Inflammation in cerebral ischemia reperfusion improved by avanafil via nod-like receptor protein-3 inflammasome: an experimental study in rats.

OBJECTIVE: The aim of study was to investigate the effect of avanafil, a second-generation phosphodiesterase-5 (PDE5) inhibitor, on cerebral ischemia reperfusion (CI/R) model. METHODS: 32 male albino Wistar rats were used. Four groups were constituted, as I: the healthy (sham), II: the CI/R group, III: the CI/R +I 10 mg/kg avanafil group, and IV: the CI/R + 20 mg/kg avanafil group. Avanafil was administered twice via oral gavage, first shortly after ischemia reperfusion and once more after 12 h. The rats were euthanized after 24 h. Histopathological and Real Time PCR analyzes were performed on cerebral tissues. RESULTS: IL-1ß, NLRP3 and TNF-α mRNA expressions were statistically higher in the CI/R group when compared to healthy (sham) group. Conversely, the IL-1ß, NLRP3, and TNF-α mRNA expressions were significantly decreased in both of the avanafil-treated groups when compared to CI/R group. Histopathological results showed that both doses of avanafil also decreased cellular damage in cerebral tissue that occurred after CI/R. CONCLUSION: Avanafil, was found to have ameliorated inflammatory response and cellular injury caused by CI/R. The mRNA expression of IL-1ß, NLRP3, and TNF-α decreased in the I/R groups and approached the control group levels with a high dose of avanafil.

Targeting Aquaporin-5 by Phosphodiesterase 4 Inhibition Offers New Therapeutic Opportunities for Ovarian Ischemia Reperfusion Injury in Rats.

This study aimed to examine the effect of Phosphodiesterase 4 (PDE4) inhibition on Aquaporin-5 (AQP5) and its potential cell signaling pathway in the ovarian ischemia reperfusion (OIR) model. Thirty adult female rats were divided into five groups: Group 1; Control: Sham operation, Group 2; OIR that 3 hour ischemia followed by 3 hour reperfusion, Group 3; OIR + Rolipram 1 mg/kg, Group 4; OIR + Rolipram 3 mg/kg, Group 5; OIR + Rolipram 5 mg/kg. Rolipram was administered intraperitoneally to the rats in groups 3-4 and 5 at determined doses 30 minutes before reperfusion. From ovary tissue; Tumor necrosis factor-a (TNF-α), Cyclic adenosine monophosphate (cAMP), Nuclear factor kappa (NF-κB), Interleukin-6 (IL-6), Phosphodiesterase 4D (PDE4D), Mitogen-activated protein kinase (MAPK) and AQP5 levels were measured by ELISA. We also measured the level of AQP5 in ovary tissue by real-time reverse-transcription polymerase chain reaction (RT-PCR). In the OIR groups; TNF-α, NF-κB, IL-6, MAPK inflammatory levels increased, and cAMP and AQP5 levels decreased, which improved with the administration of rolipram doses. Also histopathological results showed damaged ovarian tissue after OIR, while rolipram administration decrased tissue damage in a dose dependent manner. We propose that the protective effect of PDE4 inhibition in OIR may be regulated by AQP5 and its potential cell signaling pathway and may be a new target in OIR therapy. However, clinical studies are needed to appraise these data in humans.

Effect of trimetazidine against ovarian ischemia/reperfusion injury in rat model: A new pathway: JAK2/STAT3.

Objectives: Ovarian ischemia/reperfusion (I/R) is an extremely complex pathological problem that begins with oxygen deprivation, progresses to excessive free radical production, and intensifies inflammation. The JAK2/STAT3 signaling pathway is a multipurpose signaling transcript channel that plays a role in several biological functions. Trimetazidine (TMZ) is a cellular anti-ischemic agent. This study aims to investigate the effects of TMZ on ovarian I/R injury in rats. Materials and Methods: sixty four rats were divided into 8 groups at random: healthy(group1); healthy+TMZ20(group2); ischemia (I) (group 3); I+TMZ10(group4); I+ TMZ20(group5); I/R(group6); I/R+TMZ10(group7); I/R+TMZ20(group8). Vascular clamps were placed just beneath the ovaries and over the uterine horns for 3 hr to induce ischemia. The clamps were removed for the reperfusion groups, and the rats were reperfused with care to ensure that the blood flowed into the ovaries, subjecting them to reperfusion for 3 hr. TMZ was administered orally by gavage 6 and 1 hr before operations. At the end of the experiment, ovarian tissues were removed for biochemical, molecular, and histopathological investigation. Results: TMZ administration ameliorated ischemia/reperfusion-induced disturbances in GSH and MDA levels. TMZ treatment inhibited I/R-induced JAK2/STAT3 signaling pathway activation in ovarian tissues. TMZ administration also improved the increase in the mRNA expressions of IL-1ß, TNF-α, and NF-κB caused by ischemia/reperfusion injury. Moreover, TMZ treatment improved histopathologic injury in ovarian tissues caused by ischemia/reperfusion. Conclusion: TMZ treatment protected rats against ovarian ischemia/reperfusion injury by alleviating oxidative stress and inflammatory cascades. These findings may provide a mechanistic basis for using TMZ to treat ovarian ischemia-reperfusion injury.

