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Öğe Chloroquine attenuates chronic hypoxia-induced testicular damage via suppressing endoplasmic reticulum stress and apoptosis in experimental rat model(Wiley Online Library, 2022) Akin, Ali Tuğrul; Kaymak, Emin; Ceylan, Tayfun; Öztürk, Emel; Başaran, Kemal Erdem; Karabulut, Derya; Özdamar, Saim; Yakan, BirkanChronic hypoxia negatively affects male fertility by causing pathological changes in male reproductive system. However, underlying mechanisms of this damage are unknown. Chloroquine (CLQ) is an anti-inflammatory agent that is widely used in the treatment of inflammation-related diseases such as malaria and rheumatoid arthritis. This study aimed to investigate the therapeutic effects of CLQ in the hypoxiainduced testicular damage via assessment of hypoxic response, endoplasmic reticulum stress and apoptosis. For this purpose, 32 Wistar albino rats were divided into 4 groups as control (given 20%-21% O2, no treatment), CLQ (given 50 mg/kg and 20%-21% O2 for 28 days), hypoxia (HX) (given 10% O2 for 28 days) and HX + CLQ (given 50 mg/kg and 10% O2 for 28 days). After the experiment, blood samples and testicular tissues were taken. Histopathological evaluation was performed on testicular tissues and hypoxia-inducible factor 1-? (HIF1-?), heat shock proteins (HSPs) HSP70, HSP90 and growth arrest and DNA damage-inducible gene 153 (GADD153) expression levels were detected via immunohistochemistry. Moreover, apoptotic cells were detected via terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining and serum testosterone levels were determined by enzyme-linked immunosorbent assay (ELISA) assay. Histopathological changes, apoptotic cell numbers and HIF1-?, HSP70, HSP90 and GADD153 expressions significantly increased in HX group (P < .05). Moreover, serum testosterone levels decreased in this group (P > .05). However, CLQ exerted a strong ameliorative effect on all parameters in HX + CLQ group. According to our results, we suggested that CLQ can be considered as an alternative protective agent for eliminating the negative effects of hypoxic conditions on male fertility.Öğe Effect of Chloroquine in Chronic Hypoxia-Induced Bowel Damage(20. Ulusal Anatomi Kongresi, 2019) Kaymak, Emin; Akin, Ali Tuğrul; Yalçın, Betül; Öztürk, Emel; Ceylan, Tayfun; Başaran, Kemal Erdem; Karabulut, Derya; Doğanyiğit, Züleyha; Özdamar, Saim; Yakan, BirkanEffect of chloroquine in chronic hypoxia-induced bowel damageÖğe Effect of vitamin B12 on methotrexate-induced cardiotoxicity in rats(Iranian Journal of Basic Medical Sciences, 2024) Kuloğlu, Nurhan; Karabulut, Derya; Kaymak, Emin; Akin, Ali Tuğrul; Ceylan, Tayfun; Yıldırım, Ayşegül Burçin; Yakan, BirkanObjective(s): Methotrexate (MTX) is a drug with anti-inflammatory and immunosuppressive effects and is also a folic acid antagonist. Our aim in this study is to determine the molecular mechanisms of cardiotoxicity caused by MTX, a chemotherapeutic drug, and to evaluate the protective effects of vitamin B12 on this toxicity. Materials and Methods: A total of 32 rats were used in our study and 4 groups were formed. Control group, Vit B12 group (3 ?g/kg B12 for 15 days, IP), MTX group (20 mg/kg MTX single dose on day 8 of the experiment, IP), MTX +Vit B12 group (3 ?g/kg, IP ), Vit B12 throughout the 15 days, and a single dose of 20 mg/kg MTX (IP) on day 8 of the experiment. Immunohistochemically, expressions of hypoxia-inducible factor 1? (HIF1-?), vascular endothelial growth factor receptor-2 (VEGFR-2), erythropoietin (EPO), and interleukin-6 (IL-6) were evaluated in the heart tissue. Total catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured in the heart tissue. At the same time, ANP and NT-proBNP levels were measured in the blood serum. Results: In the study, the expression of HIF1-? and VEGFR-2 increased significantly in the MTX group, while IL-6 and EPO significantly decreased. At the same time, CAT and SOD levels were significantly decreased and MDA levels increased significantly in the MTX group. While vitamin B12 significantly corrected all these values, it also greatly reduced the increases in ANP and NT-proBNP levels caused by MTX. Conclusion: It is important to use Vit B12 before and after MTX administration to replace the folate that MTX has reduced.