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Öğe The Ameliorate Effects of Nerolidol on Thioacetamide-induced Oxidative Damage in Heart and Kidney Tissue(2022) Türkmen, Neşe Başak; Yüce, Hande; Taşlıdere, Aslı; Şahin, Yasemin; Çiftci, OsmanObjectives: Thioacetamide (TAA) is an organosulfur, white crystalline compound having liver injury. However, it shows toxic effects on many organs. The reverts the oxidative stress created by TAA on the heart and kidney, and decreased lipid peroxide peroxidation back with antioxidant- properties nerolidol (NRL). This study hypothesized that NRL treatment a potential ameliorate nephrotoxicity and cardiotoxicity caused by TAA. Materials and Methods: Thirty-two Wistar Albino male rats (3-4 months old and 280-300 g in weight) were divided into four groups. (a) Control, (b) TAA was administered 200 mg/kg i.p. twice a weekly (c) NRL was orally administered at the dose of 100 mg/kg per every other day by gavages. (d) TAA and NRL-treated groups were assigned 200 mg/kg TAA and 100 mg/kg NRL for three weeks. Results: As a result of these dose administration thiobarbituric acid reactive substances (TBARS) levels, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx) levels were detected. The results were shown that TAA leads to a significant rise in TBARS level and a significant decrease in GPx, CAT, SOD, and GSH levels in the heart and kidney tissue according to the control group. The finding of this study the NRL treatment reduced TBARS levels and increased antioxidant level. Administration of NRL prevents the biochemical and histopathological alterations induced by TAA. Conclusion: The findings of this study show that the antioxidant activity of NRL can protect against biochemical and histological damage caused by TAA in heart and kidney tissue.Öğe Assessment of sertraline activity in a vasospasm model following experimentalsubarachnoid haemorrhage(2020) Kıyak, Veysel; Öztanır, Mustafa Namık; Türkmen, Neşe Başak; Taşdemir, Aslı; Çiftçi, OsmanVasospasm following subarachnoid haemorrhage (SAH) is a process yet to be fully clarified in terms of its aetiology and results. According to one of the many theories about vasospasm developing after SAH, the process results from an increase of pro-inflammatory agents and decrease in antioxidant agents. Other hand experimental studies on rats found a significant decrease in the pro-inflammatory parameters TNF-? and IL-1? in the blood values obtained after the use of sertraline. In this study, the findings regarding the effectiveness of sertraline in the treatment of vasospasm developing an experimental SAH model are presented. In this study, adult males of Spraque-Dawley breed, not used in any previous study and weighing between 250–350 g, were used. Rats were divided into 4 groups with the control group (n=5) and other groups (n=6 in each). Group 1 was the control, and Group 3 was the sertraline group. In Groups 2 and 4, SAH was initiated by giving rats autologous arterial blood in the cisterna magna. The tissues were examined in terms of mononuclear cell infiltration, vascular congestion, and neuron degeneration. In the experimental SAH model based on these values, it was found that the use of sertraline significantly reduced mononuclear cell infiltration, vascular congestion, and neuron degeneration. Moreover, in animal studies, it was shown that SSRIs increased neurogenesis and release of neurotrophins from the hippocampus. In our study, it was concluded that sertraline was effective in dissolving vasospasm in the experimental SAH model. However, we further believe that more experimental studies to investigate other SSRI compounds of the same family can contribute to the knowledge and understanding of this process.