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Objective To investigate the effect of 20‐HETE on the isolated myocardial ischemia reperfusion injury and to ex‐plore its underlying mechanisms .Methods Experiments were performed in isolated rat hearts subjected to 35 min of ischemia fol‐lowed by 40 min of reperfusion in Langendorff preparations .HET0016 (1 μmol/L) and various concentrations (10 ,30 or 50 nmol/L) of 20‐HETE were infused 10 min before the onset of ischemia and throughout the reperfusion period .Cardiac hemodynamic changes and myocardial contractility were continuously recorded with the Powerlab /8P system .Myocardial infarct size was meas‐ured by TTC staining .The level of ROS and the protein carbonyl content were determined by DHE fuorescence and DNPH method , respectively .Results Perfusion with HET0016 significantly improved myocardial ischemia reperfusion injury reduction in cardiac contractility ,after inhibited the production of 20‐HETE significantly reduced the occurrence of myocardial infarction area (P<0 .05) ,but exogenous join 20‐HETE aggravated I/R‐induced myocardial injury (P<0 .05) .Myocardial ischemia reperfusion injury significantly increased production of ROS and oxidative stress ,both of which were significantly inhibited by HET 0016 and enhanced by 20‐HETE administration(P< 0 .05) .Conclusion 20‐HETE stimulates ROS production and enhance protein carbonylation , which aggravates myocardial ischemia reperfusion injury .
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Objective To determine the relationship of cytochrome P-450 epoxygenase metabolites of arachidonic acids with impaired endothelium-dependent vasorelaxation in the healthy elderly. Methods A case-control study was employed.The study enrolled 60 healthy young adults (group A) and 60 healthy senior citizens (group B) of Han population in Shanghai. Serum contents of 14,15-dihydroxyeicosatrienoic acid (14,15-DHET) (a stable metabolite of 14,15-EET), 6-Kote-PGF1a (a stable metabolite of prostaglandin) and TXB2 (a stable metabolite of thromboxane A2) were measured using ELISA kits. The endothelium-dependent vasorelaxation (EDV) and endothelium-independent vasorelaxation (NEDV) in brachial arteries were determined by color Doppler ultrasound. Results Compared with group A, group B had significant higher levels of hemoglobin A1c, triglyceride and cholesterol levels (P＜0.01), and significant lower levels of 14,15-DHET and 6-Kote-PGF1a (P＜0.001), leading to increased values of TXB2/6-Kote-PGF1a and TXB2/14,15-DHET. There was bigger basal interior diameter of brachial arterials with reduced EDV and NEDV response (P＜0.01 and P＜0.05, vs. group A respectively) in group B. Moreover, the age was negatively correlated with 14,15-DHET and TXB2/14,15-DHET. Conclusions Our results indicate that the impaired EDV and NEDV in aging are associated with reduced production of arachidonic acid metabolites through cytochrome P-450 epoxygenase pathway and cyooxygenase pathway of endothelium in the healthy elderly.
