Prostaglandin E2 Content Research Articles

Effect of hCG and eCG Treatments on Prostaglandins Synthesis in the Porcine Oviduct

The oviduct plays a crucial role in fertilization, gamete maturation and embryo transport. Prostaglandins are some of the main factors determining its roles. The present study investigated the influence of oestrus synchronization and superovulation on prostaglandins synthesis in the porcine oviduct. Mature cross-bred gilts after exhibiting oestrous cycles were divided into four groups: I, cyclic; II, inseminated; III, synchronized and inseminated; and IV, superovulated and inseminated. Oviducts were collected on the third day of the oestrous cycle or after insemination and divided into isthmus and ampullary parts. This study demonstrated lower mRNA (in the isthmus and ampulla; p<0.05, p<0.001, respectively) and protein prostaglandin endoperoxide synthase 2 expression (in the isthmus; p<0.001) in gilts treated with human chorionic gonadotrophin/equine chorionic gonadotrophin (hCG/eCG) compared with Group II that were inseminated only. In addition, hCG and eCG treatment decreased mPGES-1 mRNA levels in Groups III and IV, in both the isthmus (p<0.01 in III, p<0.001 in IV) and ampulla (p<0.001). The prostaglandin E2 content of oviductal tissues was significantly lower in Groups III (p<0.05) and IV (p<0.01 in isthmus, p<0.0001 in ampulla) compared with Group II. mRNA and protein levels of PGFS in Group IV in the oviductal isthmus were higher (p<0.01) compared with the non-treated Group II. In effect, the amount of prostaglandin F2α in oviductal tissues of gilts treated with hCG/eCG was significantly elevated (p<0.001 in isthmus of Groups III and IV; p<0.05 in ampulla of Group IV). Differential expression of the factors analysed in gilts treated with exogenous gonadotrophins suggests that hCG/eCG stimulation affects prostaglandins synthesis pathway. These changes can alter oviduct functions and in turn affect gamete maturation and fertilization as well as development of embryos and their transport to the uterus.

Comparison of the effects of ibuprofen and acetaminophen on PGE2 levels in the GCF during orthodontic tooth movement: a human study

BackgroundPain is among the most cited negative effects of orthodontic treatment. Non-steroidal anti-inflammatory drugs seem to be an effective option for minimizing this but can have adverse effects on tooth movement owing to their ability to block prostaglandin synthesis. Acetaminophen has been suggested as the analgesic of choice during orthodontic treatment as it showed no effect on orthodontic tooth movement in previous animal studies. The purpose of this study was to compare the effects of ibuprofen and acetaminophen on the prostaglandin E2 (PGE2) levels of the gingival crevicular fluid (GCF) during orthodontic tooth movement in human subjects.MethodsA total of 42 patients (mean age 18 ± 4.5 years) were randomly divided into three equal groups: ibuprofen, acetaminophen, and control groups. Maxillary canines were distalized with 150 g of force delivered by NiTi coil springs. GCF samples were obtained before (baseline) and after spring activation at 24, 48, and 168 h. The PGE2 content of the GCF was determined using enzyme-linked immunosorbent assay.ResultsPGE2 levels in all groups increased significantly by 24 and 48 h of force application and decreased to baseline levels by 168 h. No significant difference was found between the acetaminophen and control groups at any time point. There was a significant decrease in PGE2 levels in the ibuprofen group at 24 and 48 h when compared to the other two groups.ConclusionsAcetaminophen showed no significant effect on prostaglandin synthesis and may be the safe choice compared to ibuprofen for relieving pain associated with orthodontic tooth movement.

Acute toxicity and gastroprotection studies with a newly synthesized steroid.

BackgroundSynthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3′H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats.Methodology/Principal FindingRats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE2) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE2 as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes.Conclusion/SignificanceThe current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent.