Öğe Chrysin prevents brain damage caused by global cerebralischemia reperfusion in a C57BL J6 mouse model(Turkısh journal of medıcal scıences, 2016) Durak, Mehmet Akif; Öztanır, Mustafa Namık; Türkmen, Neşe Başak; Çiftçi, Osman; Taşlıdere, Aslı; Tecellioğlu, Mehmet; Önder, ArifThe present study investigated the neuroprotective effects of chrysin (CRS) following global cerebral ischemia and reperfusion (I/R) in a C57BL/J6 mouse model. Materials and methods: A total of 40 mice were equally divided into four groups: (1) sham-operated (SH = control), (2) global cerebral I/R (I/R), (3) CRS, and (4) CRS + I/R. In the I/R group, the bilateral carotid arteries were clipped for 15 min and the mice were treated with vehicle (corn oil) for 10 days. In the CRS group, CRS (50 mg/kg) was given for 10 days without carotid occlusion. In the CRS + I/R group bilateral carotid arteries were clipped for 15 min and the mice were also treated with CRS (50 mg/kg) for 10 days. All of the rats were sacrificed under anesthesia on day 10, and neurodegenerative histological changes in the brain and tissue levels of oxidants and antioxidants were evaluated. Results: CRS treatment significantly reversed the oxidative effects of I/R and inhibited the development of neurodegenerative histopathologies. In the CRS + I/R group, the decrease in TBARS levels and increase in GSH levels were similar to those in the SH group. Conclusion: Treatment with CRS can positively affect the neural system of mice and it can be used for the treatment of global cerebral I/R.Öğe Dose dependent cytotoxic activity of patulin on neuroblastoma, colon and breast cancer cell line(2021) Türkmen, Neşe Başak; Yüce, Hande; Ozek, Dilan Askin; Aslan, Sumeyye; Yaşar, Şeyma; Ünüvar, SongülAim: Patulin, a mycotoxin, is an organic compound classified as a polypeptide. Patulin, which is generally detected in moldy fruits and their derivatives, has been suggested to have anticancer activity. Some studies have shown that it induces apoptosis in the cell. This study aims to investigate the anticancer activity of patulin in SH-SY5Y (human neuroblastoma cell line), HCT116 (human colon cancer cell line), and MCF-7 (human breast cancer cell line) cell lines. Materials and Methods: SH-SY5Y, HCT116, MCF-7, and L929 (healthy fibroblast) cell lines were used for cytotoxicity experiments. Cells were added in 96-well plates at 5x103 cells per well. Serial dilutions of patulin at a dose of 1, 2.5, 5, 10, 25, 50, and 100 µM were added to the waiting cells in 24 hours incubation. All cell lines were exposed to patulin for 24 and 48 hours. The cytotoxic activity of patulin in cancer and healthy cell lines was determined in vitro by the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2- (4-sulphophenyl)-2H-tetrazolium) cell viability test. The results of the toxicity tests were measured spectrophotometrically (450 nm) in ELISA at intervals of 24 hours for 2 days. Results: Patulin caused cytotoxic activity in all cell lines at a concentration of 100 µM. Patulin showed cytotoxic activity at low doses only in the SH-SY5Y cell line. At doses of 25 and 50 µM, HCT116 caused more than 50% death in the cell line, while higher concentrations induced cell death in the MCF-7 cell line. Conclusion: Patulin showed anticancer activity at high concentrations in colon and breast cancer cell lines, and both low and high concentrations in the SH-SY5Y cell line. Patulin may be a new candidate molecule in the treatment of neuroblastoma, colon, and breast cancers, depending on the dose.