Investigation of the effects of astaxanthin in experimental polycystic ovary syndrome (PCOS) in rats.

Objectives: The aim of this study was to investigate the effect of Astaxanthin (ASX) on ovaries in letrozole-induced polycystic ovary syndrome (PCOS) model in female rats by histopathological, immunohistochemical and biochemical techniques. Materials and Methods: Seventy two Sprague-Dawley female rats with an average weight of 200-250 gr and 10-12 weeks old were randomly divided into 9 groups. PCOS model was applied to all groups except healthy group. In the study, low (10 mg / kg) moderate (20 mg / kg) and high (40 mg / kg) doses of ASX were given to the experimental animals in the PCOS-induced groups for 7 days. At the end of the experiment, ovarian tissues were evaluated histopathologically, immunohistochemically, and biochemically. Results: When the histopathological findings were examined, many cystic follicles, apoptotic and necrotic cells were found in the follicles in the PCOS group. In addition, significant decrease in apoptotic and necrotic cells were observed in PCOS+MET+ASX and PCOS+ASX groups. In immunohistochemical staining findings, while TNF-α NF-κB and IL-6 expression levels showed significant increase in PCOS group, these expression levels were decreased in PCOS+MET+ASX and PCOS+ASX groups. In the biochemical evaluations, while MDA were increased, SOD were decreased in the PCOS group. MDA level were decreased while SOD levels were increased in the PCOS+MET+ASX and PCOS+ASX groups. Conclusion: In addition to the formation of insulin resistance in the tissue, severe oxidative stress damage occurs in ovarian tissue during PCOS. Metformin improved PCOS by correcting insulin resistance. In this period, the administration of ASX with Metformin protected the ovary from oxidative stress damage.

The effects of tarantula cubensis extract on renal ischemia reperfusion injury in rats.

BACKGROUND: Renal ischemia-reperfusion (IR) related acute kidney injury (AKI) is an important health problem and has not yet been fully treated. Tarantula cubensis extract (TCE) is a homeopathic drug that has antiinflammatory and antioxidant effects. This study aimed to investigate the effects of TCE on renal ischemia-reperfusion injury in rats. METHODS: This study was carried out on 48 Spraque-Dawley male rats, which were divided into six groups. The first, second, and third groups were control, sham, and IR groups, respectively. Group four received IR and 0.2 mL of 96% ethanol. Group five and six received ischemia and reperfusion and TCE 0.01 and 0.1 mg per rat (which correspond to approximately 0.04 mg/kg, and 0.4 mg/kg), respectively. Tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1ß), total antioxidant status (TAS), and total oxidant status (TOS) levels in renal tissue were measured by enzyme-linked immunosorbent assay (ELISA). Oxidative stress index (OSI) was obtained by proportioning TAS and TOS. Superoxide dismutase (SOD), myeloperoxidase (MPO) activities, and malondialdehyde (MDA) levels were determined by manual spectrophotometric methods. The histopathological changes were evaluated via hematoxylineosin and immunohistochemical staining. RESULTS: In IR group, renal tissue TNF-α and IL-1ß levels were significantly higher than control group (p < 0.0001 for both), and low(p < 0.0001 for both) and high dose (p < 0.0001 for both) TCE administration decreased these markers. Low and high doses of TCE decreased OSI values compared with IR group (p = 0.04 and p = 0.001 respectively). Although TCE decreased MDA levels, it was not statistically significant. MPO levels significantly decreased. In addition, TCE has been found to prevent hemorrhage, cast formation, and dilatation caused by IR in renal tissues stained with hematoxylin-eosin. And also, the most intense nuclear factor kappa B (NFκB) and caspase-3 immunopositivity found in IR group was decreased in both of the TCE groups. DISCUSSION: Although TCE showed a protective effect by inhibiting inflammation against IR damage in renal tissues, there was no clear effect on oxidative stress. Larger and more detailed studies are needed to clarify the issue.