Öğe Evaluation Of Epididymitis Tissue Of Cisplatin-Induced Rats(SANAR, 2020) Ceylan, Tayfun; Karabulut, Derya; Öztürk, Emel; Akin, Ali Tuğrul; Kaymak, Emin; Yakan, BirkanAs a chemotherapeutic agent, cisplatin is an antineoplastic agent used in the treatment of various solid tumors such as lung, testicle and bladder cancer (Ezaki, Nishiumi, Azuma, & Yoshida, 2017; Salem, Helmi, & Assaf, 2018). Autophagy abnormality is one of the mechanisms of cell death leading to the development of diseases such as cancer (Yang & Klionsky, 2010). In this study, it was aimed to determine the damage caused by cisplatin on tissue by using autophagy inhibitor and activator. A total of 24 Wistar albino male rats were used in the study, 6 animals in each group. Group I; Control, Group II; Cisplatin (8 mg / kg), Group III; Rapamycin (2 mg / kg), Group IV; Group of 3-methylated (15 mg / kg). While rapamycin and 3-methyladenine were administered for 15 days, cisplatin was applied to these groups on the 7th day of a single experiment. At the end of the experiment, the organs of the rats, which were anesthetized, were removed and placed in formaldehyde for histological follow-up. Hematoxylin-Eosin and Heat-shock protein70 (HSP70) immunohistochemistry was applied to the sections taken after histological techniques. Group I tissue sections had a normal histological appearance. In Group II sections, some areas were disintegrated in the tubular basement membrane and vacuolization was observed in the tubule. In addition, some epithelial cells were observed to be more eosinophilic. Tissue sections of groups III and IV had a more regular appearance as epithelialization, tubule basement membrane. Eosinophilic cells were observed in tubular epithelialization of group IV. HSP70 immunoreactivity was observed in the inter-tubular connective tissue of all groups. HSP70 immunoreactivity was observed in the tubular epithelium of both Group III and Group IV tissue sections, mostly in Group II. Sperm transport, maturation and storage is the most important task of the epididymis (Wang & Kumar, 2012). It was concluded that the organ was affected by agents such as cisplatin to maintain semen quality and potentiality of spermatozoa. We think that HSP70 mediates the formation of autophagy that occurs in the organ.Öğe Histological evaluation of the effects of rapamycin and 3-methyladenine on cisplatin-induced epididymal injury in rats(Cukurova Medical Journal, 2021) Ceylan, Tayfun; Karabulut, Derya; Öztürk, Emel; Akin, Ali Tuğrul; Kaymak, Emin; Yakan, BirkanPurpose: In this study, we aimed to determine the effects of autophagy inhibitor and activator on Cisplatin (Cis)-induced tissue damage. Materials and Methods: A total of 24 male Wistar albino rats were divided into 4 groups including 6 rats per group in this study. Groups are as follows; Control, Cisplatin (Cis) (8 mg/kg), Rapamycin (Rapa) (2 mg/kg), 3-methyladenine (3-MA) (15 mg/kg). Rapa and 3-MA were given intraperitoneally for 15 days. Cis was administered as a single dose on the 7th day of the experimental period. At the end of the experimental procedure, epididymis tissues were extracted. Hematoxylin and eosin staining and Heat shock protein-70 (HSP70) immunohistochemistry were applied to the sections taken after histological techniques. Results: Dispersion in the tubule