6-ketoprostaglandin F1 Alpha Synthesis Research Articles

Aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process in rats.

Aspirin, one of the most widely used drugs in the world, consistently produces gastric mucosal injury, but the pathogenic mechanisms are incompletely understood. The present study was designed to determine the role of neutrophils in aspirin-induced acute gastric mucosal injury. Gastric mucosal lesions induced by acidified aspirin (300 mg/kg) were completely prevented in rats that had been rendered profoundly neutropenic by anti-neutrophil serum. Aspirin-induced acute gastric mucosal lesions were also significantly, albeit incompletely, reduced in rats that had been rendered moderately neutropenic by methotrexate. Moreover, in the methotrexate-induced neutropenia model, the neutropenia-associated mucosal protection against aspirin-induced injury could be reversed by leucovorin rescue. Aspirin caused a marked and statistically significant reduction in gastric mucosal 6-ketoprostaglandin F1 alpha synthesis, but no significant changes in gastric mucosal leukotriene synthesis. Thus no gastric mucosal lesions were observed in profoundly neutropenic rats that were treated with aspirin, despite the marked inhibition of prostaglandin synthesis. These findings demonstrate that aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process.

Effect of high-dose methylprednisolone and U74006F on eicosanoid synthesis after subarachnoid hemorrhage in rats.

Free radicals and lipid peroxidation of membrane fatty acids are thought to play a role in the pathogenesis of arterial vasospasm and the physiopathologic patterns of neuronal damage after subarachnoid hemorrhage. We have evaluated the effects of treatment with either high-dose methylprednisolone every 8 hours or a single dose of U74006F on the temporal profile of ex vivo synthesis of four selected eicosanoids in brain slices after experimental induction of subarachnoid hemorrhage in rats. Prostaglandins D2 and E2, prostacyclin and leukotriene C4 levels were determined by radioimmunoassay after 1-hour incubation of the brain slices. The synthesis of prostaglandin D2 and 6-ketoprostaglandin F1 alpha at 48 hours after subarachnoid hemorrhage was significantly higher when compared to sham-operated animals (p = 0.01); prostaglandin E2 release was significantly enhanced at 6 hours after subarachnoid hemorrhage (p = 0.01). The release of the lipoxygenase metabolite was significantly enhanced at 1, 6, and 48 hours after subarachnoid hemorrhage induction. Both treatment regimens significantly reduced the ex vivo synthesis of prostaglandin D2, prostaglandin E2, and leukotriene C4 at 1, 6, and 48 hours after subarachnoid hemorrhage, whereas the effects on 6-ketoprostaglandin F1 alpha synthesis differed in the two treatment groups. U74006F enhanced the synthesis of prostacyclin metabolite in the early phase after subarachnoid hemorrhage, and high-dose methylprednisolone reduced the increasing synthesis at 48 hours. A strict comparison between the two treatments was not possible because of the different modalities of administration. However, these data suggest that the antioxidant effect of single-dose treatment with U74006F influenced the early and delayed effects on enzymatic lipid peroxidation, whereas the effects of methylprednisolone administration every 8 hours were more significant in the delayed phase.

Potassium load prevents the decrease of GFR induced by captopril in sodium-depleted rats

Captopril decreases the glomerular filtration rate (GFR) in Na-depleted rats and inhibits the stimulation of glomerular prostanoid synthesis induced by Na depletion. Because K loading stimulates glomerular prostanoid production in normal rats, we studied the effects of K loading in Na-depleted captopril-treated (LNC) rats. Potassium, but not Cl, loading stimulated the glomerular synthesis of 6-ketoprostaglandin F1 alpha (PGF1 alpha) and thromboxane B2 (TxB2). Urinary kallikrein-like activity (UKALLV) and plasma aldosterone increased in K-loaded animals. LNC rats had lower clearances of inulin (CIN) and p-aminohippurate (CPAH) than controls (0.22 +/- 0.02 vs. 0.94 +/- 0.07 and 0.56 +/- 0.12 vs. 2.23 +/- 0.23 ml.min-1.100 g body wt-1, both P less than 0.01). KCl-loaded LNC rats had CIN and CPAH greater than LNC (0.64 +/- 0.16 and 1.90 +/- 0.28 ml.min-1.100 g body wt-1, P less than 0.01). Similar results were observed in LNC rats loaded with a K solution not containing Cl, but not in LNC rats loaded with a mixture of CaCl2, MgCl2, and HCl. In KCl-loaded LNC rats, cyclooxygenase inhibition decreased CIN from 0.49 +/- 0.09 to 0.30 +/- 0.08 ml.min-1.100 g body wt-1 (P less than 0.01). Aprotinin did not affect renal function despite significant decrease of UKALLV. We conclude that K loading prevents the decrease of GFR induced by captopril in Na-depleted rats and that this might be mediated by stimulation of glomerular prostanoid synthesis.

Ontogeny of 6-keto-PGF1 alpha synthesis in rabbit aorta and the effect of premature weaning.

A systematic study of the ontogeny of aortic 6-ketoprostaglandin F1 alpha synthesis from birth to adult life and the effect of premature weaning on this process was investigated in rabbits. Prostacyclin (PGI2) synthesis by both endogenous and exogenous arachidonic acid and its relation to aortic arachidonic acid content was determined. It was found that 1) PGI2 synthesis from endogenous arachidonic acid increased with age, whereas 2) PGI2 synthesis from exogenous arachidonic acid decreased. This correlated with a decrease in the incorporation of [14C]arachidonic acid into phospholipids with age. Aortic arachidonic acid concentration did not change from birth until 3 wk of life but increased markedly by 5 wk of age. Premature weaning caused a decrease in the synthesis of aortic PGI2 and in aortic arachidonic acid concentration initially, but the changes did not persist in later life. These studies suggest that the utilization of exogenous arachidonic acid by aorta decreases after birth perhaps due to maturity of the enzyme systems that synthesize and utilize endogenous substrates.