Öğe Drug-Drug Interaction of Aldehyde Oxidase Inhibitor and Xanthine Oxidase Inhibitor with Favipiravir(2022) Ozek, Dilan Askin; Keskin, Zeliha; Yüce, Hande; Türkmen, Neşe Başak; Aslan, Sumeyye; Ünüvar, SongülAim: Favipiravir is an effective antiviral used in the treatment of COVID-19. It is metabolized by aldehyde oxidase (AO) and xanthine oxidase (XO). This study investigated drug-drug interactions between favipiravir with both AO substrate and XO enzyme inhibitor, allopurinol, and an XO inhibitor, verapamil. Material and Methods: 25 Sprague-Dawley female rats, 250-300 g, were divided into five equal groups. Blood samples were taken from the jugular vein at the end of 0, 15, 30, and 45 minutes, and at the end of the 1st, 2nd, 4th, 6th, and 8th hours after the drugs were administered. The drug-blood concentration was determined in the HPLC-UV device using plasma. The ELISA method measured AO and XO enzyme activities in rat liver tissue. Results: Allopurinol prolonged the time taken for favipiravir to reach Cmax (Tmax), decreased maximum serum concentration (Cmax), elimination half-life (T1/2), area under the curve (AUC), and mean residence time (MRT). Allopurinol significantly reduced clearance per unit time (Cl/f) when co-administered with favipiravir. Verapamil accelerated the elimination of favipiravir, significantly reducing T1/2, MRT, and AUC. On the other hand, Favipiravir decreased the absorption of verapamil and slowed its elimination. Cmax, AUC, and Cl values of verapamil decreased. In addition, T1/2, MRT, and volume of distribution (Vd) increased. Conclusion: In conclusion, the concomitant use of favipiravir with other drugs that affect AO and/or XO enzyme activities may cause changes in the pharmacokinetic profiles of drugs and the levels of enzymes that metabolize drugs.Öğe The inhibition of Src kinase suppresses the production of matrix metalloproteinases in from synovial fibroblasts and inhibits MAPK and STATs pathways(2021) Yalçın Kehribar, Demet; Özgen, Metin; Yolbaş, Servet; Yıldırım, Ahmet; Türkmen, Neşe Başak; Onalan, Ebru; Çiftci, Osman; Özercan, İbrahim Hanifi; Koca, Süleyman S.Abstract: Background/aim: The purpose of this study was to investigate the antiarthritic potentials of the inhibition of Src kinase in vivo and in vitro settings. Materials and methods: Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund’s adjuvant (collagen induced arthritis [CIA] model) in Wistar albino rats. One day after the onset of arthritis, dasatinib, a potent Src kinase inhibitor, (5 mg/kg/day) was given via oral gavage. Tissue Src, Fyn, MAPK and STAT mRNA expressions were determined by real-time polymerase chain reaction. On the other hand, fibroblast like synoviocytes (FLSs) were harvested patients with rheumatoid arthritis (RA) undergoing surgical knee joint replacement. FLSs were stimulated with cytokines and dasatinib was added in different concentrations. MMP –1, –3, and –13 levels in FLSs culture were determined by ELISA. Results: The tissue mRNA expressions of Src, Fyn, MAPK and STATs were increased in the arthritis CIA group compared to the control group. Their mRNA expressions in the CIA + dasatinib group were decreased and similar in the control group. In in vitro setting, MMP –1, –3, and –13 expressions from FLSs induced by IL-1? and TNF-? were increased, while dasatinib suppressed their productions from FLSs. Conclusion: The present study shows that the inhibition of Src kinase has antiarthritic potentials in both in vivo and in vitro settings. Src kinase inhibition may be candidate to further research in human RA. Key words: Rheumatoid arthritis, collagen induced arthritis, src kinase, matrix metalloproteinaseÖğe Pembrolizumab verilen sıçanlarda olası testis toksisitesine karşı aromataz inhibitörlerinin etkisi(İnönü Üniversitesi, 2019) Türkmen, Neşe BaşakAmaç: Pembrolizumab (PEMB) PD-1'i bloke eden monoklonal antikor olup etkili bir immunoterapi ilacıdır. Anastrazol (ANAST) infertilite önleyici bir aromataz inhibitörüdür. Benzer şekilde resveratrol (RES) de üreme sisteminde etkili antioksidan bir polifenol olup, doğal aromataz inhibitörü olarak işlev görmektedir. Bu çalışma, PEMB ile oluşturulmuş reprodüktif hasara karşı ANAST ve RES'in koruyucu etkilerini göstermek amacıyla planlanmıştır. Materyal ve Metot: Çalışmada 42 adet Sprauge-Dawley cinsi sıçan kullanıldı. Sıçanlar randomize olarak 6 eşit gruba ayrıldı (n=7); Kontrol, PEMB, PEMB +ANAST, PEMB+RES, RES, ANAST şeklindedir. 