basement membrane and vacuolization in the tubule was observed in the Cis group. It was also observed that some epithelial cells were more eosinophilic in the Cis group. Tissue sections of Rapa and 3-MA had a more regular appearance in terms of epithelization and tubule basement membrane. HSP70 immunoreactivity was observed in the intertubuler connective tissue of all groups. Conclusion: The epididymis was affected by agents such as Cis in terms of the protection of semen quality and potency of spermatozoa. Rapa may be more effective than 3-MA in the epididymis against Cis toxicity.Öğe Investigation of the Protective Effects of Caffeic Acid Phenethyl Ester against Cisplatin-induced Liver Damage in Rats(2021) Ceylan, Tayfun; Yakan, BirkanCisplatin (CP) is used as an effective chemotherapeutic drug in the treatment of various solid tumors. However, side effects such as hepatotoxicity limit the use of the drug. We investigated the protective effects of caffeic acid phenethyl ester (CAPE), one of the active ingredients of propolis, against hepatotoxicity caused by CP treatment in the liver. 38 Wistar albino rats were divided into 4 groups. Control group was given physiological saline solution for 12 day. CP group was given a single dose of CP (7 mg/kg) on the day 7. CP+CAPE group, was given CAPE (10 ?mol/kg/day) for 12 days and a single dose of CP (7 mg/kg) on day 7. CAPE group received CAPE (10 ?mol/kg/day) for 12 days. Livers of rats sacrificed on the 14th day were stained with hematoxylin-eosin after histological tissue follow-up. The preparations were evaluated and scored. Rat weights were measured and recorded at the beginning and end of the experiment. CP caused significant histopathological changes in the liver. CP also prevented the increase in rat weight. CAPE played an effective role as a protective agent against the histopathological changes caused by CP and showed signs of tissue healing. Our results show that CAPE can be protective against hepatotoxicity associated with CP.Öğe Klorokuin endoplazmik retikulum stresini ve enflamasyonu inhibe ederek sıçanlarda adriamisin uyarılı kardiyotoksisiteyi engeller(Türk Hijyen ve Deneysel Biyoloji Dergisi, 2020) Kaymak, Emin; Akin, Ali Tuğrul; Öztürk, Emel; Ceylan, Tayfun; Kuloğlu, Nurhan; Karabulut, Derya; Yakan, BirkanAmaç: Adriamisin (ADR) kanser türlerinde kullanılan kemoterapötik bir ilaç olarak bilinmektedir. ADR uyarılı kardiyomiyopati toksik özelliğinden dolayı ilacın kullanımını zorlaştırmaktadır. ADR uyarılı kardiyotoksisitede enflamasyon ve endoplazmik retikulum stresi (ERs) artmaktadır. Pek çok kanser türünde kullanılan kemoterapötik ilaç olan ADR’nin yol açtığı kardiyotoksisiteye karşı sıtma ilacı olan klorokuin (CLQ) kullanımının ERs ve enflamasyon üzerinden koruyucu etkilerinin araştırılması amaçlandı. Yöntem: Sıçanlar rastgele 4 gruba ayrıldı: Kontrol grubu (n = 8) dışındakilere, CLQ (n = 8) günde 50 mg/kg intraperitoneal (i.p.), ADR (n = 8) 2 mg/kg i.p. olarak her 3 günde bir, ADR + CLQ grubuna da (n = 8) 2mg/kg i.p. ADR + 50 mg/kg i.p. CLQ uygulandı. Deney toplam 30 gün sürdü. Deneyin sonunda, sıçanlar sakrifiye edildi ve kalp dokuları inceleme için hayvanlardan çıkarıldı. Kalp dokularındaki histopatolojik değişiklikler değerlendirildi ve ERs’yi belirlemek için (Glukoz düzenleyici protein) GRP78 antikoru ve enflamasyon için tümör nekroz faktörü-? (TNF-?) antikoru ile immün boyama yapıldı. Fotoğraflar Olympus BX53 mikroskobu ile çekildi analiz edildi. Bulgular: ADR grubunun kontrol grubuna kıyasla histopatolojik bozulma gösterdiğini ve CLQ tedavisinin ADR tarafından indüklenen bu hasarı iyileştirdiği gözlemlendi. ADR grubunda GRP78 ve TNF-? immünoreaktivitesinde kontrol grubuna göre artış vardı (p<0.0001). ADR + CLQ grubunda GRP78 ve TNF-? immünoreaktivitesinde ADR grubuna göre azalma vardı (p<0.0001). Sonuç: Kronik olarak ADR uygulanan sıçanların kalp dokusunda enflamasyonun ve ERs’nin önemli ölçüde arttığı görülmüştür. Fakat ADR verilen sıçanlarda CLQ uygulamasıyla, ERs ve enflamasyon baskılanmıştır. Bu da tedavi uygulanan gruplarda kalp hasarını önemli ölçüde azaltmıştır.