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Background Eicosanoids and sand fly saliva have a critical role in the Leishmania infection. Here, we evaluated the effect of Lutzomyia longipalpis salivary gland sonicate (SGS) on neutrophil and monocyte recruitment and activation of eicosanoid production in a murine model of inflammation. Methods C57BL/6 mice were inoculated intraperitonealy with Lutzomyia longipalpis SGS or Leishmania infantum or both, followed by analyses of cell recruitment, parasite load and eicosanoid production. Results Intraperitoneal injection of Lutzomyia longipalpis SGS together with Leishmania infantum induced an early increased parasite viability in monocytes and neutrophils. L. longipalpis SGS increased prostaglandin E 2 (PGE 2 ), but reduced leukotriene B 4 (LTB 4 ) production ex vivo in peritoneal leukocytes. In addition, the pharmacological inhibition of cyclooxygenase 2 (COX-2) with NS-398 decreased parasite viability inside macrophages during Leishmania infection in the presence of L. longipalpis SGS arguing that PGE 2 production is associated with diminished parasite killing. Conclusions These findings indicate that L. longipalpis SGS is a critical factor driving immune evasion of Leishmania through modulation of PGE 2 /LTB 4 axis, which may represent an important mechanism on establishment of the infection.

Peroxisome proliferator-activated receptors (PPARs) alpha and gamma are key regulators of lipid homeostasis and are activated by a structurally diverse group of compounds including fatty acids, eicosanoids, and hypolipidemic drugs such as fibrates and thiazolidinediones. While thiazolidinediones and 15-deoxy-delta(12,14)-prostaglandin J2 have been shown to bind to PPARgamma, it has remained unclear whether other activators mediate their effects through direct interactions with the PPARs or via indirect mechanisms. Here, we describe a novel fibrate, designated G2331, that is a high-affinity ligand for both PPARalpha and PPARgamma. Using GW2331 us a radioligand in competition binding assays, we show that certain mono- and polyunsaturated fatty acids bind directly to PPARalpha and PPARgamma at physiological concentrations, and that the eicosanoids 8(S)-hydroxyeicosatetraenoic acid and 15-deoxy-delta(12,14)-prostaglandin J2 can function as subtype-selective ligands for PPARalpha and PPARgamma, respectively. These data provide evidence that PPARs serve as physiological sensors of lipid levels and suggest a molecular mechanism whereby dietary fatty acids can modulate lipid homeostasis

The incidence of fluconazole-resistant Candida albicans has been increasing worldwide. Both biofilm and fungal morphogenesis are main virulence factors of C. albicans cells. Extracellular fungal prostaglandins are synthesized during biofilm adhesion and development and through yeast-hypha conversion. Hence, we targeted prostaglandin synthesis with various cyclooxygenase (COX) inhibitors (aspirin, diclofenac, ketoprofen, tenoxicam, and ketorolac) and assessed their effect on fungal adhesion, biofilm formation, and yeast-hypha conversion in clinical isolates of Fluconazole resistant C. albicans. Significant reduction in fungal adhesion and detachment of mature biofilm was attained down to 1 mM concentrations of anti-inflammatory agents. Microscopical examination of fungal cells in the presence of the tested drugs showed significant reduction of germ tube formation. Therefore, COX inhibitors have a significant effect on reduction of Candida adhesion and biofilm development in correlation with fungal morphogenesis. Moreover, inhibition of C. albicans by COX inhibitors gave synergistic activity with fluconazole suggesting that combination therapeutic strategies may be fruitful for management of infection of Fluconazole resistant C. albicans.

Prostaglandins are involved in the reproductive processes in a variety of animals, including crustaceans. It was found that polychaetes, the best maturation diet for shrimp broodstock, possessed the greatest variation of prostaglandin Esub(2) (PGEsub(2)) when compared with other live feeds. The level of PGEsub(2) varied according to sizes, feed intake, sources and type of polychaete. The matured and also larger sand polychaete Perinereis sp. contained higher PGEsub(2) levels than younger and smaller sand polychaetes (18.16+-5.82 ng PGEsub(2)/mg protein for polychaetes at an average length of 10 cm up to 160.8+-37.09 ng PGEsub(2)/mg protein for polychaetes at an average length of 17 cm). The PGEsub(2) levels in ovaries and haemolymph of female shrimp fluctuated with the developmental stage of the ovaries. The highest concentration of PGEsub(2) in haemolymph was at stage 3 of ovarian development, whereas the highest concentration of PGEsub(2) in shrimp ovaries was at stage 4. In vitro incubation of Penaeus monodon pre-vitellogenic oocytes with polychaete extract and synthetic PGEsub(2) demonstrated that both PGEsub(2)s enhanced oocyte development, especially during late development and ovulation. The putative role of PGEsub(2) from polychaetes or the presence of PGEsub(2) in polychaetes may be a factor in their role as a dietary constituent required for shrimp oocyte development.

