Changes In Prostaglandin Metabolism Research Articles

Evening Primrose Oil and Fish Oil for Severe Chronic Mastalgia: A Randomized, Double-Blind, Controlled Trial

Recently evening primrose oil has been a popular holistic recommendation for the treatment of mastalgia because of its ability to affect prostaglandin metabolism. To investigate the ability of evening primrose oil to alleviate symptoms of mastalgia, the authors conducted a randomized, double-blind clinical trial. Fish oil was included in the study because it also is known to produce changes in prostaglandin metabolism. Control oils were corn oil and wheat germ oil, which were chosen for their common usage and similarity in color to the study oils. Participants for the study were recruited in Holland from 1993 through 1996 through an extensive publicity campaign involving general practitioners, surgeons, patient organizations, Dutch magazines, and posted advertisements. Women who enrolled in the study met these five criteria: cyclic or noncyclic mastalgia for more than 6 months, a minimum of 5 days and a median of at least 7 days of pain per menstrual cycle, age between 18 and 45 years, premenopausal state, and at least one functioning ovary. One hundred twenty women, 94 with cyclic and 26 with noncyclic mastalgia, enrolled in the study. Their mean age was 37.6 years. After the first clinical visit, all patients began keeping a daily pain diary, which included days with pain, severity of pain, and menstrual periods. At 3 months participants returned for a second evaluation. The 120 women recorded a mean number of 70.5 pain days in the 3-month period. On a scale of 1 to 3, the mean severity of pain was 1.64. At this time the patients were randomly assigned to one of four treatment groups that received daily regimens of 3 g of two different treatment oils. The first group received fish oil and control oil (FC); the second, evening primrose oil and control oil (EC); the third, fish oil and evening primrose oil (EF); and the fourth, two control oils (CC). Twelve women dropped out of the trial: eight because of adverse side effects, one for treatment failure, one because she became pregnant, and two because their symptoms had improved. Fifteen patients took fewer than the prescribed numbers of pills, including seven who took less than half of the doses. Eleven women complained of side effects, and four had difficulty taking or remembering pills. Side effects of treatments and placebos included gastric and abdominal symptoms, skin complaints, and weight gain. Women taking fish oil had the most trouble with gastric symptoms (belching, nausea, acidity, pain, fullness, and vomiting); 43% of those in the FC group and 60% of those in the EF group had these problems, compared with 20% and 27% of those in the EC and CC groups, respectively (P <.001). Other side effects were fairly evenly distributed. All patients experienced a decrease in the number of pain days. Fish oil registered a 15.5% decrease in pain days compared with 10.6% for its control oil, and evening primrose oil had a 12.3% decrease, compared with 13.8% for its control oil. The differences were not statistically significant. A slight decrease in severity of pain was reported by the women in all groups (0.06% to 0.08%).

Induction of cyclooxygenase-2 messenger RNA after transient and permanent middle cerebral artery occlusion in rats: comparison with c-fos messenger RNA by using in situ hybridization.

Recently, two different cyclooxygenase (COX) genes, COX-1 and -2, were identified. In this study, topographic and chronological profiles of COX-2 messenger (m)RNA and c-fos mRNA expression were investigated using in situ hybridization after focal cerebral ischemia. Rats undergoing permanent ischemia were decapitated at 30 and 90 minutes and at 2, 4, 8, and 24 hours after middle cerebral artery (MCA) occlusion, and rats undergoing transient ischemia were decapitated at 4, 8, and 24 hours after MCA occlusion that lasted for either 30 or 90 minutes. After brief transient MCA occlusion, c-fos mRNA was induced in the whole MCA territory, adjacent cortex (cingulate cortex), and distant brain regions such as the hippocampus and substantia nigra. In contrast, COX-2 mRNA was not induced in the ischemic core (lateral striatum) but only in the penumbral area (MCA cortex). Long transient and permanent MCA occlusion did not induce c-fos and COX-2 mRNAs in the ischemic core but strongly induced both mRNAs in the penumbral area (medial striatum and periphery of MCA cortex) and adjacent cortex (cingulate cortex). In brain regions distant from the ischemic territory, although c-fos mRNA was induced in the thalamus, substantia nigra, and hippocampus after extended transient and permanent occlusion, COX-2 mRNA was only induced in the bilateral hippocampi. The induction of COX-2 mRNA persisted in all locations even at 24 hours after MCA occlusion. The distribution of COX-2 mRNA induction was apparently different from that of c-fos mRNA after MCA occlusion. These results pertaining to COX-2 mRNA agree well with the previous observations of changes in prostaglandin metabolism induced by focal cerebral ischemia. However, whether this induction of the COX-2 gene contributes to the histopathological outcome of cerebral ischemia remains to be elucidated.

Inhibition of atherosclerosis by cod-liver oil in a hyperlipidemic swine model.