Öğe Kronik Hipoksiye Maruz Bırakılan Ratlardaki Mide Ghrelin Miktarı Üzerine Klorokuin’in Etkisi(2019) Kaymak, Emin; Akin, Ali Tuğrul; Öztürk, Emel; Yalçın, Betül; Ceylan, Tayfun; Başaran, Kemal Erdem; Doğanyiğit, Züleyha; Karabulut, Derya; Özdamar, Saim; Yakan, BirkanGiriş Amaç Yüksek irtifada yaşanan komplikasyonlardan biri olan Anoreksiya, çevresel durumu sinyallerde enerji durumunu belirleyen ve iştahı kontrol eden hipoksinin neden olduğu rahatsızlıklardan kaynaklanmaktadır. Gastrointestinal sistemden salgılanan hormonlar, besin bileşimini algılayarak ve böylece spesifik reseptörler yoluyla hipotalamus tarafından açlığın ve doygunluğun kontrolünü etkileyen endokrin sinyal olarak önemli bir rol oynar (1). 1999'da büyüme hormonu salgı reseptörünün endojen bir ligandı olarak keşfedilen 28 amino asitli bir peptid olan Ghrelin, gastrik mukozanın endokrin hücreleri tarafından sentezlenir (2). Glikoz doyma faktörlerinden biri olduğundan, hipoksi sırasında glikoz homeostazını korumak önemlidir (3). Klorokuin Plasmodium vivax sıtmasında tedavi için kullanıldığı bilinmekte olup aynı zamanda antiinflamatuvar bir maddedir (4,5). Kronik hipoksi ile oluşturulan mide hasarında klorokuin’in ghrelin üzerine etkisini araştırmak amaçlanmıştır. Materyal Metot Bu çalışmada Erciyes Üniversitesi Deneysel ve Klinik Araştırma Merkezinde (DEKAM) yetiştirilen 32 adet 8-12 haftalık, 200-300 gr ağırlığında yetişkin Wistar albino türü erkek sıçanlar kullanılmıştır. Kafesler içinde tutulan sıçanlara günün normal düzeninde 21 0C ve 12 saatlik aydınlık/karanlık ortamında su ve besin ihtiyaçları sağlandı. Gruplar normoksi kontrol n=8, Hipoksi (%10 oksijen/28 gün) kontrol n=8 ve Hipoksi (%10 oksijen/28 gün) + Klorokuin (50mg/kg/28gün) n=8 olarak belirlenmiştir. Deney sonunda denekler tartılıp ağırlıkları kaydedilerek ketamin+ksilazin anestezisi altında mide dokuları çıkarılan hayvanların hayatlarına son verilmiştir. Parafin bloklardan alınan 5-6 ?m kalınlığındaki kesitlere immünohistokimysal olarak ghrelin boyandıktan sonra toplam 50 farklı alanda hücre sayımı yapıldı. İstatistiksel analizler SPSS istatistik yazılımı (SPSS Windows, 24.0 versiyon) kullanıldı. Verilerin normal dağılımı için Kolmogorov–Smirnov testi kullanıldı. Parametrik testlerden One-Way ANOVA ve Post hoc Tukey testi uygulandı. Veriler ortalma ± SD olarak ifade edildi. Analizlerde p<0.05 anlamlı olarak kabul edildi. Bulgular İmmünohistokimyasal değerlendirme sonucu Tablo 1’de gösterilmiştir. Ghrelin pozitif hücre sayısı hipoksi grubunda kontrol grubuna göre istatistiksel olarak anlamlı bir şekilde artış gösterirken, Hipoksi+KLQ grubunda kontrol grubuna yakın sonuç görülmüştür (Şekil 1). Tablo 1: Ghrelin immün pozitif hücre sonuçları. Grup Kontrol Hipoksi Hipoksi+CLQ p Ghrelin 4.18±2.14a 9.80±3.83b 7.74 ±3.02c 0.001 Veriler ortalama±standart sapma olarak ifade edilmiştir. Farklı harf (a,b,c) içeren gruplar arasında anlamlı farklılık vardır. P<0.05 anlamlı kabul edilmiştir. Şekil 1: Ghrelin ile boyanan hücreler A (kontrol), B(hipoksi) ve C (hipoksi+ClQ) gruplarında gösterilmiştir. Görüntü büyütmesi X400. Tartışma ve Sonuç Kronik hipoksinin mide mukozasında ghrelin miktarını önemli bir şekilde artırdığı görülmüştür. Hipoksi ile birlikte klorokuin verilen grupta ise mide ghrelin seviyesinin hipoksiye göre azaldığı görülmüştür. Hipoksi ile besin alımında bir azalma ve kilo kaybı meydana gelmektedir. Bunlara bağlı olarakta hipoksi koşullarında ghrelin seviyesinde artış olmaktadır.