Response to 'TNF/TNFR signal transduction pathway-mediated anti-apoptosis and anti-inflammatory effects of sodium ferulate on IL-1β-induced rat osteoarthritis chondrocytes in vitro'

Sodium ferulate (SF) is a natural component of traditional Chinese herbs. Our previous study shows that SF has a protective effect on osteoarthritis (OA). The objective of this study was to investigate the effect of SF on the TNF/TNF receptor (TNFR) signal transduction pathway of rat OA chondrocytes.Primary rat articular chondrocytes were co-treated with IL-1β and SF. Chondrocyte apoptosis was assessed by fluorescein isothiocyanate-annexin V/propidium iodide assay. The PCR array was used to screen the expression of 84 key genes involved in apoptosis. The release of TNFα and prostaglandin E2 were analyzed by ELISA. Expressions of proteins were assessed by western blotting. The activity of NF-κB was determined by electrophoretic mobility shift assay (EMSA). Gene expression of inducible nitric oxide synthase (iNOS) was evaluated by real-time quantitative PCR. The nitric oxide content was measured with the Griess method.After treatment with SF, the apoptosis rate of chondrocytes significantly attenuated (P < 0.01). Results of the apoptosis PCR array suggested that mRNA expression of some core proteins in the TNF/TNFR pathway showed valuable regulation. The protein expressions of TNFα, TNFR-1, TNF receptor-associated death domain, caspase-8 and caspase-3 were prevented by SF in a concentration-dependent manner. SF also inhibited activities of caspase-8 and caspase-3 compared with the OA model control (P < 0.01). TNF receptor-associated factor-2 expression, phosphorylations of inhibitor of NF-κB kinase (IKK) subunits alpha and beta, and NF-κB inhibitor, alpha (IκBα) were all concentration-dependently suppressed by SF treatment. The results of EMSA showed that SF inhibited the activity of NF-κB. In addition, the expressions of cycloxygenase-2 and iNOS and the contents of prostaglandin E2 and NO were attenuated with the treatment of SF (P < 0.01).SF has anti-apoptosis and anti-inflammatory effects on an OA model induced by IL-1β in vitro, which were due to inhibitory actions on the caspase-dependent apoptosis pathway and the IKK/NF-κB signal transduction pathway of the TNF/TNFR pathway.

Effect of Electroacupuncture Intervention on Expression of CGRP, SP, COX-1, and PGE2 of Dorsal Portion of the Cervical Spinal Cord in Rats with Neck-Incision Pain

The present study was aimed to determine if cervicospinal substance P (SP) and its neurokinin-1 receptor (NK-1R), calcitonin gene-related peptide (CGRP), cyclooxygenase-1 (COX-1), and prostaglandin E2 (PGE2) were involved in electroacupuncture (EA) analgesia in neck-incision pain rats. EA intervention was applied to bilateral Futu (LI18), Hegu (LI4)-Neiguan (PC6), and Zusanli (ST36)-Yanglingquan (GB34) for 30 min. Cervicospinal SP and CGRP immunoactivity was detected by immunofluorescence technique, NK-1R and COX-1 protein and mRNA expression levels were determined using Western blot and real-time PCR, respectively, and PGE2 content was measured using ELISA. Outcomes indicated that EA of EA-LI18 and LI4-PC6 (not ST36-GB34) significantly suppressed neck-incision induced decrease of thermal pain threshold (P < 0.05). EA stimulation of LI18 and LI4-PC6 markedly inhibited neck-incision induced upregulation of SP and CGRP immunoactivity, NK-1 R and COX-1 mRNA and protein expression levels, as well as the increase of PGE2 content in the dorsal cervicospinal cord (P < 0.05). These findings showed that LI18 and LI4-PC6 EA stimulation-induced downregulation of SP, CGRP, NK-1R, COX-1, and PGE2 levels in the dorsal cervicospinal cord may contribute to their effects in relieving neck-incision pain. This study highlights the targets of EA intervention for reducing post-thyroid-surgery pain for the first time.