Protective effects of a natural product, paeoniflorin, on ischemia reperfusion injury on rat ovary tissue: histopathological, immunohistochemical, and biochemical study.

In this study, the main hypothesis is that paeoniflorin may inhibit some cellular processes such as oxidative stress and inflammation. For this reason, we aimed to investigate the potential protective effects of a natural compound, paeoniflorin, on rat model of ovarian ischemia-reperfusion injury by detecting the oxidative stress parameters and inflammatory process parameters. 42 female Wistar-albino rats were divided into 6 random groups. The rats were subjected to 3-hour ischemia and 3-hour reperfusion process. Then, paeoniflorin at doses of 25, 50 and 100 mg/kg were applied 30 min before the reperfusion. The levels of pro-inflammatory (IL-1-ß, IL-6, TNF-α) and anti-inflammatory (IL-10, TGF-ß) cytokines were measured by ELISA. Similarly, IL-6, IL-10, TNF-α, NF-κB p65) positivity rates were detected by immunohistochemical staining. Additionally, oxidative stress parameters (MDA, GSH, SOD) were measured by tissue biochemistry. Ischemia-reperfusion injury caused significant increase in the levels of SOD, MDA, TNF-α, IL-1-ß, IL-6 and NF-κB p65, while paeoniflorin treatments improved the related parameters in a dose-dependent manner. As a conclusion, our findings support the evidence that paeoniflorin has a potential protective effects on ovarian ischemia-reperfusion injury. Further detailed studies should be performed to shed light the molecular mechanism of these protective effects.

Effects of Polygonum cognatum Meissn. extract on indomethacin induced gastric damage in rats.

We investigated the anti-ulcer activity of ethanol extracts of Polygonum cognatum on indomethacin induced gastric damage in rats. We evaluated the number of ulcer areas, oxidant and antioxidant parameters as well as histopathologic features in rat stomach. We measured the total antioxidant status of P. cognatum in concentrations from 1.56-100 mg/ml. P. cognatum extract inhibited indomethacin induced ulcer formation with an effect similar to a 20 mg/kg dose of the standard anti-ulcer drug, esomeprazole. All doses of P. cognatum extract exhibited positive effects on oxidative stress markers and histopathological features in the stomach tissue of rats. We suggest that the antioxidant activity of P. cognatum extract may be responsible for its gastroprotective effect and that P. cognatum extract may be a useful gastroprotective agent.

Antipsychotics Induced Reproductive Toxicity by Stimulating Oxidative Stress: A Comparative in Vivo and in Silico Study.

The pathophysiological mechanism behind the link between antipsychotic drugs and sexual dysfunction is still unknown. The goal of this research is to compare the potential effects of antipsychotics on the male reproductive system. Fifty rats were randomly assigned into the five groups indicated: Control, Haloperidol, Risperidone, Quetiapine and Aripiprazole. Sperm parameters were significantly impaired in all antipsychotics-treated groups. Haloperidol and Risperidone significantly decreased the level of testosterone. All antipsychotics had significantly reduced inhibin B level. A significant reduction was observed in SOD activity in all antipsychotics-treated groups. While GSH levels diminished, MDA levels were rising in the Haloperidol and Risperidone groups. Also, the GSH level was significantly elevated in the Quetiapine and Aripiprazole groups. By causing oxidative stress and altering hormone levels, Haloperidol and Risperidone are damaging to male reproductivity. This study represents useful starting point for exploring further aspects of the underlying mechanisms reproductive toxicity of antipsychotics.

Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol­induced acute liver injury.

