6-ketoprostaglandin-f1-alpha and Metabolic-Syndrome

Objective: To trace the development of disorders intravascular platelet activity in experimental form of the metabolic syndrome. The study included 61 rat male Wistar rats at the age of 2.5-3 months. Animals were divided into 2 groups: 32 rats were given free access to drink 10% solution of fructose for 8 weeks and 29 rats were the control group. The level of the total cholesterol, high density lipoprotein cholesterol (HDLD cholesterol) and triglycerides were determined using colorimetric enzymatic method. The blood plasma content of endothelin-1 was determined by radioimmunoassay, thromboxane B2 and 6-keto-prostaglandin F(1α)--by ELISA. The total content of nitrogen oxide metabolites was revealed in blood. Intravascular platelet activity was assessed using phase contrast microscopy. In terms of fructose load in rats simultaneously with the increase of body weight and the development of biochemical disorders that are characteristic for the metabolic syndrome, there comes a marked progressive increase in intravascular platelet activity [reduction of the number of discocytes from 81.0 ± 0.1 to 61.3 ± 0.2%, increase in the number of reactive platelets from 19.0 ± 0.1 to 38.7 ± 0.2%, an increase in the number of freely moving in the blood of small units from 2.4 ± 0.0 to 14.6 ± 0.1 per 100 free platelets, and of medium and large units (from 4 or more cells) from 0.1 ± 0.03 to 2.3 ± 0.06 per 100 free platelets], largely due to the increase (p < 0.01) of the synthesis of thromboxane B2 (from 145.9 ± 0.2 to 232.6 ± 0.7 pg/ml), endothelin-4 (from 6.9 ± 0.2 to 12.5 ± 0.4 pg/ml) and reduction (p < 0.01) of the generation of 6-keto-prostaglandin F1α (from 75.9 ± 0.2 to 62.3 ± 0.4 pg/ml), and the total amount of nitric oxide metabolites (from 27.9 ± 0.3 to 23.2 ± 0.1 mmol/l).

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Platelets; Endothelin-1; Fructose; Male; Metabolic Syndrome; Nitric Oxide; Platelet Activation; Rats; Rats, Wistar; Thromboxane B2

We have previously shown nutritional intervention with fish oil (n-3 PUFA) to reduce numerous complications associated with the metabolic syndrome (MetS) in the JCR:LA-corpulent (cp) rat. In the present study, we sought to explore the potential role of fish oil to prevent glomerulosclerosis in JCR:LA-cp rats via renal eicosanoid metabolism and lipidomic analysis. Male lean and MetS JCR:LA-cp rats were fed a lipid-balanced diet supplemented with fish oil (5 or 10 % of total fat). After 16 weeks of feeding, albuminuria was significantly reduced in MetS rats supplemented with 5 or 10 % fish oil ( - 53 and - 70 %, respectively, compared with the untreated MetS rats). The 5 % fish oil diet resulted in markedly lower glomerulosclerosis ( - 43 %) in MetS rats and to a lesser extent in those supplemented with 10 % fish oil. Interestingly, untreated MetS rats had higher levels of 11- and 12-hydroxyeicosatetraenoic acids (HETE) v. lean rats. Dietary fish oil reduced these levels, as well as other (5-, 9- and 15-) HETE. Whilst genotype did not alter prostanoid levels, fish oil reduced endogenous renal levels of 6-keto PGF1α (PGI2 metabolite), thromboxane B2 (TxB2), PGF2α and PGD2 by approximately 60 % in rats fed 10 % fish oil, and TxB2 ( - 50 %) and PGF2α ( - 41 %) in rats fed 5 % fish oil. In conclusion, dietary fish oil prevented glomerular damage in MetS rats and mitigated the elevation in renal HETE levels. These results suggest a potential role for dietary fish oil to improve dysfunctional renal eicosanoid metabolism associated with kidney damage during conditions of the MetS.

