thromboxane-b2 and 14-15-epoxy-5-8-11-eicosatrienoic-acid

This study aimed to explore the metabololipidome in mice upon cupping treatment.. A nude mouse model mimicking the cupping treatment in humans was established by administrating four cupping sets on the back skin for 15 minutes. UPLC-MS/ MS was performed to determine the PUFA metabolome in mice skin and blood before and after cupping treatment. The significantly changed lipids were administered in macrophages to assess the production of pro-inflammatory cytokines IL-6 and TNF-α by ELISA.. The anti-inflammatory lipids, e.g. PGE1, 5,6-EET, 14,15-EET, 10S,17S-DiHDoHE, 17R-RvD1, RvD5 and 14S-HDoHE were significantly increased while pro-inflammatory lipids, e.g. 12-HETE and TXB2 were deceased in the skin or plasma post cupping treatment. Cupping treatment reversed the LPS-stimulated IL-6 and TNF-α expression in mouse peritoneal exudates. Moreover, 5,6-EET, PGE1 decreased the level of TNF-α, while 5,6-EET, 5,6-DHET downregulated IL-6 production in macrophages. Importantly, 14,15-EET and 14S-HDoHE inhibited both IL-6 and TNF-α induced by lipopolysaccharide (LPS). 17-RvD1, RvD5 and PGE1 significantly reduced the LPS-initiated TNF-α, while TXB2 and 12-HETE further upregulated the LPS-enhanced IL-6 and TNF-α expression in macrophages.. Our results reveal the identities of anti-inflammatory versus pro-inflammatory metabolipidome and suggest the potential therapeutic mechanism of cupping treatment.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 8,11,14-Eicosatrienoic Acid; Animals; Bone Marrow Cells; Cells, Cultured; Fatty Acids, Unsaturated; Hematoma; Interleukin-6; Lipids; Lipopolysaccharides; Macrophages; Male; Metabolome; Mice; Mice, Inbred C57BL; Mice, Nude; RAW 264.7 Cells; Skin; Thromboxane B2; Tumor Necrosis Factor-alpha; Up-Regulation

Epoxygenase metabolites of arachidonic acid are produced by several tissues and have been shown to inhibit in vitro platelet aggregation. The purpose of the present investigation was to determine whether 14,15- or 8,9-epoxyeicosatrienoic acid, epoxygenase derivatives of arachidonic acid, affect the speed of platelet aggregation in in vivo mouse cerebral arterioles.. We performed a craniectomy in 116 anesthetized male mice and observed the pial arterioles by microscopy. We induced in situ platelet aggregation using a mercury light and intravascularly injected fluorescein dye.. Indomethacin (0.5 mg/kg i.p.), a known cyclooxygenase inhibitor, and 14,15-epoxyeicosatrienoic acid (0.3 mg/kg i.v.) increased the time necessary for the light plus dye to induce the first arterial platelet aggregate by 35% and 26%, respectively, whereas 8,9-epoxyeicosatrienoic acid (0.3 mg/kg i.v.) had no effect. Analysis of mouse serum by radioimmunoassay showed that the degree of inhibition of platelet aggregation by indomethacin and epoxyeicosatrienoic acids correlated with the degree of inhibition of thromboxane production.. We conclude that 14,15-epoxyeicosatrienoic acid is a potent inhibitor of in vivo platelet aggregation but cannot conclusively confirm that its effect on aggregation occurs via its reduction of platelet thromboxane A2. Because epoxyeicosatrienoic acids are produced by several tissues, including brain and vascular tissue, they may be important in vivo modulators of platelet aggregation and hemostasis.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arterioles; Blood Platelets; Cerebrovascular Circulation; Indomethacin; Mice; Platelet Aggregation; Platelet Aggregation Inhibitors; Thromboxane B2

Topics: 8,11,14-Eicosatrienoic Acid; Arachidonic Acid; Arachidonic Acids; Aza Compounds; Blood Platelets; Calcimycin; Collagen; Cytochrome P-450 Enzyme System; Eicosanoids; Humans; Phosphoproteins; Platelet Aggregation; Platelet Aggregation Inhibitors; Prostaglandin Endoperoxides, Synthetic; Sulfides; Thromboxane B2