Oxidative stress and inflammation are supposed to be the key players of several acute and chronic diseases, and also for progressive aging process. Eicosanoids, especially prostaglandin F∧2α (PGF∧2α) and F₂-isoprostanes are endogenous compounds that are involved both in physiology and the above mentioned pathologies. These compounds are biosynthesized mainly from esterified arachidonic acid through both enzymatic and non-enzymatic free radical-catalysed reactions in vivo, respectively. They have shown to possess potent biological activities in addition to their application as biomarkers of oxidative stress and inflammation. Recent advancement of methodologies has made it possible to quantify these compounds more reliably and apply them in various in vivo studies successfully. Today, experimental and clinical studies have revealed that both PGF∧2α and F₂-isoprostanes are involved in severe acute or chronic inflammatory conditions such as rheumatic diseases, asthma, risk factors of atherosclerosis, diabetes, ischemia-reperfusion, septic shock and many others. These evidences promote that assessment of bioactive PGF∧2α and F₂-isoprostanes simultaneously in body fluids offers unique non-invasive analytical opportunity to study the function of these eicosanoids in physiology, oxidative stress-related and inflammatory diseases, and also in the determination of potency of various radical scavengers, anti-inflammatory compounds, drugs, antioxidants and diet.

Background and Objectives: Prostaglandin E2 (PGE2) is present in gingival crevicular fluid the (GCF) and is evidenced in periodontal disease (PD). However, there are no enough reports to correlate the PGE2 concentrations in GCF in periodontal health and disease with clinical and radiographic indicators, age and gender. Hence, the present study is aimed to estimate the levels of PGE2 in GCF of subjects without periodontal disease (SEP) and periodontal disease (CEP). Materials and Methods: 99 subjects were selected, 33 without PD (G1) and 66 with PD, 33 with gingivitis (G2) and 33 with periodontitis (G3), which were submitted to a clinical and radiographic diagnosis, registering samples FGC, being stored, centrifuged and refrigerated for preservation. Subsequently the concentration of crevicular PGE2 was measured by using the enzyme linked immunosorbent assay (ELISA), determining the concentration of each subject. Results: PGE2 was detected in all the samples. The G1 presented a concentration of 28.82 ± 2.88 pg / mL, G2 44.91 ± 4.37 pg / mL and G3 148.67 ± 74.74 pg / mL (p <0.0001). PGE2 levels were significantly correlated with bleeding on probing, probing depth, attachment loss and bone loss (p <0.05). PGE2 levels were modified by age, but not gender. Conclusion: It is well known that activated inflammatory cells produce inflammatory mediators that stimulate the production of PGE2. The findings of this study demonstrate an increased concentration of PGE2 in FCG according to the presence of greater severity of PD. PGE2 may be considered as a biomarker in PD progression. However, controlled, longitudinal studies are needed to confirm this possibility.

equine gastric ulcer syndrome (EGUS) has a multifactorial nature and it affects both the squamous and glandular mucosa of the stomach. Multiple therapeutic strategies involving large periods of medication are used to treat this condition. Objective: to evaluate the effects of administering corn oil (CO) to horses with induced gastric ulcers, and to describe the mechanism of action of the mucosal repair. Methods: fifteen horses divided into three groups were used. A combination of confinement and phenylbutazone was used during the ulcer-induction phase. After the gastroscopic evaluation and laboratory tests, animals were treated with sucralfate (SA; group I), and CO at doses of 70 and 90 mL/100 Kg (groups II and III, respectively). Gastroscopy, gastric content collection, and biopsy of the glandular mucosa were performed to analyze prostaglandin E2 (PGE2), pH, and antioxidant and oxidant parameters. Results: mild to moderate gastric lesions were induced in the glandular and non-glandular mucosa. Among the mechanisms of the treatments, reestablishment of the antioxidant parameters and inhibition of myeloperoxidase (MPO) oxidant enzyme were prominent, but PGE2 concentration had a weak influence. Conclusion: similarly to SA, CO only had therapeutic effects in the glandular mucosa.

Altered oxidative stress has long been observed in cancer cells, and this biochemical property of cancer cells represents a specific vulnerability that can be exploited for therapeutic benefit. The major role of an elevated oxidative stress for the efficacy of molecular targeted drugs is under investigation. Menadione is considered an attractive model for the study of oxidative stress, which can induce apoptosis in human leukemia HL-60 cell lines. Prostaglandin E₂ (PGE₂) via its receptors not only promotes cell survival but also reverses apoptosis and promotes cancer progression. Here, we present evidence for the biological role of PGE₂ as a protective agent of oxidative stress-induced apoptosis in monocytic cells. Pretreatment of HL-60 cells with PGE₂ markedly ameliorated the menadione-induced apoptosis and inhibited the degradation of PARP and lamin B. The EP₂ receptor antagonist AH6809 abrogated the inhibitory effect of PGE₂, suggesting the role of the EP₂/cAMP system. The PKA inhibitor H89 also reversed apoptosis and decreased the PKA activity that was elevated 10-fold by PGE₂. The treatment of HL-60 cells with NAC or zinc chloride showed a similar protective effect as with PGE₂ on menadione-treated cells. Furthermore, PGE₂ activated the Ras/Raf/MEK pathway, which in turn initiated ERK activation, and ultimately protected menadione-induced apoptosis. These results imply that PGE₂ via cell survival pathways may protect oxidative stress-induced apoptosis in monocytic cells. This study warrants further pre-clinical investigation as well as application towards leukemia clinics.