Öğe Mitigative effects of chloroquine treatment against hypoxia-induced intestinal injury: a histological and immunohistochemical study(Türk Hijyen ve Deneysel Biyoloji Dergisi, 2022) Akin, Ali Tuğrul; Kaymak, Emin; Öztürk, Emel; Ceylan, Tayfun; Yalçın, Betül; Başaran, Kemal Erdem; Karabulut, Derya; Doğanyiğit, Züleyha; Özdamar, Saim; Yakan, BirkanObjective: Hypoxia has an important role in the disruption of intestinal mucosal integrity because of inflammation and apoptosis induced by inflammatory cytokines such as TNF-? (Tumor necrosis factor-alpha), IL-6 and IFN-y, and apoptotic regulatory proteins. Chloroquine (CLQ) is a drug used in the novel coronavirus disease (COVID-19) and is widely used for the treatment of many inflammatory diseases such as malaria and rheumatoid arthritis. In this study, we aimed to reduce the destructive effects of hypoxia-induced inflammation and apoptosis in the intestinal mucosa of rats with CLQ applications. Methods: For this purpose, a total of 24 Wistar Albino rats were randomly divided into three groups; Group I: Control group (n=8), Group II: Hypoxia (n=8) and Group III: Hypoxia + CLQ (n=8). The control group was housed in plexiglass cages to keep the oxygen levels at 10% levels for 28 days, while the hypoxia and hypoxia+CLQ groups were housed in a normal atmospheric environment (21% O2), and the hypoxia+CLQ group was administered CLQ at a dose of 50 mg/kg every day for 28 days. At the end of the experiment, the intestinal tissues of the experimental animals, were extracted under the anesthesia and they were sacrificed. Results: As a result of histopathological evaluations, it was determined that CLQ applications showed healing properties on the histopathological effects induced by hypoxia in the intestine. While an increase in TNF-? expression was observed in the hypoxia group, a statistically significant decrease was detected in the hypoxia+CLQ group. In addition, Bax expression was found to be statistically significantly lower in the hypoxia+CLQ group when compared to the hypoxia group. On the contrary, it was observed that Bcl-2 expression was statistically significantly increased in the hypoxia+CLQ group compared to the Hypoxia group. Conclusion: We observed that hypoxia causes significant damage to the intestinal mucosa and triggers a severe inflammation that drives cells to apoptosis. Considering the curative effects of chloroquine on the intestinal mucosa, we suggest that this anti-inflammatory drug has a potential to use clinically to alleviate the deleterious effects of hypoxia in the intestine.Öğe Protective effect of melatonin on cisplatin induced acute kidney injury: Role of regulation of heat shock proteins expressions(Indian Journal of Experimental Biology, 2023) Akin, Ali Tuğrul; Ünsal, Murat; Ceylan, Tayfun; Kaymak, Emin; Öztürk, Emel; Kuloğlu, Nurhan; Karabulut, Derya; Yakan, BirkanChemotherapy is one of the major treatment approaches for cancer, and these agents are known to cause severe side effects, including damaging vital organs. Cisplatin (CP) is a commonly used chemotherapeutic agent in the treatment of many cancer types, particularly lung, breast, ovarian, testicular and head-neck cancers. CP is reported to cause damage to damage on brain, kidney, liver and gonads. In this study, is we investigated the protective effects of melatonin (MEL) in acute kidney injury (AKI) induced by CP via assessment of heat-shock protein (HSP) induction in rats. For this purpose, total 40 Wistar albino rats were divided into four groups: Control (n=10), MEL (n=10, 10 mg/kg/i.p. melatonin for 8 days), CP (n=10, 7 mg/kg/i.p. cisplatin at the 5th day), and CP+MEL (n=10, 10 mg/kg/i.p. melatonin for 8 days and 7 mg/kg/i.p. cisplatin at the 5th day). After kidney tissues were extracted, histopathological changes were evaluated and immunoreactivities of HSP47, HSP60, HSP70 and HSP90 in renal cortex were detected