Moklobemidin Sıçanlarda Antiülser ve Antioksidan Aktivitesinin Araştırılması

Amaç: Peptik ülser tedavisinde kullanılan çok sayıda klasik antiülser ilaç grupları bulunsa da, bu ilaçlar ile ülserin kalıcı tedavisi sağlanamamaktadır. 1950'den beri antidepresan ilaçlar non - psikiyatrik bazı hastalıkların tedavisinde kullanılmaktadırlar. Birçok antidepresan ilacın antiülser aktiviteye sahip oldukları deneysel ve klinik çalışmalarla da gösterilmiştir. Moklobemid, monoaminooksidaz - A (MAO - A) enziminin selektif inhibitörü antidepresan bir ilaçtır. Klasik MAO inhibitörleri ile karşılaştırıldığında, etkinliğinin fazla olması ve yan etkilerinin az olması nedeni ile depresyon tedavisinde tercih edilmektedir. Bu çalışmada sıçan mide dokusunda moklobemidin antiülser etkilerinin araştırılması ve oksidan mekanizmalarla ilişkisinin belirlenmesi amaçlanmıştır. Gereç ve Yöntem: 10, 20, 40, 80 ve 150 mg/kg dozlarında kullanılan moklobemid ve 20 mg/kg dozunda kullanılan famotidinin antiülser aktivitesi sıçanlarda indometazin ile indüklenen ülser modelinde incelenmiş ve sonuçlar kontrol grubu ile karşılaştırılmıştır. Bulgular: Moklobemid kullanılan tüm dozlarda indometazin ülserlerinin oluşumunu anlamlı olarak azalttı. Moklobemid, kullanılan bu dozlarda sıçan mide dokusunda glutatyon (GSH), nitrik oksid (NO) seviyeleri ve süperoksid dismutaz (SOD) aktivitesini kontrol grubuna göre artırırken; malondialdehid (MDA) seviyesi ve myeloperoksidaz (MPO) aktivitesini ise azaltmıştır. Sonuç: Antidepresan bir ilaç olan moklobemidin, güçlü bir antiülser ajan olduğu tespit edilmiştir. Moklobemidin antiülser etki mekanizmasında toksik oksidan radikallerin baskılanması ve antioksidan mekanizmaların aktivasyonu rol oynamaktadır.Objective: Even though there are many drugs for the treatment of gastric ulcers, these drugs sometimes cannot succeed. Since the 1950s, antidepressant drugs have been used for several non-psychiatric indications. Many antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. Moclobemide is an antidepressant drug which inhibits monoamine oxidase-A (MAO) enzyme selectively. When it is compared to the classic antidepressants drugs, moclobemide is the first choice in depression treatment because of its effectiveness and less side effects. This study aimed to investigate the antiulcer effects of moclobemide and to determine its relationship with antioxidant mechanisms in rat gastric tissue. Materials and Methods: The antiulcer activities of 10, 20, 40, 80, 150 mg/kg moclobemide and 20 mg/kg famotidine have been investigated on indomethacin-induced ulcers in rats, and the results have been compared with that of the control group. Results: Moclobemide decreased the indomethacin-induced ulcers significantly at all doses used. While used doses of moclobemide increased the glutathione (GSH), nitric oxide (NO) level and superoxide dismutase (SOD) activity, it decreased the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in stomach tissue when compared to the control group.Conclusion: It is determined that an antidepressant drug, moclobemide is a potent anti-ulcer agent. Inhibition of toxic oxidant radicals and activation of antioxidant mechanisms play a role in its antiulcer effect mechanisms

Anti-inflammatory activity of 2,5-dihydroxycyclohepta-2,4,6-trienone in rats

In this study, the anti-inflammatory effects of a tropolone derivative, 2,5-dihydroxycyclohepta-2,4,6-trienone (AD-4), were investigated. The anti-inflammatory potency of AD-4 was compared with that of indomethacin in carrageenan-induced inflammation models in rats. The effect on vascular permeability was also determined by hyaluronidase-induced capillary permeability. AD-4 decreased carrageenan-induced paw edema at doses of 3.62 x 10(2), 7.24 x 10(2), and 14.48 x 10(2) mu mol/kg by 45% (p < 0.001), 79% (p < 0.001), and 83% (p < 0.001), respectively, compared with the value of 49% (p < 0.001) for indomethacin (69.8 mu mol/kg). Additionally, AD-4 decreased hyaluronidase-induced capillary permeability significantly. In conclusion, AD-4 was determined to have anti-inflammatory effects with lower toxicity than indomethacin. Anti-inflammatory effect of AD-4 may be related to its effects on vascular permeability

