Effects of prostaglandin E1 on high density lipoprotein-phospholipid composition

Serum high-density phospholipids (HDL-phospholipids) composition was determined in rats treated with prostaglandin E1 (PGE1) and control group treated with isotonic saline. Total phospholipids and HDL-phospholipids levels at serum were found lower in rats treated with PGE1, than in controls. Considering the individual phospholipid classes of HDL, we observed that phosphatidylocholine (PC), phosphatidylinositol (PI) and diphosphatidylglycerol (DPG) serum concentrations were significantly higher in treated rats than in controls (P<0.001, P<0.005 and P<0.05 respectively). Furthermore, the serum concentrations of lysophosphatidylocholine (LPC) and phosphatidylserine (PS) were significantly lower in treated rats than in controls (P<0.01 and P<0.001 respectively). These findings suggest that PGE1 influences the composition of HDL-phospholipids and possibly modifies their action on lipid metabolism.     

Interaction of prostaglandin E1 with human high density lipoproteins

The assembly of cytochrome c oxidase subunits I-III was studied in vitro in isolated rat liver mitochondria pre-labeled with [35S]methionine. Individual subunits were immunoabsorbed with monospecific antibodies. Isolated heme a from rat liver mitochondria, when added to radiolabeled mitochondria, induced assembly of subunit I with subunits II and III. Assembly of these subunits was not observed in mitochondria incubated in the presence of heme b(hemin) or in the absence of heme. Quantitative analysis of immunoabsorbed, radiolabeled subunits suggests that the predominant effect of heme a is on the assembly of subunit I with subunit III.     

Influence of a type 2 diabetes associated prostaglandin E synthase 2 polymorphism on blood prostaglandin E2 levels

In this study we tested whether the type 2 diabetes mellitus associated prostaglandin E synthase 2 arginine to histidine polymorphism at position 298 (R298H) influences prostaglandin E2 levels in humans. Fasting prostaglandin E2 was determined in the blood of subjects carrying different genotypes of the R298H polymorphism. Subjects were matched by sex, age, and body mass index. No differences in prostaglandin E2 levels were found with respect to genotypes when considering the whole group. Male homozygous histidine carriers showed elevated prostaglandin E2 levels compared to heterozygous carriers and homozygous arginine carriers (188.2±42.4 vs. 80.4±26.5 pg/ml, p=0.021; and vs. 92.9±15.3 pg/ml, p=0.11). These differences were not evident in female subjects. In contrast, 6-keto-prostaglandin F1alpha levels as independent marker of arachidonic acid metabolism showed ambiguous results. Nevertheless, preliminary evidence of the prostaglandin E synthase 2 R298H polymorphism possibly influencing prostaglandin E2 blood levels in a gender-specific manner was obtained.     

Influence of spironolactone on urinary prostaglandin E2 and kinin excretion in rats

Spironolactone was administered to spontaneously hypertensive rats (SHRs) in order to examine the urinary excretions of prostaglandin E2 (PGE2) and kinin. Thirteen SHRs were divided into 2 groups: 0.1 ml of sesame oil was administered to one group (the spironolactone-lactone-untreated group, n = 6) and 20 mg of spironolactone in 0.1 ml of sesame oil was administered to the other group (the spironolactone-treated group, n = 7) by the subcutaneous route for 10 days in succession. Determinations were then made of the body weight, blood pressure, urine volume, and excretion levels of Na, K, kinin and PGE2 in the 24-hour urine. After the animals had been killed by decapitation, blood samples were drawn for determination of the plasma renin activity (PRA). The results obtained indicated decreased blood pressure and increased urinary Na excretion in the spironolactone-treated group. On the other hand, the PGE2 excretion level in the 24-hour urine decreased markedly immediately after administration of spironolactone (p less than 0.05) and was maintained at lower levels up to the end of the experiment. However, the 24-hour urinary kinin levels showed similar changes in both the spironolactone-treated group and the untreated group with no significant difference between them. These findings suggest that spironolactone has a suppressive effect on urinary PGE2 excretion, the activity of which is not mediated by kinin production in the kidneys but is the result of a direct action of spironolactone itself.     

Influence of prostaglandins on the lipid transfer between human high density and low density lipoproteins

Prostaglandin (PG) E₁ was demonstrated to stimulate the transfer of phosphatidylcholine and cholesterol esters from human high density lipoproteins (HDL₃) to low density lipoproteins (LDL). The enhancement effect of PGE₁, on the interlipoprotein lipid transfer was seen at low PG concentrations under conditions of spontaneous exchange as well as in the presence of lipoprotein-depleted plasma, or partly purified plasma lipid exchange protein. PGE₂ and PGF₂ showed no significant influence on the interlipoprotein lipid transfer. Evidence is presented suggesting that the PGE₁-induced stimulation of interlipoprotein lipid exchange results in enhancement of LCAT-catalyzed cholesterol esterification in plasma. It is proposed that the effect of PGE₁ is due to the previously described PGE₁-induced reorganization of the HDL surface [(1984) FEBS Lett. 173, 291-293] and that PG-lipoprotein interaction may be a factor regulating cholesterol homeostasis.     

