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Öğe Effects of quercetin on methotrexate-induced nephrotoxicity in rats(Sage Publications Ltd, 2017) Yuksel, Yasemin; Yuksel, Ramazan; Yagmurca, Murat; Haltas, Hacer; Erdamar, Husamettin; Toktas, Muhsin; Ozcan, OsmanObjective: This experimental study was conducted to elucidate the possible protective/therapeutic effects of quercetin against methotrexate (Mtx)-induced kidney toxicity with biochemical and histopathological studies. Methods: Twenty-four adult male rats were randomly divided into four groups, as follows: control group (saline intraperitoneally (i.p.), 9 days), Mtx group (20 mg/kg i.p., single dose), Mtx + quercetin group (50 mg/kg quercetin was orally administered 2 days before and 6 days after Mtx administration) and only quercetin group (50 mg/kg oral, 9 days). Structural changes were evaluated by hematoxylin-eosin and periodic acid-Schiff stainings. Apoptotic changes were investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and caspase-3 antibody. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured in tissue and plasma samples. Results: Mtx compared with the control group, there was significant increase in nephrotoxic tissue damage findings, in addition to apoptotic index (APOI) and caspase-3 expression (p < 0.05). Mtx + quercetin group revealed significantly lower histopathological damage and APOI and caspase-3 expression decreased when compared to Mtx group. MDA levels were increased in Mtx group compared to others, and by the use of quercetin, this increase was significantly reduced. SOD levels were higher in Mtx group than others. This increase was evaluated as a relative increase arising from oxidative damage caused by Mtx. Conclusion: As a result, Mtx administration may involve oxidative stress by causing structural and functional damage in kidney tissue in rats. Quercetin reduced the Mtx-induced oxidative stress through its antioxidant properties and so quercetin may be promising to alleviate Mtx-induced renal toxicity.Öğe Hypoxia causes important changes of extracellular matrix biomarkers and ADAMTS proteinases in the adriamycin-induced renal fibrosis model(Wiley, 2019) Armutcu, Ferah; Demircan, Kadir; Yildirim, Umran; Namuslu, Mehmet; Yagmurca, Murat; Celik, Hueseyin T.Aim Renal fibrosis is a common cause of renal dysfunction with chronic kidney diseases. This process is characterized by excessive production of extracellular matrix (ECM) or inhibition of ECM degradation. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) proteinases, which are widely presented in mammals, have very critical roles in ECM remodelling. We aimed to study the role of ADAMTS proteinases and some of the ECM markers in the pathogenesis of renal fibrosis and to investigate the effects of hypoxia on these biomarkers. Methods In addition to the control group, Adriamycin (ADR) treated rats were divided into four groups as ADR, sham and two hypoxia groups. Renal nephropathy was assessed biochemical assays, pathological and immunohistochemical staining methods. The expression of ADAMTSs and mRNA were determined using Western blotting and real-time PCR, respectively. Results Renal dysfuntion and tissue damage in favour of ECM accumulation and renal fibrosis were observed in the ADR group. This was approved by remarkable changes in the expression of ADAMTS such as increased ADAMTS-1, -12 and -15. In addition, it was found that hypoxia and duration of hypoxia enhanced markers of tubulointerstitial fibrosis in the rat kidney tissues. Also, expression differences especially in ADAMTS-1, -6 and -15 were observed in the hypoxia groups. The variable and different expression patterns of ADAMTS proteinases in the ADR-induced renal fibrosis suggest that ADAMTS family members are involved in the development and progression of fibrosis. Conclusion The expression changes of ADAMTS proteinases in kidney and association with hypoxia have potential clues to contribute to the early diagnosis and treatment options of renal fibrosis.Öğe Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage(Galenos Publ House, 2015) Turamanlar, Ozan; Ozen, Oguz Aslan; Songur, Ahmet; Yagmurca, Murat; Akcer, Sezer; Mollaoglu, Hakan; Aktas, CevatBackground: Alpha lipoic acid is a potent antioxidant that plays numerous roles in human health. This study examined the effect of ALA on rat sciatic nerve ischemia reperfusion damage. Aims: Protective effect of alpha lipoic acid (ALA) on sciatic nerve following ischemia-reperfusion in rats was investigated by using light microscopy and biochemical methods. Provided that the protective effect of ALA on sciatic nerve is proven, we think the damage to the sciatic nerve that has already occurred or might occur in patients for various reasons maybe prevented or stopped by giving ALA in convenient doses. Study Design: Animal experiment. Methods: Forty-two adult male Sprague-Dawley rats (250-300 grams) were used in this study. Rats were randomly divided into six groups including one control (Group 1), one sham (Group 2), two ischemia-reperfusion (Groups 3 and 4) and two treatment groups (Groups5 and 6). Doses of 60 and 100 mg/kg ALA were given (Group 5 and 6) intra peritoneally twice, 1 and 24 hours before the ischemia to each treatment group. Ischemia was carried out the abdominal aorta starting from the distal part of the renal vein for two hours followed by reperfusion for three hours. In immunohistochemical methods, fibronectin immunoreactivity was analyzed. For biochemical analyses, the tissues were taken in eppendorf microtubes and superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) enzyme activities as well as malondialdehyde (MDA) and nitricoxide (NO) levels were measured. Results: Fibronectin was observed to have increased significantly in the ischemia group; on the other hand, it was observed to have decreased in parallel to the doses in the ALA groups. Biochemical studies showed that SOD and GSHPx declined with ischemia-reperfusion, but the activities of these enzymes were increased in the treatment groups in parallel with the dose. It was found that increased MDA levels with ischemia-reperfusion were decreased in parallel with ALA dose. There were no statistically significant changes in NO. Conclusion: Increased fibronectin observed after ischemia/reperfusion of rat sciatic nerve is reduced after the administration of ALA. This indicates that the function of fibronectin, to reconnect cut nerve segments and regenerate nerves, is more prominent than its function in tissue healing after ischemia. ALA administered before ischemia decreases MDA and increases SOD and GSHPx. We think that ALA may protect against the pathological changes in ischemic nerve and may be used to devise more efficient treatments.Öğe Protective Effect of Melatonin on Infrarenal Aortic Occlusion: This Effect Is Related to Anti-inflammatory Effect and Antioxidant Effect(Springer/Plenum Publishers, 2014) Ahsen, Ahmet; Gonul, Yucel; Genc, Abdurrahman; Ulu, Memnune Sena; Yagmurca, Murat; Kocogullari, Cevdet Ugur; Celik, Sefa[Abstract Not Available]
