doses (1, 5 or 10μg) directly into the left ventricle chamber 5min before ischemia. The animals underwent 40min of ischemia by occlusion of the left descending coronary artery followed by 30min or 24h of reperfusion. Infarct size and neutrophil accumulation were evaluated after 24h of reperfusion, while caspase-3, -8 and -9 and Akt activities were assessed at 30min of reperfusion. LA attenuated cardioprotection afforded by RvD1, resulting in significantly increased infarct size. Neutrophil accumulation and Akt activity were similar between groups. Caspase activities, especially caspase-9, which could be activated by ischemia, were stimulated in the presence of LA, suggesting that this omega-6 PUFA accentuates ischemia intensity. The present results indicate that LA significantly attenuates the beneficial effect of RvD1 on infarct size. Therefore, reduction of omega-6 intake should be considered to maintain the protection afforded by RvD1.

Topics: Animals; Body Weight; Cardiotonic Agents; Caspases; Docosahexaenoic Acids; Hemodynamics; Linoleic Acid; Myocardial Infarction; Rats; Rats, Sprague-Dawley

Abdominal aortic aneurysm is associated with infiltration of inflammatory cells into the aortic wall. The inflammatory response is also evident in animal models, such as apolipoprotein E-deficient (ApoE-/-) mice that have been infused with angiotensin II, prior to development of aortic aneurysm. Since omega-3 polyunsaturated fatty acids (n-3 PUFAs) and their metabolites have anti-inflammatory and pro-resolving activity, we hypothesised that dietary supplementation with n-3 PUFAs would protect against inflammatory processes in this mouse model. Twenty C57 and 20 ApoE-/- 3-4 week old male mice were supplemented with a low (0.14%, n = 10/group) or high (0.70%, n = 10/group) n-3 PUFA diet for 8 weeks before 2-day infusion with 0.9% saline or angiotensin II (1000 ng/kg/min). Four ApoE-/- mice on the low n-3 PUFA diet and none of the ApoE-/- mice on the high n-3 PUFA diet showed morphological evidence of abdominal aortic dissection. The plasma concentration of the n-3 PUFA metabolite, resolvin D1 was higher in angiotensin II-infused ApoE-/- mice fed the high, compared to the low n-3 PUFA diet. The number of neutrophils and macrophages infiltrating the abdominal aorta was elevated in ApoE-/- mice on the low n-3 PUFA diet, and this was significantly attenuated in mice that were fed the high n-3 PUFA diet. Most neutrophils and macrophages were associated with dissected aortas. Immunoreactivity of the catalytic subunit of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, Nox2, and superoxide were elevated in ApoE-/- mice that were fed the low n-3 PUFA diet, and this was also significantly attenuated in mice that were fed the high n-3 PUFA diet. Together, the findings indicate that supplementation of ApoE-/- mice with a diet high in n-3 PUFA content protected the mice against pro-inflammatory and oxidative stress responses following short-term infusion with angiotensin II.

Topics: Angiotensin II; Animals; Aorta; Apolipoproteins E; Body Weight; Cholesterol; Dietary Supplements; Docosahexaenoic Acids; Fatty Acids, Omega-3; Inflammation; Macrophages; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Animal; NADPH Oxidase 2; NADPH Oxidases; Neutrophils; Oxidative Stress; Superoxides; Triglycerides