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Aim: The renin-angiotensin-aldosterone system (RAAS) plays important roles in oxidative stress and various gastroenterological mechanisms. Omapatrilat, an RAAS-acting agent, inhibits both neprilysin neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE) and may therefore affect protective mechanisms against gastric ulcer. Therefore, this study examined the gastroprotective role of omapatrilat in a mouse model of gastric ulcer induced by indomethacin to reveal pharmacological and biochemical changes resulting from omapatrilat treatment. Materials and Methods: Forty-two BALB/c mice were divided into seven groups: control, 40 mg/kg omapatrilat only, 25 mg/kg indomethacin only, indomethacin and 40 mg/kg famotidine, and three groups with indomethacin and 10-40 mg/kg omapatrilat. All chemicals were administered by oral gavage in 0.5 mL of 0.9% NaCl solution at the determined doses. Stomach ulcers were induced by indomethacin in mice treated with famotidine (40 mg/kg) and omapatrilat (10-40 mg/kg). Stomach tissue samples were examined macroscopically. Oxidative stress biomarkers of malondialdehyde (MDA), glutathione (GSH), NEP and ACE levels as well as superoxide dismutase (SOD) activity were measured. Results: The best antiulcer activity was measured with 40 mg/kg omapatrilat, where the gastric damage observed in the ulcer groups was significantly reversed, and gave the most similar results to the specific famotidine treatment. In relation with the increasing omapatrilat dose, SOD activity was corrected as well as GSH and MDA levels. Also the levels of ACE and NEP decreased back towards those measured in the control group. Therefore, these macroscopic and biochemical findings indicating reversal of gastrotoxicity and gastric ulcer indications demonstrate the role of omapatrilat’s NEP and ACE inhibition in indomethacin toxicity, and its strong gastroprotective potential. Conclusion: Dual inhibition of NEP and ACE by omapatrilat may suppress oxidative stress associated with indomethacin-induced gastric ulcer. Therefore, the protective effect of omapatrilat in the treatment of ulcers may lead to the search for new treatment strategies.

Pomegranate peel contains bioactive ingredients such as flavonoids, ellagitannins, phenolics and proanthocyanidin compounds with high antioxidant activity. Pomegranate peel has antiapoptotic, antioxidant and anti-inflammatory effects due to its high punicalagin content. We aimed to determine the effect of pomegranate peel extract (PPE) on lipopolysaccharide (LPS)-induced uveitis. Sixty rats were seperated randomly into twelve groups (n = 5). The healthy group received intraperitoneal normal saline, the uveitis group received 200 μg/kg LPS, the dexamethasone (DEX) group received 200 μg/kg LPS plus 1 mg/kg DEX, the PPE100, PPE300 and PPE500 groups received 200 μg/kg LPS plus 100, 300 and 500 mg/kg PPE, respectively. The eye tissues were collected at 3rd and 24th hour. and investigated molecularly (Relative quantification of gene expression), biochemically (Superoxide dismutase activity, Glutathione and Malondialdehyde levels) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Tumor Necrosis Factor-α, vascular endothelial growth factor, and Caspase-3 levels markedly decreased in a dose-dependent manner in the uveitic rats following PPE administration. PPE administration significantly ameliorated uveitic disorders in oxidative stress factors including Glutathione, Superoxide dismutase and Malondialdehyde, with its effects raising in a dose-dependent manner. PPE eliminated histopathological changes in eye tissues due to uveitis. PPE can be a promising agent by contributing to alternative preventive treatment methods for uveitis with its anti-inflammatory, antioxidative, antiapoptotic and antiangiogenic effects.

Amaç: Bu çalışmanın amacı sıçanlarda letrozolle oluşturulmuş PKOS (polikistik over sendromu) üzerinde fisetinin antioksidan etkilerini değerlendirmektir. Gereç ve Yöntem: Çalışmada 36 adet Albino Wistar dişi sıçan kullanıldı. Dişi sıçanlara, PKOS modelini indüklemek için 21 gün boyunca %1 karboksimetil selüloz (2 mL/kg) içinde çözülmüş 1 mg/kg dozunda letrozol oral yolla uygulanmıştır. PKOS oluşturulduktan sonra 7 gün boyunca metformin ve fisetin kendi gruplarına uygulandı. Hayvanların overleri alındı ve biyokimyasal, histolojik incelemeler için uygun koşullarda saklandı. Bulgular: PKOS grubunda sağlıklı gruba göre glutatyon (GSH) seviyelerinde düşüş, malondialdehit (MDA) seviyelerinde artış görüldü. PKOS+MET+FIS25 (PKOS+20 mg/kg metformin+25 mg/kg fisetin) ve PKOS+MET+FIS50 (PKOS+20 mg/kg metformin+50 mg/kg fisetin) gruplarında doza bağlı olarak GSH seviyelerinin yükseldiği, MDA seviyelerinin düştüğü tespit edildi. Histolojik bulgularda PKOS grubunda kontrol grubuna göre çok sayıda kistik folikül içerdiği görüldü. PKOS+MET+FIS25 ve PKOS+MET+FIS50 gruplarında doza bağlı olarak kistik foliküllerin ve foliküllerin içerdiği apoptotik ve nekrotik hücrelerin azaldığı görüldü. Sonuç: Sonuç olarak, fisetin metforminin ortadan kaldıramadığı oksidatif hasarı engelleyerek faydalı etkiler göstermiştir. Fisetin antioksidan aktivite göstererek yeni hücrelerin nekroza gitmesini engellemiş ve korumuştur. Bundan dolayı metformin tedavisine fisetin eklenmesi faydalı olacaktır.

