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Background and Objectives: The most common kidney stones are calcium stones and calcium oxalate (CaOx) stones are the most common type of calcium stones. Hyperoxaluria is an essential risk factor for the formation of these stones. Quercetin is a polyphenol with antioxidant, anti-inflammatory, and many other physiological effects. The aim of this study was to investigate the protective effect of quercetin in hyperoxaluria-induced nephrolithiasis. Materials and Methods: Male Wistar-Albino rats weighing 250–300 g (n = 24) were randomized into three groups: Control (n = 8), ethylene glycol (EG) (n = 8), and EG + quercetin (n = 8). One percent EG-water solution was given to all rats except for the control group as drinking water for five weeks. Quercetin-water solution was given to the EG + quercetin group by oral gavage at a dose of 10 mg/kg/day. Malondialdehyde (MDA), catalase (CAT), urea, calcium, and oxalate levels were analyzed in blood and urine samples. Histopathological assessments and immunohistochemical analyses for oxidative stress and inflammation indicators p38 mitogen-activated protein kinase (p38-MAPK) and nuclear factor kappa B (NF-kB) were performed on renal tissues.&nbsp, Results: The MDA levels were significantly lower in the quercetin-treated group than in the EG-treated group (p = 0.001). Although CAT levels were higher in the quercetin-treated group than the EG-administered group, they were not significantly different between these groups. The expression of p38 MAPK was significantly less in the quercetin-treated group than the EG group (p &lt, 0.004). There was no statistically significant difference between the quercetin and EG groups in terms of NF-kB expression.&nbsp, Conclusions: We conclude that hyperoxaluria activated the signaling pathways, which facilitate the oxidative processes leading to oxalate stone formation in the kidneys. Our findings indicated that quercetin reduced damage due to hyperoxaluria. These results imply that quercetin can be considered a therapeutic agent for decreasing oxalate stone formation, especially in patients with recurrent stones due to hyperoxaluria.

Like several other anticancer drugs, methotrexate (MTX) causes side effects, such as neuropathic pain, hepatotoxicity, and nephrotoxicity. Abnormal production of reactive oxygen species has been suspected in the pathophysiology of MTX-induced hepatorenal toxicity. Therefore, the aim of this study was to investigate the probable protective role of vitamin C (Vit C) on oxidative stress induced by MTX in the liver and kidney tissues of rats. A total of 32 rats were randomly and equally divided into four groups. The first group served as the control group. The second group received a single dose of 20 mg/kg of MTX intraperitoneally. To demonstrate our hypothesis, the third and the fourth groups received 250 mg/kg of Vit C for 3 days by oral gavage, with or without MTX treatment. At the end of the study, the liver and kidney tissues of the rats were collected and examined using histology. Both the tissues were assayed for malondialdehyde concentration and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. In hepatic and renal tissues, lipid peroxidation levels were increased, whereas SOD, CAT, and GSH-Px levels were decreased by MTX. All parameters, including CAT levels in hepatic tissue, were significantly restored after the administration of Vit C for 3 days. Similar to the biochemical findings, evidence of oxidative damage was examined in both types of tissues by histopathological examination. From the results of this study, we were able to observe that Vit C administration modulates the antioxidant redox system and reduces the renal and hepatic oxidative stress induced by MTX. Vit C can ameliorate the toxic effect of MTX in liver and kidney tissues of rat.

Resveratrol (RES) is a polyphenol with antioxidant, anti-inflammatory, and many other physiological effects on tissues. In the present study, the effect of resveratrol in hyperoxaluria driven nephrolithiasis/nephrocalcinosis is investigated. Wistar-Albino rats of 250–300 g (male, n = 24) were included in the present study. The rats were randomized into three groups: Group 1 consisted of the controls (n = 8), Group 2 of hyperoxaluria (1% ethylene glycol (EG), n = 8), and Group 3 of the treatment (1% EG + 10 mg/kg of RES, n = 8) group. At the beginning and fifth week of the study, two rats from each group were placed in metabolic cages for 24 h and their urine was collected. At the end of the study, the rats were killed and their blood was collected from the vena cava inferior. The right kidneys of the rats were used for biochemical and the left ones for immunohistochemical analyzes. Malondialdehyde (MDA), catalase, urea, calcium, oxalate, and creatinine clearance were studied in the blood, urine, and kidney tissues. Moreover, routine histological evaluation, and p38-MAPK and NFkB immunohistochemical analyses were conducted. In the hyperoxaluria group, urinary oxalate levels were higher than the control group; yet, lower in the treatment group compared to hyperoxaluria group (p