30 günlük deney sonunda sıçanlar ketamin-ksilazin anestezisi altında sakrifiye edildi. Sıçanlardan biyokimyasal ve histolojik değerlendirmeler için testis doku örnekleri alındı. Histolojik analizler için dokular rutin doku takip işlemlerinden geçirildi. Biyokimyasal olarak TBARS, GSH, CAT, SOD, GSH-Px düzeyleri spektrofotmetrik olarak ölçüldü. Spermatolojik olarak sperm hareketliliği, anormal sperm oranı ve epididimal sperm konsantrasyonu incelendi. Elisa yöntemi kullanılarak serum Testosteron ve PD-1 düzeyleri ölçüldü. Bulgular: Laboratuvar analizleri sonucunda PEMB verilen sıçanlarda TBARS düzeyinin anlamlı şekilde arttığı, GSH, SOD, GPx ve CAT düzeylerinin ise azaldığı belirlendi. ANAST ve RES uygulamasının oluşan bu değişimleri tersi yönde değiştirdiği belirlendi. Histolojik açıdan; H-E boyama yöntemi ile kontrol, ANAST ve RES grupları testis örnekleri normal histolojik görünümde izlendi. PEMB grubunda testis dokusunda seminifer tübül yapılarında histolojik hasar saptandı. PEMB+RES ve PEMB+ANAST gruplarında ise bu histolojik hasarda azalma olduğu tespit edildi. Spermatolojik analiz deneylerinde sperm kalitesi ve üreme performansı tespit edildi. Bunun dışında PD-1 ve testosteron seviyelerine Elisa yöntemiyle bakılarak tez desteklendi. Sonuç: PEMB ile oluşturulan reprodüktif hasara karşı ANAST ve RES'in tedavi edici etkileri olduğu belirlendi. Anahtar kelimeler: Pembrolizumab, Testis, Anastrazol, ResveratrolÖğe THE PROTECTIVE EFFECTS OF TETRANDRINE AGAINST TO HISTOLOGICAL, SPERMATOLOGICAL AND OXIDATIVE DAMAGE INDUCED BY AROCLOR 1254 ON THE MALE RATS REPRODUCTIVE SYSTEM(2023) Özdemir, Feride; Taşdemir, Aslı; Çiftçi, Osman; Aydın, Muhterem; Türkmen, Neşe BaşakObjectives: Aroclor (AR) 1254; has many adverse effects on male reproduction such as carcinogenic, teratogenic, immune and endocrine disruption problems. Tetrandrine (TET), a bisbenzillisoquinoline alkaloid isolated from the root of Stephania tetrandra S. Moore, has protective effects such as immunomodulatory, anti-cancer, and anti-inflammatory. The objective of this study was to investigate the possible curative effects of TET therapy against testicular damage (histological, spermatological and oxidative damage) induced by AR1254. Materials and Methods: Twenty-eight male rats were randomly divided into four equal-sized groups: a control group; (1 ml of corn oil by gastric oral gavage), AR1254 group; (2 mg/kg) AR1254 administered intraperitoneally), TET group; (TET by gastric oral gavage 30 mg/kg) and AR 1254 + TET group;(Aroclor 1254 and TET administered together at the same doses as the previous groups. Results: The AR1254 treatment caused morphological and spermatological damage on testis tissue; oedema vacuolization and congestion, in interstitial area, reduction in spermatogenic cells, arrested spermatocytes at different stages of spermatogenesis, shedding of spermatogenic serial cells into tubular lumens, a decline in epididymal sperm concentrations, sperm motility and a rise in abnormal sperm ratios. The AR1254 administration induced an increase in the oxidative parameters and a decrease in enzymatic and nonenzymatic antioxidant levels. The TET treatment significantly ameliorated histological, oxidative, and sperm damage caused by AR1254. Conclusion: This study demonstrated the protective effects of TET against AR1254-induced male rat reproductive damage.Öğe Yeni sentezlenen bir seri 3(2H)-piridazinon türevi bileşiğin beyin ve karaciğer kanser hücre hatlarında sitotoksik etkilerinin araştırılması(2016) Çiftçi, Osman; Özdemir, İlknur; Gökçe, Mehtap; Özdemir, Zeynep; Türkmen, Neşe Başak[Abstract Not Available]