Objective(s): In this study, the effects of astaxanthin on liver tissue in rats with polycystic ovary syndrome (PCOS) were evaluated.Materials and Methods: Fifty-four Spraque-Dawley rats were divided into 9 groups: Groups: Control, PCOS, PCOS+Metformin (Met), PCOS+ Astaxanthin (ASX)10, PCOS+ASX20, PCOS+ASX40, PCOS+Met+ASX10, PCOS+Met+ASX20, and PCOS+Met+ASX40. PCOS was induced in female rats by oral administration of letrozole (1 mg/kg) for 21 days. Rats were treated with ASX (10 mg/kg), ASX (20 mg/kg), ASX (40 mg/kg), and metformin (20 mg/kg) for 7 days after PCOS induction. At the end of the experiment, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured in the liver tissue. The liver was stained with hematoxylin/eosin for histological examination. Additionally, NF-kB and caspase 3 were analyzed immunohistochemically.Results: A remarkable abnormality was observed in the biochemical and histological parameters in the liver tissue of the PCOS model rats. Astaxanthin dose-dependently normalized the MDA level. Additionally, astaxanthin showed a protective effect by increasing the SOD level and increasing its antioxidant activities. We observed that administration of astaxanthin in addition to metformin applied in the standard was more effective. Caspase 3 and NF-kB immune positivity was lower in the groups given astaxanthin compared with PCOS. Histologically, it was observed that astaxanthin improved the deteriorated liver morphology in the letrozole-induced PCOS group.Conclusion: According to our results, it was observed that astaxanthin had antioxidant, anti-inflammatory and anti-apoptotic effects on PCOS in the treatment groups. Therefore, it was concluded that astaxanthin may have a protective effect against PCOS side effects.

Purpose: In this study, our aim was to investigate the potential effects of strong antioxidant daidzein (DZ) on ovarian ischemia and reperfusion injury. Materials and Methods: A total of 42 female Sprague-Dawley rats were randomly divided into seven groups. For the experimental model, the clamps were removed after 3 hours of ischemia, and blood flow was provided again. Then, reperfusion process was terminated for 3 hours. Daidzein was orally administered to animals at doses of 35 and 70 mg/kg 30 minutes before ischemia (I) and ischemia and reperfusion (I/R) procedures. Results: Severe immunoreactivity of the IL-1β, IL-6 and Caspase-3 were detected in I and I/R groups. Moderate immunoreactivity of IL-1β, IL-6 and Caspase-3 was detected in I+DZ35 and I/R+DZ35 groups, and slightly positivity was detected in I+DZ70 and I/R+DZ70 groups. The SOD activity level increased in the groups treated with Daidzein, while MDA levels decreased. In addition, hemorrhage areas and inflammatory cell migration decreased in I/R+DZ70 and I/R+DZ35 groups, when compared to I/R group in a dose dependent manner. Conclusion: Daidzein has a strong protective role in the treatment of ovarian ischemia-reperfusion injury and can be used as a therapeutic agent.

Objective(s): 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 β3, integrin αvβ3, 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.

Purpose: We aimed to examine the potential protective effects of phloretin and phloridzin in indomethacin induced ulcer model in mice. Materials and Methods: In total 54 female Balb/C mice were separated into nine groups. Famotidine was used as standard antiulcer agent. The phloretin and phloridzin was given at the doses of 50 and 100 mg/kg as a pre-treatment. After experimental procedures stomach tissue oxidative parameters (SOD, GSH and MDA), inflammatory cytokine TNF-α, and COX1 and COX2 mRNA expressions were analyzed. In addition, to clarify antiulcer effect mechanism of phloretin and phloridzin, numerical densities of ulcerative areas were analyzed. Results: Phloretin and phloridzin inhibited indomethacin-induced ulcer formation in dose dependent manner. Tissue inflammation and oxidative stress were increased after the indomethacin administration. Phloretin and phloridzin treatment normalized all parameters compared to indomethacin treated group. After the treatments, SOD activities and GSH levels were increased while MDA levels were decreased. Phloretin and phloridzin treatments decreased TNF-α, COX1 and COX2 mRNA expressions. Conclusion: Our results showed that phloretin and phloridzin may be an alternative treatment for peptic ulcer disease due to their potential regulatory effects against oxidative stress and inflammation.