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Objective To evaluate the alterations of thromboxane (TXB_2)、 prostacyclin (PGI_2)in murine acute pancreatitis (AP) and the therapeutic effect of calcium channel bocker-verapamil. MethodsA rat AP model was established to observe the alterations of plasma levels of TXB_2, 6-keto-PGF_ 1? and TXB_2/6-keto-PGF_ 1? ratio and the effect of verapamil. Pancreatic histology was examined by light and electron microscopy. ResultsAt 16 and 24 hours after induction of AP, the plasma levels of TXB_2[(1112?235)pg/ml、(1265?162)pg/ml] and TXB_2/6-keto-PGF_ 1? ratio(9.9?0.9,10.2?1.3)increased significantly. With varapamil therapy, the plasma levels of TXB_2[(671?102)pg/ml、(697?93)pg/ml] and TXB_2/6-keto-PGF_ 1? ratio (6.9?2.2)、(6.4?0.7) were dramatically lower than those in control group (P
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BACKGROUND AND OBJECTIVES: Both the granulation tissue and cholesterol granuloma can erode the surrounding bone and ossicles. However, the etiology of bone resorption in the granulation tissue and cholesterol granuloma has not been evident. The aim of this study was to assay the concentrations of arachidonic acid metabolites (AAMs) in cholesterol granuloma and the mastoid granulation tissue in order to better understand the possible role of AAMs in the pathophysiology of cholesterol granuloma in comparison with the granulation tissue. MATERIALS AND METHOD: Cholesterol granuloma tissues were obtained from eight patients who had underwent tympanomastoidectomy. Granulation tissues, which served for comparison, were taken from 12 patients who had underwent tympanomastoidectomy. Tissue concentrations of prostagladin (PG)E2, 6-keto-PGF1alpha, leukotriene (LT)C4, LTD4, LTE4, 15-hydro xyeicosatetraenoic acid (HETE), 12-HETE, 5-HETE, and thromboxane (TXB)2 were calculated using high performance liquid chromatography and compared between cholesterol granuloma and granulation tissue. RESULT: The level of 12-HETE was higher in cholesterol granuloma than in the granulation tissue. Among the PGs, the tissue concentration of PGE2 was particularly high in cholesterol granuloma than in the granulation tissue. LTD4 was the only LT detectable in cholesterol granuloma. In comparison to the AAMs in cholesterol granuloma, the lipoxygenase pathway products such as 12-HETE, 15-HETE, and 5-HETE were present in lower concentrations in the granulation tissue. LT was undetectable in the granulation tissues. CONCLUSION: Our results suggest that cholesterol granuloma and the granulation tissue is different not only in terms of histology, but also in terms of biochemical properties such as arachidonic acid metabolism.
Subject(s)
Humans , 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid , Arachidonic Acid , Arachidonic Acids , Bone Resorption , Cholesterol , Chromatography, Liquid , Cytochrome P-450 CYP1A1 , Dinoprostone , Granulation Tissue , Granuloma , Leukotriene D4 , Leukotriene E4 , Lipoxygenase , Mastoid , Metabolism , Otitis Media , OtitisABSTRACT
AIM: To observe whether arachidonic acid (AA) could induce apoptosis in mouse fibroblast cell line L929 and the potential mechanism involved. METHODS: The viability and damaged degree of L929 was monitored by MTT and the release of lactate dehydrogenase (LDH). Lipid peroxidation in L929 was measured as malondialdehyde (MDA) content by colorimetric assay. Hoechst 33258 staining was used to observe AA-induced morphological changes. Agarose gel electrophoresis was used to detect DNA fragmentation. RESULTS: Treatment of L929 cell with AA for 24 h, in the range of 40-160 ?mol/L, caused a great decrease in cell survival and increased MDA contents and the release of LDH simultaneously( P
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Epoxyeicosatrienoic acids(EETs)are the metabolic products of arachidonic acid(AA). They have the function of stimulating cell division, inhibiting platelet aggregation and regulating the transfer of cell calcium. In recent years, more and more people paid their attention to the effects of EETs on heart. This article will give a review about EETs and the relationship between EETs and heart.
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The hypoxic pulmonary vasoconstriction (HPV) in Yunan monkey has been observed. The results showed that acute alveolar hypoxia caused significant pulmonary hypertension, associated w~th art increase in pulmonary vascular resistance. The maximal response appeared 3 min after onset of hypoxia. Monkey may be proposed as moderate responder in HPV. The HPV in monkey was blocked by lipoxygenase inhibitor diethylcarbamazine and enhanced by cyclooxy genase blocker...indomethacin. It is suggested that lipoxygenase metabolites leukotrienes probably play the role of a mediator in HPV of monkey, whereas cyclooxygenase metabolites prostaglan dins act as medulator.
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The effects of PGE 1 and AA on hypoxic puImonary pressor response were studied in anesthetized young pig during hypobaric hypoxia simulating 4000 M altitude. After PGE1 injection, Ppa, PVR, Psa and SVR lowered immediately. AA injection enhanced HPPR but diminished Psa and SVR. The results obtained indicated that after AA injection, vasoconstriction PG (VCPG)was produced in pulmonary blood vessels, while vasodilation PG (VDPG)was produced in systemic blood vessels. It seemed that the effect of VCPG was more obvious than that of VDPG on pulmonary vasculature, thus, HPPR was enhanced by the former.