Pure tocotrienol concentrate protected rat gastric mucosa from acute stress-induced injury by a non-antioxidant mechanism

Stress has been implicated as a risk factor of various major health problems, such as stress-induced gastric mucosal injury. This study was performed to investigate the action of a pure preparation of tocotrienol (T3) concentrate, made up of 90% δ-tocotrienol and 10% γ-tocotrienol, on gastric injury of rats induced by water-immersion restraint stress (WIRS). Fourteen male Sprague-Dawley rats (200-250 g) were divided into two equal groups: a control group and a treated group. The treatment group received T3 concentrate at 60 mg/kg body weight daily for 28 days. The body weights of rats were recorded daily before the treatment was given. At the end of the treatment period, all rats were subjected to WIRS for 3.5 hours, following which the rats were euthanized. The stomachs were isolated and opened along the greater curvature for the examination of lesions and measurements of gastric malondialdehyde (MDA) and prostaglandin E₂ (PGE₂) contents. The mean gastric mucosal lesion index in the treated rats was significantly lower than that in the control rats. This suggests that the T3 concentrate has the ability to confer protection to the gastric mucosa against gastric injury induced by acute stress. No significant difference was observed for changes in body weight before and after the treatment. The gastric PGE2 content in both groups was comparable. However, the gastric MDA content was significantly higher in the treated group compared to the control group, indicating that the T3 supplementation was not able to reduce the lipid peroxidation process. This study concludes that the T3 concentrate has the ability to protect the gastric mucosa from stress-induced injury by a non-antioxidant mechanism.

Anti-inflammatory, antioxidative and matrix metalloproteinase inhibitory properties of 20(R)-ginsenoside Rh2 in cultured macrophages and keratinocytes

This work aimed to assess the matrix metalloproteinase inhibitory and related pharmacological actions of 20(R)-ginsenoside Rh2 (20(R)-Rh2) in cultured macrophages and keratinocytes. In-vitro anti-inflammatory activity of 20(R)-Rh2 was evaluated by analysing nitric oxide (NO) and prostaglandin E2 (PGE2) contents in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Its antioxidant activity was determined by measuring the level of reactive oxygen species (ROS) in the macrophage and keratinocyte cells. Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) activity in the culture medium was detected using zymography. 20(R)-Rh2 was able to suppress NO, PGE2, ROS and pro-matrix metalloproteinase-9 (pro-MMP-9) levels that were enhanced in the LPS-stimulated murine RAW264.7 macrophage cells. 20(R)-Rh2 also exhibited inhibitory effects on the level of ROS and the activity of MMP-9 and -2 in human HaCat keratinocyte cells without stimulant exposure. 20(R)-Rh2 could suppress the gelatinolytic activity of MMP-9 enhanced by tumour necrosis factor-α in the keratinocytes. 20(R)-Rh2, a minor stereoisomer of ginsenoside Rh2, possesses matrix metalloproteinase inhibitory, anti-inflammatory and antioxidative activity.

Potential Gastroprotective Effect of Novel Cyperenoic Acid/Quinone Derivatives in Human Cell Cultures

The stem bark of Tabebuia species and the rhizomes of Jatropha isabelii are used in Paraguayan traditional medicine to treat gastric lesions and as anti-inflammatory agents. The sesquiterpene cyperenoic acid obtained from J. isabelii has been shown to display a gastroprotective effect in animal models of induced gastric ulcers while the quinone lapachol shows several biological effects associated with the use of the crude drug. The aim of this work was to prepare hybrid molecules presenting a terpene and a quinone moiety and to obtain an assessment of the gastroprotective activity of the new compounds using human cell cultures (MRC-5 fibroblasts and AGS epithelial gastric cells). Eight compounds, including the natural products and semisynthetic derivatives were assessed for proliferation of MRC-5 fibroblasts, protection against sodium taurocholate-induced damage, prostaglandin E2 content, and stimulation of cellular-reduced glutathione synthesis in AGS cells. The following antioxidant assays were performed: DPPH discoloration, scavenging of the superoxide anion, and inhibition of induced lipoperoxidation in erythrocyte membranes. 3-Hydroxy-β-lapachone (3) and cyperenoic acid (4) stimulated fibroblast proliferation. Lapachol (1), dihydroprenyl lapachol (2), 3-hydroxy-β-lapachone (3), and lapachoyl cyperenate (6) protected against sodium taurocholate-induced damage in AGS cells. Lapachol (1) and dihydroprenyl lapachoyl cyperenate (7) significantly stimulated prostaglandin E2 synthesis in AGS cells. Compounds 3, 4, and 7 raised reduced glutathione levels in AGS cells. The hybrid compounds presented activities different than those of the starting sesquiterpene or quinones.