The effect of etoricoxib on kidney ischemia-reperfusion injury in rats: A biochemical and immunohistochemical assessment

Kurt, Nezahat/0000-0002-1685-5332; Albayrak, Abdulmecit/0000-0002-1062-1965; Gundogdu, Cemal/0000-0003-2857-923XWOS: 000347019800024PubMed: 25068826The purpose of this study was to investigate the effect of etoricoxib on oxidative injury induced with ischemia-reperfusion (I/R) in rat kidney tissue in terms of biochemistry and immunohistochemistry. Male Albino Wistar rats were divided into renal I/R (RIR), 50 mg/kg etoricoxib + RIR (ETO-50), 100 mg/kg etoricoxib + RIR (ETO-100) and sham operation (SG) groups. Animals in the ETO-50 and ETO-100 groups were given etoricoxib by the oral route at dosages of 50 and 100 mg/kg, respectively. the RIR and SG groups were given distilled water as solvent. One hour after drug administration, 1 h of ischemia and 3 h of reperfusion were applied to the left kidneys of all rats (apart from SG) under 25 mg/kg thiopental sodium anesthesia. At the end of that time, kidneys were extracted and biochemical and immunohistochemical analyses were performed. Etoricoxib reduced, in a dose-dependent manner, levels of MDA, MPO and COX-2 that normally rise with I/R in rat kidney tissues. Etorixicob did not alter COX-1 activity at 50 and 100 mg/kg doses, but significantly prevented loss of tGSH in tissues with I/R. in addition, Bd-2' gene expression inhibited with I/R was prevented in renal tubular and glomerular cells. Furthermore, etoricoxib significantly decreased the caspase-3 gene expression which increased with I/R. Etoricoxib significantly prevented I/R injury in a dose-dependent manner. the results of this study show that etoricoxib treatment could decrease kidney injury during IR. (C) 2014 Elsevier B.V. All rights reserved

The anti-inflammatory activity of 2,5-dihydroxycyclohepta-2,4,6-trienone in rats

In this study, the anti-inflammatory effects of a tropolone derivative, 2,5-dihydroxycyclohepta-2,4,6-trienone (AD-4), were investigated. The anti-inflammatory potency of AD-4 was compared with that of indomethacin in carrageenan-induced inflammation models in rats. The effect on vascular permeability was also determined by hyaluronidase-induced capillary permeability. AD-4 decreased carrageenan-induced paw edema at doses of 3.62 x 10(2), 7.24 x 10(2), and 14.48 x 10(2) mu mol/kg by 45% (p < 0.001), 79% (p < 0.001), and 83% (p < 0.001), respectively, compared with the value of 49% (p < 0.001) for indomethacin (69.8 mu mol/kg). Additionally, AD-4 decreased hyaluronidase-induced capillary permeability significantly. In conclusion, AD-4 was determined to have anti-inflammatory effects with lower toxicity than indomethacin. Anti-inflammatory effect of AD-4 may be related to its effects on vascular permeability

The Role of RAAS Inhibition by Aliskiren on Paracetamol-Induced Hepatotoxicity Model in Rats