Pancreatic secretion in rats treated with intra-aortic prostaglandin E1

The effects from one dose of PGE1 on the endocrine pancreatic secretions have been studied in rat. The dose is injected i.a. very near the pancreas in the abdominal aorta at the level of the caeliac artery. Glycemia, insulinemia and glucagonemia are studied after i.v. glucose injection in: a) normal rats; b) rats free from their endogenous rate of PGs by previous treatment with indomethacin i.p. and c) with an excessive rate of PGE1. The treatment with PGE1 produces an inhibitory effect on the insulinic response to glucose, as well as hyperglycemia and hyperglucagonemia. In the cases without the endogenous rat of PGs the insulinic secretion as a response to glucose is greatly improved.     

Influence of human low density and high density lipoprotein cholesterol on the in vitro prostaglandin I2 synthetase activity

We investigated in vitro the influence of low density lipoprotein (LDL) cholesterol and high density lioprotein (HDL) cholesterol separated from human serum on prostaglandin I2 synthetase activity studied by the conversion of prostaglandin H2 to prostaglandin I2 by the microsomal fraction of pig aorta. 6-Oxo-prostaglandin F1 alpha was analyzed by gas-liquid chromatography using prostaglandin F1 alpha as internal standard. We found a linear negative correlation (P less than 0.001) between the amount of LDL cholesterol in the incubation solution and prostaglandin I2 synthetase activity, whereas there was a positive correlation (P less than 0.01) between HDL cholesterol and prostaglandin I2 synthesis. A very low concentration of LDL cholesterol and a high concentration of HDL cholesterol stimulated prostaglandin I2 synthesis, whereas a high LDL cholesterol concentration inhibited prostaglandin I2 biosynthesis by 64%. The concentration range of LDL and HDL cholesterol was representative of physiologically low, normal or elevated levels of lipoproteins.     

Influence of adjuvant arthritis on main urinary metabolites of prostaglandin F and E in rats

The influence of adjuvant arthritis in rats on main urinary metabolites (MUM) of prostaglandin (PG) F and E type was studied.1) In our model rats, urinary excretion of PGE-MUM increased on day 11 prior to the appearance of secondary lesions, but that of PGF-MUM did not change significantly during the observed period (21 days). The excretion of PGE-MUM was not proportional to the increase in both hind paws volume.2) Indomethacin, which diminished primary lesions but did not suppress secondary lesions, reduced the increase in urinary excretion of PGE-MUM.3) Prednisolone and azathiopurine, which suppressed both primary and secondary lesions, increased the excretion of PGE-MUM over adjuvant control values on days 4 and 8.The facts described above suggest that the increase of endogenous PGE during days 4 to 8 may be important in the suppression of secondary lesions in adjuvant arthritis in rats.     

Changes in morphine self-administration in rats induced by prostaglandin E1 and naloxone

Interactions of prostaglandin E₁ (PGE₁) with morphine have been reported in several test systems and an hypothesis has been advanced for a role of prostaglandins in morphine analgesia and physical dependence. In rats self-administering morphine intravenously, a simultaneous and continuous infusion of naloxone hydrochloride at 56 to 560 μg/kg/day caused the expected increase in injection rate for morphine. Infusion of PGE₁ by itself at 56 or 180 μg/kg/day had no effect on the rate of morphine intake. Likewise the addition of PGE₁ at 180 μg/kg/day did not potentiate the increase caused by naloxone (56 or 180 μg/kg/day) when it was added to the naloxone infusion. These results do not support a role for prostaglandins in the behavioral aspects of morphine addiction. However, larger doses of PGE₁ (1 and 1.8 mg/kg/day), which were without overt effects in normal rats, caused severe and incapacitating prostration in morphinized rats.     

Elevation of brain prostaglandin E2 levels in rodents by delta 1-tetrahydrocannabinol.

An isotopic dilution procedure using specific prostaglandin E2 (PGE2) brain receptors was utilized to determine the changes in brain PGE2 levels subsequent to drug exposure. Delta-1-tetrahydrocannabinol (delta 1-THC) stimulated PGE2 synthesis resulting in increased brain concentrations when compared with vehicle treated rats and mice. Indomethacin markedly inhibited the delta 1-THC elevated rise in PGE2 levels presumably by inhibition of prostaglandin synthetase. The delta 1-THC-induced increase in PGE2 brain levels was also suppressed by i.v. administered rabbit PGE2-antiserum. This suggests that one of the sites of delta 1-THC action is extracerebral and from here a portion of the released prostaglandins are transported to the brain. These results add further support to previous data that delta 1-THC given orally results in an increase in brain PGE2 levels.     