Therapeutic effect of nux vomica total alkali gel on adjuvants arthritis rats

To observe the therapeutic effect and mechanism of nux vomica total alkali gel (NVTAG) on adjuvants arthritis (AA) rats. SD rats were randomly divided into nine groups: the normal group, the AA model group, NVTAG high, middle and low-dose (25, 12.5, 6.25 mg x kg(-1)) groups and the Votalin control (diclofenac diethylamine emulgel, 50 mg x kg(-1)) group. Except for the normal group, the remaining groups were transcutaneously administered with 0.1 mL freund's adjuvant complete (FCA) for inflammation in left rear feet and then evenly treated with medicine and packed with oilpapers. The foot volume method was adopted to determine foot swelling degree, with pain scoring and polyarthritis scoring. HE staining was used to observe arthro-pathologic injury. The content of prostaglandin E2 (PGE2), interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF-alpha) and vascular epidermal growth factor (VEGF) in synovium homogenates were measured by enzyme-linked immuno-absorbent assay (ELISA) respectively. Compared with the model group, NVTAG and control gel can obviously reduce the foot swelling degree, polyarthritis indicators and relieve arthro-pathologic injury in AA rats (17-21 d). The levels of IL-1, PGE2, IL-6, VEGF and TNF-alpha in synovial homogenates of AA rats were also reduced by NVTAG significantly. NVTAG shows an antergic effect on AA progress in rats, which is closely related to inhibition of development of inflammatory mediator.

Ethanol consumption enhances periodontal inflammatory markers in rats

ObjectiveThe aim of this study was to assess the short term effect of ethanol administration on periodontal disease in rats. DesignRats received either ethanol 2g/kg or water by gastric gavage twice a day. On the fifth day ligatures were tied around the molars of half of the rats to induce periodontitis. After 7days gingival tissue was removed and assayed for inflammatory markers. Finally, hemi-mandibles were extracted to evaluate bone loss by histomorphometrical techniques. ResultsThe experimental periodontitis increased significantly the mRNA expression (p<0.001) and activity (p<0.001) of inducible nitric oxide synthase (iNOS) in the gingival tissue, whilst short time ethanol administration increased iNOS activity (p<0.05) and produced an additive effect on iNOS mRNA expression augmented by periodontitis (p<0.01). The short time ethanol administration also potentiated the periodontitis stimulatory effect on the mRNA expression of interleukin (IL)-1β (p<0.01 and p<0.001, in semi-quantitative and real time PCR, respectively) and on the height of periodontal ligament (p<0.05). However, the ligature-induced periodontitis, but not ethanol administration, increased the prostaglandin E2 content (p<0.05) and, diminished the alveolar bone volume (p<0.05), as compared to sham rats. ConclusionThe present results suggest that ethanol consumption could represent a risk indicator for periodontal disease since augments the expression of inflammatory markers, in healthy rats, and increases them, at short term, during the illness. However, scale longitudinal investigation and more case–control studies are needed to confirm this statement.

Protective and Therapeutic Effects of Argyreia speciosa against Ethanol-Induced Gastric Ulcer in Rats