via immunohistochemistry. Moreover, blood serum BUN (blood urea nitrogen), creatinine and uric acid levels were measured to assess kidney function. CP group showed histopathological deterioration, and MEL treatment attenuated this damage in CP+MEL group. An increase in HSPs immunoreactivities were detected in renal cortex of CP group when compared with the control and MEL groups, showing increased HSP response because of CP-induced AKI. However, CP-induced HSP induction was significantly lower in the CP+MEL group. Similarly, blood serum BUN, creatinine and uric acid levels were higher in CP group while CP+MEL group showed decreased levels of these parameters. Our results suggest that MEL could exert a significant protective effect against CP-induced AKI via reducing HSP response.Öğe Protective effect of melatonin on cisplatin-induced liver injury in rats(Cukurova Medical Journal, 2022) Kaymak, Emin; Ünsal, Murat; Akin, Ali Tuğrul; Öztürk, Emel; Ceylan, Tayfun; Kuloğlu, Nurhan; Karabulut, Derya; Yakan, BirkanPurpose: We aimed to evaluate the protective effect of melatonin (Mel) on experimental hepatatoxicity induced by cisplatin (Cis). Materials and Methods: A total of 40 Wistar Albino rats were used. Control group (n = 10) daily 0.1 mg / kg isotonic solution (intraperitoneal) i.p. was administered. Cis group (n = 10) was given a single dose of i.p. Cis (7 mg/kg) was administered. Melatonin (Mel) group (n = 10) daily i.p. Mel (10 mg / kg) was administered. Cis + Mel group (n = 10) daily i.p. Mel (10 mg / kg) + single dose i.p. Cis (7mg / kg) was administered. On the 8th day of the experiment, liver tissues of rats were collected histologically and immunohistochemically for tumor necrosis factor-? (TNF-?) analysis. Analyzes were performed for the levels of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), Lactate dehydrogenase (LDH), and albumin for liver function from the serum obtained from the blood. Results: It was observed that liver tissue histopathological score and TNF-? immunoreactivity increased significantly with cisplatin administration compared to the control group. We found that the histopathological score and TNF-? immunoreactivity were decreased in the group treated with melatonin, and the liver function enzymes ALT, AST, and LDH were significantly decreased compared to the cisplatin group. Albumin level, on the other hand, showed a significant improvement in the group treated with melatonin. Conclusion: Melatonin may play a protective role in hepatotoxicity caused by cisplatin by reducing inflammation and preventing the increase in liver enzymes.Öğe Research on Endoplasmic Reticulum Stress-mediated Protective Effect of Melatonin against Cardiotoxicity Following Cisplatin Treatment(Medical Journal of Bakirkoy, 2024) Ceylan, Tayfun; Ünsal, Murat; Kaymak, Emin; Akin, Ali Tuğrul; Kuloğlu, Nurhan; Karabulut, Derya; Yakan, BirkanObjective: Cisplatin (CP) is a chemotherapeutic drug that causes cardiotoxicity. Melatonin (MEL) is secreted by the pineal gland throughout the night. This study aimed to investigate the protective effect of MEL against cardiotoxicity associated with CP exposure. Methods: Physiological saline was applied to Group 1 (control) throughout the experiment. A single dose of CP (7 mg/kg) was administered to Group 2 on the 5th day of the experiment. Group 3 received MEL (10 mg/kg) for 7 days and CP (7 mg/kg) on day 5. MEL (10 mg/kg) was administered to group 4 for 7 days. On the 8th day of the experiment, the hearts were removed under anesthesia. Sections taken from heart tissue samples were stained with hematoxylin and eosin for histopathological evaluation. Additionally, heart tissue sections were immunohistochemically stained for 78-kDa glucose-regulated protein (GRP-78), growth arrest and DNA damage-inducible gene 153 (GADD 153), and connexins (Cx 43) expression. Results: CP application caused cellular damage and disrupted heart tissue tissue integrity. At the same time, CP application caused an increase in the expression of GRP-78 and GADD 153, whereas it caused a decrease in the expression of Cx43. MEL application heals cell damage and impaired tissue integrity. However, while reducing GRP-78 and GADD153 expression; CX had an effect of increasing expression. Conclusion: MEL may have a protective effect against CP-induced cardiotoxicity in rats.