The renin-angiotensin-aldosterone system (RAAS) is an important pathway that contributes to the pathophysiology of acute liver injury due to paracetamol toxicity. Omapatrilat, a RAAS-acting agent, inhibits both angiotensin converting enzyme (ACE) and neprilysin/neutral endopeptidase (NEP). The aim of the present study was to investigate the hepatoprotective effects of omapatrilat and examine the role of ACE/NEP pathway on the physiopathology of paracetamol toxicity. A total of 56 BALB/c mice were separated into seven groups: Control, 40 mg/kg omapatrilat only, 400 mg/kg paracetamol only, paracetamol and 140 mg/kg N-acetylcysteine and three groups with paracetamol and 10-40 mg/kg omapatrilat. Blood and liver tissue samples were studied through histopathological imaging, alanine transaminase (ALT) and aspartate transaminase (AST) liver function tests and oxidant/antioxidant biomarker measurements including superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA). ACE and NEP activities were also measured. Histopathological analysis revealed that paracetamol toxicity resulted in a number of apoptotic and necrotic cells in liver tissue samples. By contrast, with 40 mg/kg omapatrilat administration in toxicity-induced mice, hepatocytes were significantly improved and exhibited similar appearance to the control group. Biochemical measurements also supported these histopathological results. Omapatrilat pretreatment provided a dose-dependent reduction in oxidative stress and reversed paracetamol toxicity indications by reducing ALT and AST activities, increasing SOD activity and GSH levels and reducing MDA levels. Dose-dependent increase of ACE and NEP enzymes in omapatrilat groups was also observed. The results demonstrated promotion of antioxidant activity by omapatrilat and suppression of oxidative stress associated with acute liver injury. These findings revealed the potential role of ACE/NEP pathway in paracetamol toxicity and hepatoprotective effects of omapatrilat against oxidative stress.

Potential protective effect of astaxanthin on ovary ischemia-reperfusion injury.

Objectives: We thought that astaxanthin (ASX) might be a protective agent in oxidative stress damage that develops against ischemia and reperfusion injury in the rat ovary. Materials and Methods: The experimental groups consisted of healthy, I (Ischemia), I+ASX50, I+ASX100, I/R (Ischemia/Reperfusion), I/R+ ASX50, and I/R+ ASX100. Vascular clamps were applied to the ovaries for 3 hr to induce ischemia. For the reperfusion groups, the clamps were opened and blood flow was restored to the ovaries for 3 hr. At the end of the experiment, biochemical, histopathological, and immunohistochemical analyses were made from the tissue samples taken. Results: While MDA levels increased significantly in I and I/R groups, SOD levels decreased. It was found that ASX significantly decreased MDA levels and increased SOD activity in treatment groups depending on the dose. Caspase 3, IL-1 ß, and IL-6 expressions were severely increased in ischemia and I/R groups, while the severity of I+ASX50 and I/R+ASX100 immunoreactivity was decreased. While severe hemorrhage areas were observed in I and IR groups, minimal hemorrhage areas were observed in the treatment groups, especially in I/R+ASX100 groups. In addition, inflammatory cells and necrotic cells in the I/R group were not observed in I/R+ASX50 and I/R+ASX100 groups. Conclusion: As a result, it was determined that ASX has a strong protective role against oxidative damage in the treatment of ovarian ischemia-reperfusion injury.

The effects of dragon fruit (Hylocereus polyrhizus) extract on indomethacin-induced stomach ulcer in rats.

The aim of this study was to investigate the effects of red dragon fruit (Hylocereus polyrhizus) extract (DFE) on the stomach in ulcer model induced by indomethacin in rats. Effects of DFE were evaluated in indomethacin-induced gastric damage model on Sprague-Dawley rats. Experimental model: all rats were fasted for 24 h. At the end of this period, DFE was administered to the ulcer-induced groups. One hour after this application, a dose of 25 mg/kg of indomethacin was applied by oral gavage to all groups except the HEALTHY and DFE1000 groups. Six hours after indomethacin administration, the rats were euthanized with high-dose anesthesia and the experiment was terminated. Macroscopic and microscopic analyses for investigating ulcerative area, molecular and biochemical analyses for oxidative damages investigation and molecular analyses for the effect mechanism of indomethacin and DFE were conducted on stomach tissues in the study. While oxidative stress-associated markers such as MDA, BAX, and Caspase 3 increased dramatically in the indomethacin group, GSH antioxidant levels decreased. It was observed that these parameters were significantly improved in DFE 500 mg/kg and DFE 1000 mg/kg groups compared to ulcer group, and the results of especially DFE 1000 mg/kg group were similar to famotidine group. We observed that our histopathological findings also supported all our other findings. Dragon fruit extract was protected against indomethacin-induced ulcer damage by decreased MDA levels, increased GSH levels, and inhibition of Caspase 3, BAX, and Cox-2, and activation of Cox-1. PRACTICAL APPLICATIONS: People of all ages around the world suffer from gastric ulcer which is one of the most common gastrointestinal ailments. The etiological factors of the disease are using of cigarette and alcohol, nutritional deficiencies, infections, and using non-steroidal anti-inflammatory drugs which use frequent and indiscriminate. Indomethacin is one of the NSAIDs and is commonly preferred to induce ulcer modeling in rats due to its gastric toxicity potential. Current anti-ulcer drugs have many serious side effects. Patients who suffered from gastric ulcer tend to discontinue the drug because of side effects. Therefore, patients need new agents that are non-toxic, have few side effects, and are easily accessible anti-ulcer drugs. Dragon fruit, as a medicinal herb, is highly valuable and widely used in traditional medicine, and may provide gastroprotective activity. Studies have shown that H. polyrhizus has antioxidant activities. We consider the effects of dragon fruit extract (DFE) to be a therapeutic drug for an indomethacin-induced ulcer model.