Curcumin has anti-inflammatory and antioxidant effects and is reported to have many biologic activities. The current study examines effect of curcumin on: 1) systemic T helper 17 (Th17) cell response; 2) gingival expressions of interleukin (IL)-17 and retinoic acid receptor-related orphan receptor (ROR) γt; and 3) alveolar bone loss (ABL) in experimental periodontitis.Thirty-eight male albino Wistar rats were divided into four groups: 1) group 1 = periodontitis; 2) group 2 = periodontitis with curcumin treatment; 3) group 3 = periodontally healthy with curcumin treatment; and 4) group 4 = periodontally healthy. Curcumin was administered via oral gavage (30 mg/kg/d) for 15 days. After sacrifice via exsanguination, the following serum levels were determined using enzyme-linked immunosorbent assay: 1) IL-1β; 2) IL-6; 3) IL-17A; 4) IL-23; and 5) transforming growth factor- β. Morphometric evaluation of ABL was conducted and expression levels of IL-17 and RORγt in gingival tissues were evaluated immunohistochemically.Group 2 had significantly lower ABL than group 1 (P0.0125). Highest expression levels of IL-17 and RORγt were observed in group 1 and were significantly higher than those in all other groups (P0.0125). The only serum biochemical parameter significantly different among groups was level of IL-23 (P0.05). Serum IL-23 levels were higher in groups 1 and 2 than groups 3 and 4 (P0.0125); however, they were not significantly different for groups 1 and 2 (P0.0125).Curcumin seems to be a promising host modulatory agent in periodontal disease pathogenesis regarding IL-17/IL-23 axis, with a decreasing effect on ABL and gingival expressions of IL-17 and RORγt.

The aim of the current study was to investigate the probable protective effects of Pentoxifylline (PTX) and Alpha Lipoic Acid (ALA), which display anti-oxidative efficacy against hepatotoxicity and nephrotoxicity, those being the major side effects of Methotrexate (MTX). Rats were divided into four groups: a control group; MTX (20mg/kg/day) group; MTX+PTX (20mg/kg/day+50mg/kg/day) group; and an MTX+ALA (20mg/kg/day+100mg/kg/day) group. At the end of the experiment, biochemical, histochemical and immunohistochemical analyses were performed on liver and kidney tissues of rats. We determined Glutathione Peroxidase (GSH-Px), Superoxide Dismutase (SOD), Catalase (CAT), Malondialdehyde (MDA), Nitric Oxide (NO) and Xanthine Oxidase (XO) levels in the liver and kidney. Moreover, Gamma Glutamyl Transferase (GGT), Direct Bilirubin (DBil), Blood Urea Nitrogen (BUN), and urea levels were measured in the serum. The histochemical evaluation revealed a significant decrease in MTX caused damage in the PTX- and ALA-treated groups (especially in ALA group). On the other hand, the immune staining of iNOS and TNF-α were observed most densely in the MTX group, while the density decreased in the PTX- and ALA-administered groups. We determined increased GGT, BUN, urea and levels of CAT, MDA, NO, and XO values in both groups, while GSH-Px (an increase in liver tissue) and DBil levels were decreased in the group that received MTX. However, we determined decreased SOD levels in liver tissue. In the PTX and ALA groups, the levels of GGT, BUN and urea as well as the levels of CAT, MDA, NO and XO decreased (SOD increased in the liver tissue), and the levels of GSH-Px and DBil increased. In conclusion, it can be stated that, although ALA is more effective in preventing the toxic effects of MTX on the liver and kidney, PTX also has a preventive effect. As a result, we can readily suggest that ALA and PTX can have protective effects by decreasing MDA, NO, BUN and urea values as antioxidants against MTX-induced damage in liver and kidney of rats.