Effect of EGCG on lipid absorption and plasma lipid levels in rats

Catechins, compounds derived from green tea, have been shown to reduce plasma cholesterol levels and the rate of cholesterol absorption. We investigated the dose response and the mechanism of action of epigallocatechin gallate (EGCG) on these parameters in rats. Wistar rats were fed a diet high in cholesterol and fat containing either none, 0.25% (0.2 g/day/kg BW), 0.5% (0.4 g/day/kg/BW) or 1.0% (0.7 g/day/kg BW) of EGCG. After 4 weeks of treatment, total cholesterol and low density lipoprotein plasma levels were significantly reduced in the group fed 1% EGCG when compared to the no treatment group. Plasma triglycerides and high-density lipoprotein levels did not change significantly. Following a single oral application of a liquid test-meal, intestinal cholesterol absorption in Wistar rats was 79.3% in the control group. In the group treated with 0.1 g/kg BW EGCG intestinal cholesterol absorption decreased to 73.7% and in the group treated with 0.5 g/kg BW of EGCG intestinal cholesterol absorption fell significantly to 62.7% (P = 0.005). Total fat absorption was very efficient in the control group (99.5% of the applied dose) and decreased significantly but moderately in the group treated with the highest doses of EGCG (0.75, 1 g/kg BW). In an in-vitro biliary micelle model, the addition of 55 microM to 1300 microM EGCG not only decreased cholesterol solubility dose-dependently in these micelles but also altered the size of the mixed lecithin/taurocholate/cholesterol micelles as demonstrated by light scattering. This study provides evidence suggesting that the cholesterol-lowering effect of green tea is mainly elicited by EGCG, one of the most abundant catechins contained in green tea. It is suggested that one of the underlying mechanisms by which EGCG affects lipid metabolism is by interfering with the micellar solubilization of cholesterol in the digestive tract, which then in turn decreased cholesterol absorption.     

Effect of bromocriptine on lipid plasma levels in rats

Results show that bromocriptine induced marked alterations in plasma levels of cholesterol and lipids in response to acute and chronic administrations in rats. Two hours after an I.P. dose of 10 mg/kg, bromocriptine mesylate caused significant reductions in plasma levels of total high density lipoprotein (HDL) and high density lipoprotein cholesterol (HDL cholesterol). At a dose of 20 mg/kg, bromocriptine mesylate induced significant elevations in plasma levels of total cholesterol, total HDL, HDL cholesterol, total low density lipoproteins (LDL), and low density lipoprotein cholesterol (LDL cholesterol). Injected at a dose of 4 or 10 mg/kg daily for 14 consecutive days, bromocriptine mesylate caused significant increases in plasma levels of total cholesterol, LDL cholesterol and total LDL whereas the levels of HDL cholesterol, total HDL triglycerides (TG) were reduced. At a dose of 20 mg/kg all parameters were significantly increased. Marked hyperglycaemia was noticed in response to doses of 10, 15 and 20 mg/kg injected daily for 14 consecutive days or 2 hrs after a single administration of 15 mg/kg. Plasma insulin activity was reduced 2 hours after injection of bromocriptine at a dose of 15 mg/kg Likewise, a significant reduction in plasma insulin activity was observed in response to daily I.P. injections of bromocriptine at a dose of 15 mg/kg. Hyperglycaemic and hypoinsulinaemic effects of bromocriptine (acute and chronic) were markedly decreased when sulpiride, a dopaminergic D2 antagonist, was injected at an I.P. dose of 10 mg/kg before bromocriptine. Plasma ACTH activity was significantly increased in response to bromocriptine (15 mg/kg I.P.) in acute and chronic experiments. This effect was markedly diminished when sulpiride was injected prior to bromocriptine. In conclusion, bromocriptine induced marked elevations in plasma levels of total cholesterol and lipids which are likely to be related to hyperglycaemic and hypoinsulinaemic effects.     

Influence of extract of Rosa rugosa roots on lipid levels in serum and liver of rats

The effects of the methanol extract of Rosa rugosa roots on serum and liver lipids were studied in rats. The rats were fed the purified diets with or without the methanol extract at the 1% level for 4 weeks. The concentrations of serum and liver total cholesterol were not significantly affected by the feeding of extract. Feeding of the extract, on the other hand, reduced the liver triacylglycerol content without influencing the serum triacylglycerol level. The effects of the extract on lipids profiles were diminished markedly by dietary cholesterol. The results suggest an existence of component in the extract which may ameliorate the accumulation of triacylglycerol in rat liver.