Roflumilast as a Potential Therapeutic Agent for Cecal Ligation and Puncture-Induced Septic Lung Injury.

PURPOSE/AIMS: This study focused on delineating the possible effects of roflumilast (ROF), a selective phosphodiesterase 4 (PDE4) inhibitor, in rats with cecal ligation and puncture (CLP)-induced polymicrobial sepsis, and investigated whether ROF can act as a protective agent in sepsis-induced lung damage. MATERIAL AND METHODS: Four experimental groups were organized, each comprising eight rats: Control, Sepsis, Sepsis + ROF 0.5 mgkg-1, and Sepsis + ROF 1 mgkg-1 groups. A polymicrobial sepsis model was induced in the rats by cecal ligation and puncture under anesthesia. Twelve hours after sepsis induction, the lungs were obtained for biochemical, molecular, and histopathological analyses. RESULTS: In the sepsis group's lungs, the TNF-α, IL-1ß, and IL-6 mRNA expression levels peaked in the sepsis group's lung tissues, and ROF significantly decreased these levels compared with the sepsis group dose-dependently. ROF also significantly decreased MDA levels in septic lungs and increased antioxidant parameters (SOD and GSH) compared with the sepsis group. Histopathological analysis results supported biochemical and molecular results. CONCLUSIONS: ROF, a PDE4 inhibitor, suppressed the expression levels of pro-inflammatory cytokines, alleviated lung damage (probably by blocking neutrophil infiltration), and increased the capacity of the antioxidant system.

In Vivo and In Vitro Cardioprotective Effect of Gossypin Against Isoproterenol-Induced Myocardial Infarction Injury.

The aim of the study was to examine the protective effects and possible mechanism of gossypin against isoproterenol (ISO)-mediated myocardial damage in vivo and H9c2 cell damage in vitro. H9c2 cells were categorized into five groups. Viability was evaluated with MTT and LDH release in H9c2 cells. Apoptotic parameter analysis was performed with cytochrome c (Cyt-c), caspase-3 (CASP-3), and BCL2/Bax mRNA expression levels. In vivo, gossypin was administered orally to mice at doses of 5, 10, and 20 mg/kg for 7 days. ISO groups were injected with isoproterenol (150 mg/kg) subcutaneously (on 8th and 9th) for 2 days. Afterward, lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) levels and Troponin-I (Tn-I) amount from their serum, oxidative stress parameters superoxide dismutase (SOD) activity, glutathione (GSH) and malondialdehyde (MDA) levels, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1 ß), and NF-kB mRNA expression levels with inflammatory markers from heart tissue were evaluated. In addition, IL-1B, BCL-2, and cas-3 immunohistochemical staining was performed from heart tissue and TNF-a level was measured by ELISA method. Administration of Gossypin protected the cells by dose-dependent, eliminating the reduced cell viability and increased LDH release of ISO in H9c2 cells. In mice serum analyses, increased LDH, CK-MB levels, and Tn-I levels were normalized by gossypin. ISO administration in heart tissue is regulated by gossypin with increased SOD activity, GSH amount, TNF-α, IL-6, IL-1ß, and NF-kB mRNA expression levels and decreased MDA amount. Overall, the present results demonstrated that gossypin has a potential cardioprotective treatment for ischemic heart disease on in vivo and in vitro.