Amaç: Fosfatlı gübrelerde, deterjanlarda ve rafine petrol türevlerinde bulunan kadmiyum, 1817 yılında keşfedilmiş toksik ağır bir metaldir ve sigaranın majör bileşenlerinden biridir. Selenyum serbest radikallerin üretimini azaltmak ve önlemek için gerekli olan, doymamış yağ asitlerinden türeyen ve peroksitleri yok ettiği düşünülen bir elementtir. Melatonin, pineal bezin majör hormonudur. Organizma, serbest radikallerin neden olduğu hücre hasarını önlemek için antioksidan savunma sistemi geliştirir. Bu çalışmada, kadmiyumun vücutta dokularda birikerek oluşturduğu toksisite üzerine Selenyum (Se) ve Melatoninin etkisinin belirlenmesi amaçlandı. Gereç-Yöntem: Deney grupları; her grupta 8 dişi sıçan olmak üzere, kontrol (Grup I), Kadmiyum (Grup II), Melatonin (Grup III), Selenyum (Grup IV), Kadmiyum+Melatonin (Grup V), Kadmiyum+Selenyum (Grup VI), Melatonin+Selenyum (Grup VII) ve Kadmiyum+Melatonin+Selenyum (Grup VIII) şeklinde düzenlendi. Kadmiyum (2 mg/kg/gün; gavajla), Melatonin (3 mg/kg/gün; intraperitoneal) 30 gün boyunca günde bir kez, selenyum ise 5'er gün arayla 30 günde 6 kez uygulandı. Deney sonunda over, tuba uterina ve uterus dokuları alınarak, bir kısmı histokimyasal ve immünohistokimyasal değerlendirme için %10'luk nötral formaldehit içerisine, diğer kısmı ise biyokimyasal çalışma için fosfat tamponu içerisine ve kan örnekleri apopitotik hücre ve DNA fragmantasyonu tayini için EDTA'lı tüplere alındı. Bulgular, Sonuç ve Tartışma: Çalışmamızın sonunda kadmiyum verilmesine bağlı olarak over, tuba uterina ve uterus dokularında MDA düzeyleri kontrol grubuna göre artış gözlendi. GSPx ve CAT aktivite değerlerinde de artış saptandı. Grup III, VII ve VIII' de benzer parametreler gözlendi. Grup V ve VI' da ise antioksidanların etkisi ile lipid peroksidasyon engellenerek MDA, GSPx ve CAT düzeylerinin kadmiyuma göre düştüğü tespit edildi. DNA ladder kit ile yapılan analizler sonucunda sadece kadmiyum verilen grupta DNA fragmantasyonu ve buna bağlı olarak apopitotik hücre artışı gözlendi. Histolojik ve immünohistokimyasal bulgularımızda biyokimyasal analizler ve DNA ladder değerlerine paralel sonuçlar elde edildi. Kadmiyum grubunun bütün dokularında hasar (overlerin foliküllerinde dejenerasyon, hemorajik alanlar, mononükleer hücre infiltrasyonu ve bağ dokusu artışı; tuba uterina'nın epitelinde dejenerasyon ve tübüllerinde dejenerasyon; uterusun epitelinde dejenerasyon, endometriyum tabakasında dilate alanlar ve endometriyal bezlerde dejenerasyon), E-kaderin, NCAM sentezinde artış ve dokularda yüksek MT-3 birikimi gözlendi. Grup VI ve VIII' de anlamlı histopatolojik düzelmeler gözlemlendi, ancak grup V'te herhangi bir düzelme tespit edilemedi. Kadmiyumun dişi genital sistem organlarında hasar meydana getirdiğini, selenyumun dokuları bu hasardan korurken Melatoninin herhangi bir koruyucu ya da düzeltici etkisi olmadığı gözlendi. Melatoninin koruyucu bir etki gösterememesinin sebebini dişi sıçanların hormonal değişimlerine ve Melatoninin uzun süreli kullanımına bağlı olabileceği düşünüldü. Çalışmamızın kadmiyum tedavisine ya da korumasına katkı sağlamasını ve yeni tedavi yollarına basamak teşkil etmesini umuyoruz. Aim: Cadmium which is discovered in 1817 is a toxic heavy metal and found in phosphate fertilizers, detergents and refined petroleum and it's one of the major components of cigarette smoking. Selenium is an element, derived from unsaturated fatty acids, thought to degrade peroxides and needed to reduce - prevent the production of free radicals. Melatonin is the major hormone of the pineal gland and it is develops an antioxidant defense system to prevent cell damage caused by free radicals in organism. In our study, it was aimed to determine whether Selenium and Melatonin show antioxidant properties on the toxicity that cadmium accumulates on tissues in the body. Material Method: Experimental groups; Control (Group I), Cadmium (Cd) (Group II), Melatonin (Group III), Selenium (Group IV), Cadmium+Melatonin (Group V), Cadmium+Selenium (Group VI), Melatonin+Selenium (Group VII) and Cadmium + Melatonin + Selenium (Group VIII) were arranged to be8 female rats in each group. Cadmium (2 mg / kg / daywith gavage), Melatonin (3 mg / kg / day, intraperitoneal)30 days were applied once a day and seleneium wasapplied 6 times in 30 days, 5 days a day. At the end ofthe experiment, over, tuba uterine and uterus tissues weretaken. Some of the receiving tissues were in 10% neutralformaldehyde for histochemical and immunohistochemicalevaluation and the other were in phosphate buffer forbiochemical study and bloods were taken into the EDTAtube for apoptotic cell and DNA fragmentation assay.Results and Discussion: At the end of our study, MDAlevels were increased in the over, tubal uterine anduterine tissues according to the cadmium administrationgroup and also increase in GSPx and CAT activity valueswas detected, similar parameters were also observed ingroup III, group VII, group VIII. But in group V and groupVI, were found to inhibit lipid peroxidation of antioxidantsand decrease MDA, GSPx and CAT levels comparedto cadmium. As a result of the analysis with DNA ladderkit, DNA fragmentation and consequently apoptotic cellsnumber were observed only in the cadmium-administeredgroup. Histological and immunohistochemical findingsgave parallel results to biochemical analyzes and DNAladder values. in all the tissues of the cadmium group were observed; High MT-3 accumulation, damage (degeneration of ovarian follicles, haemorrhagic areas, mononuclear cell infiltration and increased connective tissue; degeneration in tuba uterina epithelium and degeneration in tubules; degeneration in the uterine epithelium, dilate fields in the endometrium layer and degeneration in the endometrial glands) and increase in E-cadherin, NCAM synthesis. When significant improvements were observed in group VI and group VIII, there were no improvement in the group V. We have seen that cadmium brings damage to the female genital system organs and while selenium has protective effect for tissues from this damage, Melatonin has not a protective or corrective effect but we think, the cause of this event because of to hormonal changes of female rats and the long-term use of Melatonin. At last, we hope that our work will contribute to cadmium treatment or protection and will provide a stepping stone to new ways of treatment.