The protective and therapeutic effects of Argyreia speciosa Sweet (Convolvulaceae) against ethanol-induced gastric ulcer in rats were evaluated. Ethanolic and water extracts of the aerial plant parts (200 mg/kg body weight) were orally administered daily for seven days prior to or after ulceration with one oral dose of 1 mL absolute ethanol on 24-h empty stomachs. Rats were divided into eleven groups. Group 1 served as control. To groups 2 and 3 each extract was administered. Groups 4 to 6 received each extract or ranitidine (100 mg/kg body weight) prior to ulcer induction. Groups 7 to 9 received each extract or ranitidine post ulcer induction. Groups 10 and 11 were gastric ulcerative rats after one hour and one week of ethanol induction. The evaluation was done through measuring ulcer indices: stomach acidity and volume, lesion counts, mucus, and prostaglandin E2 contents. Oxidative stress marker, i. e. malondialdehyde, glutathione, and superoxide dismutase, were estimated. Certain marker enzymes for different cell organelles, i. e. succinate and lactate dehydrogenases, glucose-6-phosphatase, acid phosphatase, and 5'-nucleotidase, were evaluated. The work was extended to determine the collagen content and the histopathological assessment of the stomach. Gastric ulcer exhibited a significant elevation of the ulcer index, antioxidant levels, collagen content, and the marker enzymes. The water extract attenuated these increments and was more potent as a protective agent, while the ethanol extract exhibited stronger therapeutic potency. In conclusion, A. speciosa acted as antiulcer agent. More detailed studies are required to identify the compounds responsible for the pharmacological effect.

TNF/TNFR signal transduction pathway-mediated anti-apoptosis and anti-inflammatory effects of sodium ferulate on IL-1β-induced rat osteoarthritis chondrocytes in vitro

IntroductionSodium ferulate (SF) is a natural component of traditional Chinese herbs. Our previous study shows that SF has a protective effect on osteoarthritis (OA). The objective of this study was to investigate the effect of SF on the TNF/TNF receptor (TNFR) signal transduction pathway of rat OA chondrocytes.MethodsPrimary rat articular chondrocytes were co-treated with IL-1β and SF. Chondrocyte apoptosis was assessed by fluorescein isothiocyanate-annexin V/propidium iodide assay. The PCR array was used to screen the expression of 84 key genes involved in apoptosis. The release of TNFα and prostaglandin E2 were analyzed by ELISA. Expressions of proteins were assessed by western blotting. The activity of NF-κB was determined by electrophoretic mobility shift assay (EMSA). Gene expression of inducible nitric oxide synthase (iNOS) was evaluated by real-time quantitative PCR. The nitric oxide content was measured with the Griess method.ResultsAfter treatment with SF, the apoptosis rate of chondrocytes significantly attenuated (P < 0.01). Results of the apoptosis PCR array suggested that mRNA expression of some core proteins in the TNF/TNFR pathway showed valuable regulation. The protein expressions of TNFα, TNFR-1, TNF receptor-associated death domain, caspase-8 and caspase-3 were prevented by SF in a concentration-dependent manner. SF also inhibited activities of caspase-8 and caspase-3 compared with the OA model control (P < 0.01). TNF receptor-associated factor-2 expression, phosphorylations of inhibitor of NF-κB kinase (IKK) subunits alpha and beta, and NF-κB inhibitor, alpha (IκBα) were all concentration-dependently suppressed by SF treatment. The results of EMSA showed that SF inhibited the activity of NF-κB. In addition, the expressions of cycloxygenase-2 and iNOS and the contents of prostaglandin E2 and NO were attenuated with the treatment of SF (P < 0.01).ConclusionSF has anti-apoptosis and anti-inflammatory effects on an OA model induced by IL-1β in vitro, which were due to inhibitory actions on the caspase-dependent apoptosis pathway and the IKK/NF-κB signal transduction pathway of the TNF/TNFR pathway.

Mechanisms of Gastroprotective Effects of Ethanolic Leaf Extract ofJasminum sambacagainst HCl/Ethanol-Induced Gastric Mucosal Injury in Rats

Jasminum sambac is used in folk medicine as the treatment of many diseases. The aim of the present investigation is to evaluate the gastroprotective effects of ethanolic extracts of J. sambac leaves against acidified ethanol-induced gastric ulcers in rats. Seven groups of rats were orally pre-treated with carboxymethylcellulose (CMC) as normal group, CMC as ulcer group, 20 mg/kg of omeprazole as positive group, 62.5, 125, 250, and 500 mg/kg of extract as the experimental groups, respectively. An hour later, CMC was given orally to normal group and acidified ethanol solution was given orally to the ulcer control, positive control, and the experimental groups. The rats were sacrificed after an hour later. Acidity of gastric content, the gastric wall mucus, ulcer areas, and histology and immunohistochemistry of the gastric wall were assessed. Gastric homogenates were determined for prostaglandin E2 (PGE2), superoxide dismutase (SOD), andmalondialdehyde (MDA) content. Ulcer group exhibited significantly severe mucosal injury as compared with omeprazole or extract which shows significant protection towards gastric mucosal injury the plant promotes ulcer protection as it shows significant reduction of ulcer area grossly, and histology showed marked reduction of edema and leucocytes infiltration of submucosal layer compared with ulcer group. Immunohistochemistry showed overexpression of Hsp70 protein and downexpression of Bax protein in rats pretreated with extract. Significant increased in the pH, mucus of gastric content and high levels of PGE2, SOD and reduced amount of MDA was observed.