Evaluation of the protective effects of gossypin for ischemia/reperfusion injury in ovary tissue.

AIM: Ovarian ischemia-reperfusion (I/R) injury is a serious gynecological condition that affects women of reproductive age and reduces ovarian reserve. Management of I/R injury with detorsion causes reperfusion damage, in which oxidative stress plays a central role. This study aimed to investigate whether the gossypin (GOS) with antioxidant properties, a flavonoid, has beneficial effects on the biochemical, molecular, and histopathological aspects of ovarian I/R injury. METHODS: Thirty-three female Balb/c mice were randomly divided into five groups as follows: Healthy (Sham-operated control group), I/R (IR group), I/R + GOS 5 (I/R with GOS 5 mg/kg), I/R + GOS 10 (I/R with GOS 10 mg/kg), and I/R + GOS 20 (I/R with GOS 20 mg/kg). This was followed by 3 h of ischemia and subsequent reperfusion for 3 h after detorsion was exposed. GOS was injected 2 h before reperfusion. RESULTS: IL-1ß, IL-6, TNF-α, NF-κB, and CASP-3 mRNA expressions, SOD (superoxide dismutase) activity, GSH (glutathione), and MDA (malondialdehyde) levels, and histopathological changes were evaluated in ovarian tissue. Histological examination indicated that treatment of ovarian I/R injury with GOS led to the improvement of ovarian tissue, which was accompanied by an increase in SOD activity and GSH level and a decrease in MDA level, NF-κB, TNF-α, IL-1ß, and IL-6 expressions. GOS was also corrected by reducing the elevated expression of CASP-3 as apoptosis-change marker. CONCLUSION: These findings indicate that the treatment of GOS may be useful as a conservative approach to reverse I/R injury via amelioration of oxidative stress parameters and histopathological scores, attenuation of inflammation, and the suppression of apoptosis.

Histopathological Overview of Experimental Ulcer Models.

Histopathology is the process of examining tissue that includes all the changes, when a diseased tissue shows compared to a healthy group with a result of a histological observation. Histopathology has become an essential process in medical experimental research and medical experimental models. Scientists have developed medical experimental animal models for these reasons and have pioneered new drug research for many years. One of these experimental researches is experimental ulcer models. This model, which was initially a single method, has led to the emergence of new models with the discovery of physiological processes on ulcers by scientists. Nowadays, researchers have performed many new peptic ulcer models on experimental animals over the years. The main point in the creation of the ulcer model is the increase in the stomach acid level and the removal or corruption of the gastric mucus. When the experimental models were examined histopathologically, it was seen that the most severe models were those induced by pyloric ligation, acetic acid application, and indomethacin. In these models, ulcer foci that progressed to the submucosa were common, while the superficial damage spreading to the entire surface was striking in the ethanol model. While epithelial losses are shown on the surface of the mucosa, foci of necrotic apoptotic cell clusters extending to the submucosa are shown according to the weight of the model. In addition, evidence of inflammation has been shared in almost all studies. All these results show that ulcer models can be created by many different mechanisms. However, similar findings were observed in almost all experiments. Whether the experimental model caused severe or mild ulceration changed the histological findings.

Isolation of Major Compounds and Gastroprotective Activity of Alchemilla Caucasica on Indomethacin Induced Gastric Ulcers in Rats.

OBJECTIVE: The Alchemilla genus, which belongs to the Rosaceae family, is known as Lady's mantle and is commonly used in traditional medicine. This study was designed to investigate the major metabolites isolation and gastroprotective effects of Alchemilla caucasica. MATERIALS AND METHODS: Phytochemical studies were carried out using column chromatography on Alchemilla caucasica. The gastroprotective effect of ethanol extract of this plant was tested on indomethacin-induced gastric ulcer model in rats. In addition, superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) parameters in the stomach tissue were examined. RESULTS: Quercetin-3-O-glucuronide, apigenin, and catechin were isolated from aerial parts of Alchemilla caucasica. When macroscopic ulcer index and histopathological results were analyzed, the extract at 200 mg/kg dose was found to be most effective. All doses of extract reduced MDA level and enhanced SOD activity and GSH level. CONCLUSION: The results of this study showed that Alchemilla caucasica has significant antiulcer activity. This effect was thought to be caused by antioxidant properties of flavonoids.

Do peripheral melatonin agonists improve bone fracture healing? The effects of agomelatine and ramelteon on experimental bone fracture.