Background: Silibinin is a bioactive flavonolignan extracted from milk thistle, known as Silybum marianum. Silibinin exerts strong antiproliferative, proapoptotic, and anti-inflammatory effects. Many studies have shown that silibinin inhibits experimentally induced malignancies of the liver, prostate, skin, and colon as well as promotes inhibition of the proliferation of cancer cell lines in vitro. This study aimed to investigate the effects of silibinin on the human breast carcinoma cell lines MDA-MB-231 and MCF-7 in monolayer and spheroid cultures. Method: The MDA-MB-231 and MCF-7 cell lines were cultured in both monolayer and spheroid cultures. Cells were treated with silibinin at 24, 48, and 72 h of incubation. The 5-bromo-2′-deoxyuridine labeling index was used to determine the cells of the synthesis phase. Poly-ADP-ribose-polimerase immunohistochemical staining and the terminal deoxynucleotidyl transferase dUTP nick and labeling assay were used to determine the death of cells in both the monolayer and spheroid cultures. Results: An half maximal inhibitory concentration dose of silibinin in MDA-MB-231 and MCF-7 cells was 100 µM/mL at 24, 48, and 72 h of incubation. Terminal deoxynucleotidyl transferase dUTP nick and labeling positive cells and active poly-ADP-ribose-polimerase were detected after treatment with silibinin in both the monolayer and spheroid cultures. The dead cell count was higher in the MDA-MB-231 and MCF-7 cell lines with silibinin applied than in the controls. Conclusions: Our study demonstrated that silibinin applications enhanced terminal deoxynucleotidyl transferase dUTP nick and labeling positive cells and active poly-ADP-ribose-polimerase in comparison to the control in both the monolayer and spheroid cultures.

The aim of this study was to evaluate the role of α-lipoic acid (α-LA) on oxidative damage and inflammation that occur in endothelium of aorta and heart while constant consumption of high-fructose corn syrup (HFCS). The rats were randomly divided into three groups with each group containing eight rats. The groups include HFCS, HFCS + α-LA treatment, and control. HFCS was given to the rats at a ratio of 30% of F30 corn syrup in drinking water for 10 weeks. α-LA treatment was given to the rats at a dose of 100 mg/kg/day orally for the last 6 weeks. At the end of the experiment, the rats were killed by cervical dislocation. The blood samples were collected for biochemical studies, and the aortic and cardiac tissues were collected for evaluation of oxidant–antioxidant system, tissue bath, and pathological examination. HFCS had increased the levels of malondialdehyde, creatine kinase MB, lactate dehydrogenase, and uric acid and showed significant structural changes in the heart of the rats by histopathology. Those changes were improved by α-LA treatment as it was found in this treatment group. Immunohistochemical expressions of tumor necrosis factor α and inducible nitric oxide synthase were increased in HFCS group, and these receptor levels were decreased by α-LA treatment. All the tissue bath studies supported these findings. Chronic consumption of HFCS caused several problems like cardiac and endothelial injury of aorta by hyperuricemia and induced oxidative stress and inflammation. α-LA treatment reduced uric acid levels, oxidative stress, and corrected vascular responses. α-LA can be added to cardiac drugs due to its cardiovascular protective effects against the cardiovascular diseases.