Topics: 6-Ketoprostaglandin F1 alpha; Albuminuria; Animals; Dietary Fats; Dietary Supplements; Dinoprost; Disease Models, Animal; Fish Oils; Genotype; Hydroxyeicosatetraenoic Acids; Kidney Diseases; Kidney Glomerulus; Male; Metabolic Syndrome; Prostaglandin D2; Prostaglandins; Rats; Rats, Inbred Strains; Thromboxane B2

The work was designed to study levels of serum prostaglandin F1a (6-keto-PGF1a), thromboxane B2, and leukotriene B4 (LTB4)--stable products of cyclooxygenase and lipogenase-catalyzed reactions of arachidonic acid, in patients with metabolic syndrome (MS) differing in glucose homeostasis. It was shown that MS is associated with excess production of anti-inflammatory oxilipines (LTB4) regardless of the presence or absence of insulin resistance. LTB4 are known to influence inflammatory processes due to compensatory synthesis of vasodilating eicosanoids (6-keto-PGF1a) that antagonize vasoconctriction and inflammation. Combination of MS with insulin resistance in patients with elevated LTB4 and 6-keto-PGF1a levels is associated with enhanced synthesis of thromboxane A2 responsible for vasoconstriction, platelet formation, and development of endothelial dysfunction. The study suggests disturbed synthesis of eicosanoids in patients with MS and their important role in pathogenesis of this condition.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Eicosanoids; Female; Humans; Insulin Resistance; Leukotriene B4; Male; Metabolic Syndrome; Middle Aged; Thromboxane B2; Young Adult

This study analyzes the effects of sodium tungstate and vanadyl sulphate in the fructose-overloaded rat, a model of metabolic syndrome. Fructose (9 weeks) increased blood pressure, triglycerydemia, glycemia, and reduced release of vasodilator prostaglandins (prostacyclin and prostaglandin E2 ) in the mesenteric vascular bed. Sodium tungstate prevented those alterations; meanwhile vanadyl sulfate only prevented the increase in glycemia. In conclusion, the present experiments showed that sodium tungstate is more effective than vanadyl sulfate for the treatment of experimental metabolic syndrome in rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta, Thoracic; Blood Glucose; Blood Pressure; Blood Pressure Determination; Chromatography, Reverse-Phase; Dinoprostone; Disease Models, Animal; Endothelium, Vascular; Fructose; Hypertension; Male; Mesenteric Arteries; Mesenteric Veins; Metabolic Syndrome; Rats; Rats, Sprague-Dawley; Risk Factors; Triglycerides; Tungsten Compounds; Vanadium Compounds

1.-- In the rat, a fructose-enriched diet induces hyperglycaemia, hypertriglyceridaemia, insulin resistance and hypertension; a model which resembles the human metabolic syndrome. 2.-- Prostanoids, metabolites of arachidonic acid, include vasoactive substances synthesized and released from the vascular wall that have been implicated in the increase of peripheral resistance, one of the mechanisms involved in the fructose-induced hypertension. 3.-- The aim of the present study was to: (i) analyse the effects of the in vitro incubation with fructose on the production and release of prostanoids in rat thoracic aorta and in rat mesenteric bed and (ii) compare the effects of incubation with those of the in vivo acute and chronic treatment of rats with fructose and with the combination of both in vivo and in vitro procedures. 4.-- Blood pressure, glycaemia and triglyceridaemia were significantly elevated in both 4- and 22-week fructose-treated groups. Meanwhile, body and heart weight as well as insulinaemia were similar between experimental animals and controls. 5.-- In aortae, 4 weeks of Fructose treatment did not modify the prostanoid pattern release, but in vitro incubation decreased prostacyclin (PGI(2)) production. However, after 22 weeks, fructose treatment and incubation exerted the same effect. 6.-- In mesenteric bed, after 4 weeks, the incubation and the combination of both procedures reduced the release of the vasodilators PGI(2) and PGE(2), while fructose treatment only diminished the PGE(2) release. On the contrary, the production of the vasoconstrictor thromboxane A(2) (TXA(2)) was enhanced by incubation and both the procedures. After 22 weeks, fructose treatment increased PGI(2) release, while it was reduced by incubation. The combination of both did not modify this peripheral resistance when compared with controls. Finally, incubation of tissues from treated rats increased the release of the vasoconstrictors, PGF(2alpha) and TXA(2). 7.-- In conclusion, the mesenteric bed, a resistance vascular bed, seems to be more sensitive than the aorta, a conductance vessel, to the effects of fructose on prostanoid production. This difference could be related to a more relevant role of resistance vessels in the regulation of peripheral resistance and consequently of blood pressure. The observed effects should contribute to a shift in the balance of the release of prostanoid in favour of vasoconstrictor metabolites. This phenomenon could be related to an increa

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Animals; Aorta, Thoracic; Blood Pressure; Dinoprostone; Disease Models, Animal; Fructose; Hypertension; In Vitro Techniques; Male; Mesenteric Arteries; Mesenteric Veins; Metabolic Syndrome; Prostaglandins; Rats; Rats, Sprague-Dawley; Thromboxane A2