Karakus, Emre/0000-0002-0822-0054; Albayrak, Abdulmecit/0000-0002-1062-1965; bayir, yasin/0000-0003-3562-6727; Mercantepe, Tolga/0000-0002-8506-1755WOS: 000368857900009PubMed: 26280784Paracetamol is one of the most popular and widely used analgesic and antipyretic agents, but an overdose can cause hepatotoxicity and lead to acute liver failure. Aliskiren directly inhibits renin which downregulates the renin-angiotensin-aldosterone system (RAAS). Recent findings suggest that RAAS system takes part in the pathogenesis of liver fibrosis. We aimed to reveal the relationship between hepatotoxicity and the RAAS by examining paracetamol induced hepatotoxicity. Rats were separated into five groups as follows: control, 100 mg/kg aliskiren (p.o.), 2 g/kg paracetamol (per os (p.o.)), 2 g/kg paracetamol + 50mg/kg aliskiren (p.o.), and 2 g/kg paracetamol + 100 mg/kg aliskiren(p.o.). Samples were analyzed at the biochemical, molecular, and histopathological levels. Paracetamol toxicity increased alanine aminotransferases (ALT), aspartate aminotransferases (AST), renin, and angiotensin II levels in the serum samples. in addition, the SOD activity and glutathione (GSH) levels decreased while Lipid Peroxidation (MDA) levels increased in the livers of the rats treated with paracetamol. Paracetamol toxicity caused a significant increase in TNF-alpha and TGF-beta. Both aliskiren doses showed an improvement in ALT, AST, oxidative parameters, angiotensin II, and inflammatory cytokines. Only renin levels increased in aliskiren treatment groups due to its pharmacological effect. A histopathological examination of the liver showed that aliskiren administration ameliorated the paracetamol-induced liver damage. in immunohistochemical staining, the expression of TNF-alpha in the cytoplasm of the hepatocytes was increased in the paracetamol group but not in other treatment groups when compared to the control group. in light of these observations, we suggest that the therapeutic administration of aliskiren prevented oxidative stress and cytokine changes and also protected liver tissues during paracetamol toxicity by inhibiting the RAAS. (C) 2015 Wiley Periodicals, Inc.Scientific Research Council of Ataturk UniversityAtaturk University [2012/352]Grant sponsor: Scientific Research Council of Ataturk University; Grant number: 2012/352

Comparative study on the gastroprotective potential of some antidepressants in indomethacin-induced ulcer in rats

Clinical studies have shown that anxiolytic and antidepressant drug therapy benefits patients with ulcers. Many antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. This study investigated the antiulcer activities of tianeptine, trazodone, and venlafaxine on indomethacin-induced ulcers in rats: and evaluated tianeptine's effects on oxidant and antioxidant parameters in rat stomach tissue. The results show that trazodone and venlafaxine did not prevent indomethacin-induced ulcers. Tianeptine, however, decreased indomethacin-induced ulcers significantly at all doses used (6,12, and 25 mg/kg). Famotidine, an H-2 receptor blocker, showed the highest antiulcer activity. Tianeptine significantly prevented the decrease in glutathione (GSH) content that occurred in the indomethacin-only group's damaged stomach tissues. All doses of tianeptine, but especially the 25 mg/kg dose, significantly decreased catalase (CAT) activity in stomach tissue, compared to the control. All doses of tianeptine eliminated the decrease in superoxide dismutase (SOD) activity in the stomach tissue of rats given indomethacin. Although all doses of tianeptine significantly decreased the malondialdehyde (MDA) content, all doses of tianeptine, except 6 mg/kg, decreased myeloperoxidase (MPO) activities significantly compared to the control. Our results indicate that activating enzymatic and non-enzymatic antioxidant mechanisms and inhibiting some toxic oxidant mechanisms play a role in tianeptine's antiulcer effect mechanism. (C) 2009 Elsevier Ireland Ltd. All rights reserved

Controlled reperfusion for different durations in the treatment of ischemia-reperfusion injury of the rat ovary: evaluation of biochemical features, molecular gene expression, and histopathology

High numbers of proinflammatory cells (PMNLs), which are carried by the blood to ischemic tissue during reperfusion, are considered responsible for inducing the inflammatory response that occurs in ischemia-reperfusion (I/R) injury. Our objective was to determine the controlled reperfusion (CR) interval duration (CRID) that would minimize the injury caused by the PMNLs that infiltrate ischemic tissue. Animal groups were divided into the following groups: Sham group, ovarian I/R group (OIR), and ovarian ischemia controlled-reperfusion groups OICR-1, OICR-2, OICR-3, OICR-4, OICR-5, OICR-6, which had their ovarian artery opened and then closed for 10, 8, 6, 4, 2, or 1 s, respectively. The results show that the COX-2 activity and the gene expression decreased while the COX-1 activity and the gene expression were found to be increased in parallel to the shortening of the period in CRID. From the histopathological examinations, the findings of hemorrhage, edema, congested vascular structures, degenerated cells, and migration and adhesion of PMNLs were scaled as follows: Sham group < OICR-6 < OICR-5 < OICR-4 < OICR-3 < OICR-2 < OICR-1. The results from the histopathological assessments were consistent with the molecular and biochemical findings. In conclusion, our findings suggest that increased COX-2 activity plays a role in I/R injury of the rat ovary, and that controlled reperfusion for 3, 2, or 1 s following 2 h of ischemia may attenuate the effects of I/R injury