Flavocoxid, a dual inhibitor of COX-2 and 5-LOX of natural origin, attenuates the inflammatory response and protects mice from sepsis.

IntroductionCecal ligation and puncture (CLP) is an inflammatory condition that leads to multisystemic organ failure. Flavocoxid, a dual inhibitor of cyclooxygenase (COX-2) and 5-lipoxygenase (5-LOX), has been shown in vitro to possess antiinflammatory activity in lipopolysaccharide (LPS)-stimulated rat macrophages by reducing nuclear factor (NF)-κB activity and COX-2, 5-LOX and inducible nitric oxide synthase (iNOS) expression. The aim of this study was to evaluate the effects of flavocoxid in a murine model of CLP-induced polymicrobial sepsis.MethodsC57BL/6J mice were subjected to CLP or sham operation. In a first set of experiments, an intraperitoneal injection of flavocoxid (20 mg/kg) or vehicle was administered 1 hour after surgery and repeated every 12 hours. Survival rate was monitored every 24 hours throughout 120 hours. Furthermore, additional groups of sham and CLP mice were killed 18 hours after surgical procedures for blood-sample collection and the lung and liver were collected for biomolecular, biochemical and histopathologic studies.ResultsCOX-2, 5-LOX, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, extracellular-regulated-kinase 1/2 (ERK), JunN-terminal kinase (JNK), NF-κB, and β-arrestin 2 protein expression were evaluated in lung and liver with Western blot analysis. In addition, leukotriene B4 (LTB4), prostaglandin E2 (PGE2), cytokines, and lipoxin A4 serum content were measured with an enzyme-linked immunosorbent assay (ELISA). Flavocoxid administration improved survival, reduced the expression of NF-κB, COX-2, 5-LOX, TNF-α and IL-6 and increased IL-10 production. Moreover, flavocoxid inhibited the mitogen-activated protein kinases (MAPKs) pathway, preserved β-arrestin 2 expression, reduced blood LTB4, PGE2, TNF-α and IL-6, and increased IL-10 and lipoxin A4 serum levels. The treatment with flavocoxid also protected against the histologic damage induced by CLP and reduced the myeloperoxidase (MPO) activity in the lung and liver.ConclusionsFlavocoxid protects mice from sepsis, suggesting that this dual inhibitor may represent a promising approach in such a life-threatening condition.

Effect of plaunotol on gastric injury induced by ischaemia-reperfusion in rats.

Plaunatol, an anti-ulcer drug, increases prostaglandin content in gastric tissue but its effect on radical-mediated gastric damage or activity against reactive oxygen species is unknown. We examined the effects of oral administration of plaunotol (Kelnac) on the acute gastric mucosal lesion and its progression to ulcer lesion induced by ischaemia-reperfusion in rats. Plaunotol (30 and 100 mg kg-1, 15 min before ischaemia) significantly reduced the total erosion area observed immediately after ischaemia-reperfusion. When plaunotol (30 and 100 mg kg-1, once a day) was administrated orally 60 min after reperfusion, it prevented the progression from erosion to ulcer. At 72 h after ischaemia-reperfusion, the total area of ulcers lesions was significantly reduced compared with that without plaunotol administration. Furthermore, treatment with plaunotol (100 mg kg-1) significantly increased prostaglandin E2 content in gastric tissues of both acute gastric mucosal lesion and gastric ulcer lesion. In in-vitro experiments, plaunotol (1-3 mg mL-1) reduced the superoxide radicals generated by leucocytes, but not by xanthine oxidase. These results indicate that plaunotol has protective effects on both the onset of acute gastric mucosal injury and its progression to ulcer lesion induced by ischaemia-reperfusion. Both effects of plaunotol on increase in prostaglandin content in gastric tissues and inhibition of superoxide radical from leucocytes may play important roles on the protection against gastric mucosal injury.