Amikacin (AK) is an antibacterial drug, but it has remarkable nephrotoxic and ototoxic side effects due to increase in reactive oxygen radicals. This study was established to determine the possible protective effects of alpha-lipoic acid (ALA), a powerful antioxidant, on AK-induced nephrotoxicity. Three different groups of rats (n = 6) were administered saline (control), AK (1.2 g/kg, intraperitoneally), ALA (100 mg/kg, p.o.) and AK combination (ALA one day before the AK for five days). Renal function, oxidative stress markers and histological changes were evaluated at the end of the experiment. Malondialdehyde was increased as an indicator of free radical formation in AK-induced group and decreased with ALA treatment. While catalase activity was increased significantly, superoxide dismutase and glutathione peroxidase activities were not statistically significant increased with ALA treatment. The result showed that AK enhanced levels of urea, creatinine and blood urea nitrogen in serum significantly. Administration of ALA reduced these levels of biochemical markers. Histopathological observations were confirmed by biochemical findings. In conclusion, ALA is suggested to be a potential candidate to ameliorate AK-induced nephrotoxicity.

The purpose of this study was to provide a morphologic description and assessment on the formation level of the sural nerve (SN) and its components. Also we aimed to reveal histological features of the SN components. An anatomical study of the formation of the SN was carried out on 100 limbs from 50 embalmed foetuses. The results showed that the SN was formed by the union of the medial sural cutaneous nerve (MSCN) and the peroneal communicating branch (PCB) in 71% of the cases (Type A); the MSCN and PCB are branches of the tibial and common peroneal nerve (CPN) or lateral sural cutaneous nerves (LSCN), respectively. Formation level of the SN was at the distal third of the leg in 43% of the cases, at the middle third of the leg in 46% of the cases, and at the upper third of the leg in 11% of the cases. The PCB originated in the CPN in 68% and the PCB originated in the LSCN in 3% of the cases. The SN was formed only by the MSCN in 20% of the cases (Type B). Type C was divided into four subgroups: in the first group the PCB and fibres of the posterior femoral cutaneous nerve joined the MSCN in 4% of cases; in the second group the MSCN, PCB, and sciatic nerve did not unite and coursed separately in 1% of cases; in the third group the SN arose directly from the sciatic nerve alone and the MSCN made a little contribution in 2% of cases; and in the fourth group the PCB, fibres of the sciatic nerve, and the MSCN formed the SN in 1% of the cases. The SN was formed only by the PCB in 1% of the cases (Type D). Distances of the formation level of the SN to the intercondylar line and the lateral malleolus were measured and also noted. A detailed knowledge of the anatomy of the SN and its contributing nerves are important in many interventional procedures.

Cisplatin (CP) is a potent anticancer drug. However, it has side effects on kidney such as nephrotoxicity. Abnormal production of reactive oxygen species (ROS) has been accused in the etiology of CP-induced nephrotoxicity. Several ROS scavengers have been reported to prevent nephrotoxicity after CP administration. In this study, we used prostaglandin E1 (PGE1) analogues misoprostol (MP) to reduce this damage. MP has gained considerable interest as a ROS scavenger. Rats were received a single injection of CP (5 mg/kg, i.p.) with or without MP pretreatment (200 mcg/kg, orally). The renal tissue morphology was investigated by light microscopy. Trunk blood was also obtained to determine lipid peroxidation product malondialdehyde (MDA) and activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT). CP administration increased MDA production and decreased SOD and CAT levels in the kidney tissue when compared to the control group. Morphological damage in CP administrated rats was also severe in the kidney tissue. MP treatment after CP application protected the renal tissues from CP’s side effect. These findings indicate that MP has beneficial effects on CP induced nephrotoxicity in rats.

Tez (Yüksek Lisans) -- İstanbul Teknik Üniversitesi, Fen Bilimleri Enstitüsü, 2008, Thesis (M.Sc.) -- İstanbul Technical University, Institute of Science and Technology, 2008, Yapılan bu çalışmada belirli şartnamelerin esaslarına göre EXCEL programı ile çeşitli sıvılaşma analizi yöntemlerinin birlikte değerlendirildiği bir program hazırlanmıştır., In this study, by using the standarts, and by using the EXCEL programme, liquefaction analyses programmed which evaluates various liquefaction criteria., Yüksek Lisans, M.Sc.