Melatonin improves fracture healing, but the long-term use of melatonin seems impracticable in the treatment of fracture due to side effects caused by hormonal stress on chronological rhythm. Ramelteon (RAMEL) and agomelatine (AGO) are non-selective peripheral melatonin receptor (MT) agonists. This study investigated the effects on bone fracture healing of these MT agonists, which do not affect the central nervous system. The rats were divided into 6 groups, including Group 1 (SHAM): sham operated group; Group 2 (FRACTURE): femoral fracture control; Group 3 (FR + AGO30): femoral fracture + agomelatine 30 mg/kg; Group 4 (FR + AGO60): femoral fracture + agomelatine 60 mg/kg; Group 5 (FR + RAMEL3): femoral fracture + ramelteon 3 mg/kg; and Group 6 (FR + RAMEL6): femoral fracture + ramelteon 6 mg/kg. After 21 days, the rats were subjected to X-ray imaging. Bone healing was evaluated with hematoxylin-eosin (HE) staining. Messenger RNA (mRNA) expressions of bone formation markers, such as bone alkaline phosphatase (ALP), osteocalcin (OC), and osteopontin (OP), were evaluated by real-time polymerase chain reaction (RT-PCR) and with immunohistochemistry (IHC) staining. The radiographic fracture healing scores were statistically significantly higher in the FR + AGO60 group and the FR + RAMEL3 group than in the FRACTURE group. The histopathology and molecular results supported the radiographic results. It was shown that agomelatine and ramelteon increase bone fracture healing, leading to the conclusion that a preference for agomelatine, an antidepressant, and ramelteon, a sleep aid, will increase bone fracture healing in patients with fractures.

Is Ebselen A Therapeutic Target in Fracture Healing?

OBJECTIVE: We investigated the effect of ebselen on fracture healing in an experimental fracture model. MATERIALS AND METHODS: We divided rats into two groups, 6 rats in each: the experimental femur fracture control group and the ebselen treatment group with an experimental femur fracture. In the experimental femur fracture control group, we created only experimental femur fracture. In the ebselen treatment group, we administered ebselen treatment with creating an experimental femur fracture. We administered ebselen intraperitoneally at 5 mg/kg once daily for 1 month after the 1st day of experimental femur fracture in the ebselen treatment group. We evaluated the recovery status of fractured femurs at the end of 1st month with radiographic, histopathological, and immunohistochemical methods. RESULTS: According to the radiographic fracture healing scores, ebselen treatment increased the extent of new bone formation and fracture cartilage callus significantly compared to the control group. According to the histopathological recovery scores, ebselen treatment significantly improved healing scores compared to the control group. Ebselen treatment increased the expression scores of bone healing markers in the ebselen treatment group, such as vascular endothelial growth factor and osteocalcin, compared to the control group. CONCLUSION: We demonstrated that ebselen treatment increases the formation of new bone in the femur in an experimentally created femoral fracture model. Ebselen has been shown to improve the bone fracture healing in a radiological and histopathological manner, and more detailed studies are needed.

Effects of soy isoflavonoids (genistein and daidzein) on endometrial receptivity.

OBJECTIVES: This study aimed to examine the effects of genistein and daidzein on endometrial receptivity by histopathological, immunohistochemical, and biochemical techniques. MATERIALS AND METHODS: In this study, 72 female Sprague-Dawley rats were randomly divided into 8 groups. The endometrial receptivity model was applied to identified groups. Experimental animals were given periorally 10 mg/kg and high 40 mg/kg doses of genistein and daidzein for 5 days by gavage. At the end of the experiment, uterine tissues were evaluated histopathologically, immunohistochemically, and biochemically. RESULTS: When histopathological findings were examined, significant decreases in pinopod formation were observed in high dose genistein and daidzein groups. When compared with the endometrial receptivity group, immunohistochemical staining findings showed a significant decrease in the expression of integrin ß3, integrin αvß3, LIF, and HOXA10 and an increase in MUC 1 expression in the high dose of genistein and daidzein groups. In biochemical evaluations, it was determined that genistein and daidzein increased estrogen levels and decreased progesterone levels in a dose-dependent manner. CONCLUSION: Genistein and daidzein have a negative effect on endometrial receptivity. Therefore, individuals with a risk of infertility should pay attention to the consumption of genistein and daidzein.