Cisplatin decreases renal cyclooxygenase-2 expression and activity in rats

Cisplatin (CP) induced acute renal failure (ARF) has previously been associated with decreased urinary prostaglandin E2 (PGE2) excretion and reduced aquaporin 2 (AQP2) expression in kidney collecting duct. In this study we examined the expression of cyclooxygenase (COX)-1 and -2 as well as AQP2 and the Na-K-2Cl cotransporter in kidneys from rats with CP induced ARF. Rats were treated with either CP or saline and followed for 5 days. Kidneys were dissected into three zones and prepared for immunoblotting, quantitative polymerase chain reaction (QPCR) and immunohistochemistry. Renal content and urinary PGE2 excretion was measured. Cisplatin treatment was associated with polyuria and a significant decreased creatinine clearance. Inner medullary PGE2 content and urinary PGE2 excretion was decreased in CP-treated rats. QPCR and semiquatitative immunoblotting demonstrated that CP treatment reduced COX-2, AQP2 and Na-K-2Cl cotransporter abundance in the different kidney zones, whereas no change in COX-1 was observed. Results were confirmed by immunohistochemistry. Cyclooxygenase-2 expression is decreased in inner medulla and cortex. Consistent with this urinary PGE2 levels were reduced. These data suggest that downregulation of COX-2 is responsible for impaired de novo generation of vasodilatory prostaglandins which may play an important role for the CP induced renal vasoconstriction and development of nephropathy.

Adrenal gland responses to lipopolysaccharide after stress and ethanol administration in male rats

All forms of stress, including restraint stress (RS) and lipopolysaccharide (LPS) administration, activate the hypothalamic–pituitary–adrenal (HPA) axis. LPS binds to a recognition protein (CD14) and toll-like receptor 2/4 in different cells and tissues, including the adrenal gland, to induce the production of cytokines and cause upregulation of cyclooxygenase and nitric oxide synthase (NOS) enzymes. Acute ethanol exposure activates the HPA axis, but in some conditions prolonged administration can dampen this activation as well as decrease the inflammatory responses to LPS. Therefore, this study was designed to evaluate the adrenal response to a challenge dose of LPS (50 μg/kg) injected i.p., after submitting male rats to RS, twice a day (2 h each time) for 5 days and/or ethanol administration (3 g/kg) by gavage also for 5 days, twice daily. At the end of the experiment, plasma corticosterone concentrations and adrenal gland content of prostaglandin E (PGE) and NOS activity were measured as stress mediators. The results showed that repetitive ethanol administration attenuated the adrenal stress response to LPS challenge alone and after RS, by preventing the increase in plasma corticosterone concentrations and by decreasing the PGE content and NOS activity in the adrenal gland. Therefore, we conclude that moderate alcohol consumption could attenuate the effects of psychophysical stress and impair an inflammatory response.

Reduced methacholine-induced submandibular salivary secretion in rats with experimental periodontitis