We studied the effect of cod-liver oil on the development and progression of coronary artery disease in swine subjected to coronary balloon abrasion and fed an atherogenic diet for eight months. Sections from serial 3-mm segments of the coronary arteries were analyzed morphometrically in 7 pigs given a cod-liver-oil supplement and 11 control animals not given the supplement. Significantly less disease was seen in the sections from the animals fed cod-liver oil. The mean lesion area per vessel, mean luminal encroachment per vessel, and mean maximal luminal encroachment per vessel were reduced in animals fed cod-liver oil, as compared with controls, (P = 0.05, P = 0.016, and P = 0.011, respectively). Both groups of animals had severe hyperlipidemia throughout the study. Differences in the extent of coronary atherosclerosis were not related to differences in plasma lipid levels. Platelet arachidonate was markedly reduced, platelet eicosapentaenoic acid was increased, and serum thromboxane was decreased in the oil-fed group as compared with the control group. We conclude that in our animal mode, dietary cod-liver oil retarded the development of coronary artery disease, possibly through changes in prostaglandin metabolism.

Effects of cloprostenol administration on neutral lipid and prostaglandin F metabolism by porcine luteal tissue

The effects of Cloprostenol administration on porcine luteal lipid metabolism, progesterone production, and prostaglandin F production were examined in 32 pigs at day 12 of the estrous cycle. Pigs were killed between 0 and 18 hours after treatment. Recovered luteal tissue was incubated at 0 C and at 37 C in the absence and presence of dibutyryl cyclic AMP and indomethacin. Net in vitro release of progesterone from luteal tissue was depressed within 1 hour after Cloprostenol treatment whereas net in vitro release of prostaglandin F was accelerated 4 hours after Cloprostenol treatment. Inclusion of dibutyryl cyclic AMP in the incubation media did not alter progesterone production by did enhance prostaglandin F production at 0 and 1 hour after Cloprostenol treatment. Inclusion of indomethacin in the incubation media completely inhibited the Cloprostenol-induced acceleration of in vitro luteal PGF production. Cloprostenol treatment increased luteal triglycerides and decreased luteal free cholesterol and cholesterol esters within 1 hr after treatment. Arachidonic acid percentages in free fatty acids and triglycerides were also increased within 1 hr after treatment. When 37 C and 0 C incubations were compared, in vitro luteal accumulation of free fatty acids was maximum at 1 hr after Cloprostenol treatment. In vitro accumulation of triglycerides in luteal tissie was comparatively uniform at all times examined during the first 18 hr after Cloprostenol treatment. Comparison of 37 C and 0 C incubations further revealed that luteal triglycerides were active in accumulation of arachidonic acid. Inclusion of dibutyryl cyclic AMP and/or indomethacin in the incubation media did not alter luteal lipid contents or fatty acid compositions. Blood plasma progesterone was depressed at 4 hours after Cloprostenol whereas 13,14-dihydro-15-keto-prostaglandin F2a was elevated at 18 hours after treatment. Blood plasma free fatty acids increased 330 percetn at 4 hours and free fatty acid compositions also changed at this time. In both luteal tissue and blood plasma, changes in steroid and fatty acid metabolism occurred prior to changes in prostaglandin metabolism, suggesting that Cloprostenol induced functional luteal regression prior to altering prostaglandin metabolism.

Aggregation and thromboxane formation by platelets and vascular prostacyclin production from BB rats. An animal model for type I diabetes

Atherosclerosis and thrombembolic complications occur earlier, are more severe and especially more frequent in diabetics. Platelet aggregation, thromboxane A 2 formation by platelets and vascular prostacyclin (PGI 2) production seem to play an important role in these complications. To study these processes in more detail the BB rats as an animal model for Type I diabetes was chosen, thus excluding the difficulties in interpretation of findings in man due to the heterogeneity in human diabetes. Although on daily insulin injections, these rats were strongly hyperglycemic. Platelet aggregation induced by ADP and collagen was higher in BB rats when compared with the normoglycemic Wistar controls. The production of TXB 2, the stable metabolite of TXA 2, was significantly higher after arachidonic acid or collagen exposure of platelets, however showed no significant difference to controls after ADP. PGI 2 release from aortic rings was significantly slowed down in diabetic animals. This reduction in PGI 2 could not be prevented by the addition of insulin in vitro. It is concluded that these biochemical alterations occur early in the diabetic state. It might be speculated that hyperglycemia itself causes these changes in prostaglandin metabolism and platelet aggregability by changes in carbohydrate metabolism and glycosylation of important functional and structural proteins.

Fetal 15-hydroxyprostaglandin dehydrogenase is altered by maternal ethanol exposure.

Several studies have suggested that ethanol consumption may alter prostaglandin metabolism and that this alteration may represent the molecular mechanism underlying certain of the pathophysiological consequences of chronic alcoholism. Our laboratory is investigating the hypothesis that ethanol induced changes in prostaglandin metabolism may be volved in the etiology of the condition termed fetal alcohol syndrome. In this study, pregnant rats (Holtzman) were exposed for 2 h each day throughout gestation to ethanol by vapor inhalation. Ethanol exposure resulted in retarded fetal growth and changes in the prostaglandin dehydrogenase activity in homogenates from placental amnion and maternal and fetal kidney.

Prostaglandin synthesis and inactivation in kidneys and lungs of rats with experimental diabetes.

1. Microsomal prostaglandin synthesis and tissue prostaglandin concentrations in the kidneys of rats made diabetic by pretreatment with alloxan or streptozotocin were significantly decreased but were unchanged in lungs. 2. Prostaglandin inactivation was increased in kidneys of alloxan-diabetic rats but not changed in streptozotocin-diabetic kidneys or in the lungs of either group. 3. These changes in prostaglandin metabolism may cause a renal prostaglandin deficit and could contribute to certain pathological sequelae observed in diabetes mellitus.