Showing papers by "Meral Yüksel published in 2015"

Anti-inflammatory effects of nesfatin-1 in rats with acetic acid - induced colitis and underlying mechanisms.

Abstract: Mucosal balance impairment, bacterial over-proliferation, cytokines, inflammatory mediators are known as responsible for inflammatory bowel disease. Besides known anorexigenic, neuroprotective, and anti-apoptotic effects, the major effect of nesfatin-1 on colitis is unknown. Our aim was to investigate the possible anti-inflammatory effects of nesfatin-1 in acetic acid induced colitis model and potential underlying mechanisms. Male Spraque-Dawley rats were anesthetized by intraperitoneal ketamine (100 mg/kg) and chlorpromazine (0.75 mg/kg). For nesfatin-1 and antagonist applications some of the rats were intracerebroventricularly (i.c.v.) cannulated. In colitis group, intrarectally (i.r.) 4% acetic acid solution (1 ml) and 10 minutes later i.c.v. nesfatin-1 (0.05 μg/5 μl) or vehicle (5 μl) were administered. Treatments continued for 3 days. In control group, physiological saline solution was used intrarectally. To identify the underlying effective mechanism of nesfatin-1, rats were divided into 3 subgroups, 5 minutes following colitis induction; i.c.v. atosiban (oxytocin receptor antagonist), SHU9119 (melanocortin receptor antagonist) or GHSR-1a antagonist (ghrelin receptor antagonist) were administered, 5 minutes later nesfatin-1 was administered for 3 days. On the fourth day, rats were decapitated, and colon tissues were sampled. Macroscopic and microscopic damage scores of distal colon, and colonic tissue malondialdehyde, glutathione, myeloperoxidase, superoxide dismutase, catalase, luminol and lucigenin chemiluminescence measurements were analysed. The increased myeloperoxidase activity, malondialdehyde levels, luminol and lucigenin chemiluminescence measurements, macroscopic and microscopic damage scores with colitis induction (P < 0.05 - 0.001) were decreased with nesfatin-1 treatment (P < 0.05 - 0.001). Nesfatin-1 may show this effect by inhibiting neutrophil infiltration through tissues and by decreasing formation of free oxygen radicals. Atosiban and GHSR-1a administration alleviated the protective effect of nesfatin-1 from microscopic and oxidant damage parameters and lipid peroxidation (P < 0.05 - 0.001). The results of the study suggest that nesfatin-1 had a protective effect from colitis induction, and the anti-inflammatory and antioxidant effects of nesfatin-1 on colitis might occur via oxytocin and ghrelin receptors.

St. john's wort may ameliorate 2,4,6-trinitrobenzenesulfonic acid colitis of rats through the induction of pregnane x receptors and/or p-glycoproteins

Abstract: It is reported that deficiencies of the pregnane X receptor (PXR) and P-glycoprotein (P-gp), the latter of which is encoded by the MDR1 gene, are important factors in the pathogenesis of inflammatory bowel disease (IBD). It is also known that the activation of PXR is protective of IBD due to the mutual repression between PXR and nuclear factor kappa B (NF-κB) expression and because NF-κB was reported to play a pivotal role in the pathogenesis of ulcerative colitis. The goal of this study was to investigate whether St. John's wort (SJW) and spironolactone (SPL), both known to have strong inducing effects on cytochrome P 450 (CYP) enzymes as well as PXR and P-gp, have ameliorating effects on 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis of rats through induction of PXR and/or P-gp. Wistar albino rats (250 - 300 g) were divided into control and TNBS-colitis groups. Each group was then divided into a) control (saline), b) SJW (300 mg/kg p.o. bid), and c) SPL (80 mg/kg p.o.) groups. Drugs were given for 7 days. Both treatments ameliorated the clinical hallmarks of colitis, as determined by body weight loss and assessment of diarrhea, colon length, and bowel histology. Plasma levels of NF-κB, tumour necrosis factor-alpha (TNF-α) and tissue myeloperoxidase (MPO) activity, as well as the oxidative stress markers that increased during colitis, decreased significantly after both treatments. The PXR and P-gp expression in the intestinal tissues was diminished in the colitis group but increased after drug treatments. Both drugs appeared to have significant antioxidant and anti-inflammatory effects and ameliorated the TNBS colitis of the rats, most likely through their PXR- and P-gp-inducing properties.

Sıçanda endotoksemiye bağlı çoklu organ hasarında kolinerjik anti-inflamatuvar yolun rolü

Abstract: Amac: Sicanda sepsise bagli coklu organ hasarinda kolinerjik anti-inflamatuvar yolun rolunu arastirmak ve patojenezde induklenebilir nitrik oksit sentaz (iNOS) ve siklooksijenaz (COX)-2 enzimlerinin etkilesimini incelemektir. Yontemler: Sprague-Dawley sicanlara lipopolisakkarid (LPS) (10 mg/kg; intraperitoneal) uygulanarak sepsis olusturuldu. Tedavi gruplarina, LPS oncesi 3 gun sureyle nikotin (0.1 mg/kg; intraperitoneal) tek basina veya nikotinik reseptor antagonisti mekamilamin (3 mg/kg; subkutan), selektif iNOS inhibitoru aminoguanidin (8 mg/kg; intraperitoneal) veya selektif COX-2 inhibitoru nimesulid (8 mg/kg; intraperitoneal) ile birlikte uygulandi. LPS’den 6 saat sonra dekapite edilen sicanlarin karaciger, bobrek ve akciger orneklerinde malondialdehid (MDA), glutatyon (GSH), myeloperoksidaz (MPO) aktivitesi, kemiluminisans olcumleri ve hasar skorlamasi yapildi. Kanda alanin transaminaz (ALT), aspartat aminotransferaz (AST) ve ure azotu (BUN) olculdu. Bulgular: Sepsis kanda ALT (p<0.05), AST (p<0.01) ve BUN (p<0.001) duzeylerinde artisa, karaciger, bobrek ve akcigerde MDA’da yukselmeye (sirasi ile, p<0.01, p<0.05 ve p<0.05), MPO’da artisa (sirasi ile, p<0.01, p<0.05 ve p<0.001), GSH’da azalmaya (karaciger icin p<0.01, bobrek icin p<0.01) ve kemiluminisansta artisa (luminol her uc doku icin p<0.001; lusigenin karaciger icin p<0.001, bobrek ve akciger icin p<0.01) neden oldu. Nikotin ALT, AST ve BUN duzeylerindeki yukselmeyi (her uc parametre icin p<0.05), karaciger ve bobrekte MDA artisini (sirasi ile, p<0.05 ve p<0.05), GSH’daki azalmayi (sirasi ile, p<0.01 ve p<0.01), doku hasarini (sirasi ile, p<0.05 ve p<0.05) ve MPO artisini (karaciger icin p<0.05, bobrek icin p<0.01 ve akciger icin p<0.01) engelledi. Nikotinin yararli etkileri diger tedaviler varliginda devam etme egilimi gosterdi. Sonuc: Nikotin tedavisi sepsise bagli karaciger, bobrek ve akciger hasarini olasilikla iNOS ve COX-2 enzim sistemlerinden bagimsiz mekanizmalarla korumaktadir.