ObjectiveSaliva is the first barrier to the entry of bacteria and viruses into the body and is considered a necessary instrument in oral health. Intraperitoneal injection of lipopolysaccharide endotoxins results in submandibular gland (SMG) hyposalivation. The objective of present studies was to assess if periodontitis, a chronic inflammatory disease caused by oral bacteria, alters cholinergic-induced SMG salivary secretion. DesignAn experimental periodontitis model (EP) (cotton thread ligature around the neck of the first lower molars) was used. Male Wistar rats (300–380g) were randomly divided into 3 groups: control, 7 days-bilateral EP and 7 days-unilateral EP (to study if there were different effects at the ipsilateral and contralateral side). The following determinations were performed in SMG: (1) dose–response curves to the cholinergic agonist methacholine, (2) prostaglandin E (PGE) content, (3) inducible nitric oxide synthase (iNOS) activity and (4) histology of gland sections. ResultsThe molars with EP, no matter the group, exhibited significant and similar bone loss (p<0.001). Bilateral EP reduced methacholine-induced salivary secretion (p<0.05, dose 1μg/kg; p<0.001, dose 3–30μg/kg), increased PGE content (p<0.01), stimulated iNOS activity (p<0.05). Ipsilateral glands of unilateral EP animals presented lower methacholine-induced salivary secretion (p<0.05, dose 3μg/kg; p<0.001, dose 10–30μg/kg), and higher PGE content than contralaterals (p<0.001). In turn, at 3 and 10μg/kg of methacholine, contralateral glands showed significantly lower secretion than control animals (p<0.001). Histological studies of glands revealed partial loss of secretor granular material and periductal oedema in the bilateral and unilateral EP groups as compared to controls. ConclusionsAs far as we know, the present results demonstrate for the first time that EP reduces methacholine-induced SMG salivary secretion.

The effect of hemostasia on peptic ulcer hemorrhage by endoscopic local injection treatment

Objective To investigate the effect of the treatment of hemorrhagic peptic ulcer under the endoscope. Methods 80 patients with peptic ulcer bleeding according to different treatment methods were divided into talo groups:42 cases in treatment group and 38 cases in control group. The clinical efficacy、tissue prostaglandin E2 (PGE2) levels、 length of stay and adverse reactions were observed. Results The curative effect of 39 cases (92. 8%)in treatment group were significantly higher than that of 27 cases (71.0%) in control group( x2 = 4. 123,P ＜ 0. 05) ;The contents of PGE2(2.60 ± 0.68mg)/g after treatment in treatment group were significantly higher than before treatment ( 1.49 ± 0.43 ) mg/g( t = 2.415, P ＜ 0. 05 ); The contents of PGE2 after treatment in treatment group were significantly higher than that of the control group after treatment ( 1. 44 ± 0.42) mg/g( t = 2. 345,P ＜ 0. 05 ); The average length of stay in control group was (6.3 ± 1.8) days, higher than that of the treatment group ( 9.7 ± 2.4) days (t= 2.413, P ＜ 0. 05 ). Conclusion The curative effect of hemostasia treatment under the endoscope was positive and decrease the surgical intervention rate. Key words: Peptic ulcer; Bleeding; Treatment under endoscope

Gastroprotective activity of a new semi-synthetic solidagenone derivative in mice

The gastroprotective activity of the new semi-synthetic solidagenone derivative 15,16-epoxy8(9),13(16),14-labdatrien-7 beta-methoxy-6 beta-ol (ELMO) has been assessed on the model of HCl/EtOH-induced gastric lesions in mice. Human gastric epithelial cells (AGS) and fibroblasts (MRC-5) were used to determine its mode of action. The effect of ELMO on the prostaglandin E2 content, cellular reduced glutathione (GSH) and protection against damage induced by sodium taurocholate was assessed against AGS cells. The effect of ELMO on the growth of AGS and fibroblast cultures was evaluated. The superoxide anion scavenging capacity of the compound was studied also. The cytotoxicity of ELMO, expressed as cell viability, was assessed using two independent endpoints: neutral red uptake (NRU) and the reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) for MRC-5 fibroblasts and NRU for AGS cells. A single oral dose of ELMO (10 and 20 mg kg(-1)) inhibited the appearance of gastric lesions in mice displaying similar values to lansoprazole at 20 mg kg(-1). At 40 microM ELMO increased the prostaglandin E2 content but not GSH in AGS cells. The compound showed no effect on sodium taurocholate-induced damage and was devoid of superoxide anion scavenging activity. Concentrations of 0.5, 1, 2 and 4 microM stimulated fibroblast but not AGS cell proliferation. The compound showed weak cytotoxicity with values (IC50) of 411 (NRU) and 418 microM (MTT) for fibroblasts and 261 microM (NRU) for AGS cells. The results support further pharmacological study of this compound as a potential new anti-ulcerogenic drug.