Öğe Researches on the protective effect of caffeic acid phenethyl ester on testicular 2 damage caused by cisplatin(2020) Ceylan, Tayfun; Cantürk Tan, Fazile; Kaymak, Emin; Yakan, BirkanBACKGROUND/AIM:Cisplatin (CP), a chemotherapeutic drug, causes damage to spermatogenic serial cells, Sertoli cells and Leydig cells in rat testicles. We aimed to investigate the protective effect of caffeic acid phenethyl ester (CAPE), one of the active ingredients of propolis, in eliminating CP-induced testicular damage. MATERIALS AND METHODS:Group 1 (control group) was given Serum Physiological intraperitoneal (ip) throughout the experiment. Group 2 (CP group) was given a single dose of CP (7 mg / kg) (ip) on the 7th day. Group 3 (CP+CAPE group), CAPE (10 µmol / kg / day) (ip) for 12 days and single dose CP (7 mg / kg) ip on day 7. given as. Group 4 (CAPE group) was given CAPE (10 µmol / kg / day) (ip) for 12 days. On the 14th day of the experiment, the rats were decapitated under xylazine and ketamine anesthesia and their testicles were removed. The sections obtained from the testicles were stained with hematoxylin-eosin and histopathological damage was evaluated. Malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT) enzymatic activities were measured in testicular tissue samples. Testosterone (TES) levels were measured in blood serum. Johnsen testicular biopsy score (JTBS) was used to evaluate testicular tubules. DNA damage was evaluated in sperm samples taken from the ductus epididymis by comet assay technique. RESULTS:In Group 2 given CP, the testicles were severely damaged. It was observed that histological damage was reduced in testes by giving CAPE in Group 3. In addition, according to JTBS, the value was significantly higher in testicular tubules (p < 0.05). Moreover, the MDA level was decreased in the Group 3. But, SOD, CAT and TES levels were increased in the Group 3. DNA damage also decreased significantly in Group 3 compared to Group 2 (p < 0.05). CONCLUSION:As a result, CAPE may be protective against damage caused by CP in the testicles.Öğe Sisplatin’in Oluşturduğu Testis Hasarı Üzerine Kafeik Asit Fenetil Ester’in Koruyucu Etkisinin İncelenmesi(Cell & Tissue Biology Research Turkish, Histology and Embryology Association, 2018) Ceylan, Tayfun; Kaymak, Emin; Yalçın, Betül; Cantürk Tan, Fazile; Yakan, BirkanAmaç: Testisler, erkek üreme hücrelerinin üretilmesi evresi olan spermatogenezin gerçekleştiği ve testosteron başta olmak üzere erkek cinsiyet hormonlarının üretildiği yerlerdir. Antikanserojen bir ilaç olan Sisplatin (SP); sıçan testislerindeki spermatogenik seri hücrelerinde, destek hücreleri olan Sertoli hücrelerinde ve interstisyel alandaki Leydig hücrelerinde hasara yol açmaktadır. Bu hasarın ortadan kaldırılmasında koruyucu etkisiyle propolisin etken maddelerinden biri olan Kafeik Asit Fenetil Ester’in (KAFE) etkisini gözlemlemeyi amaçladık. Gereç ve Yöntemler: Çalışmayla ilgili tüm prosedürler etik kurallara uygun olacak şekilde gerçekleştirildi. Grup 1’e (kontrol grubu) (n=8) deney boyunca diğer gruplara uygulanan KAFE ve SP miktarı kadar izotonik salin solüsyonu intraperitoneal (ip.), Grup 2’ye (n=10) deneyin 7. günü tek doz SP (7 mg/kg) ip. olarak verildi. Grup 3’e (n=10) deneyin başlangıcından itibaren 12 gün boyunca KAFE (10 ?mol/kg/gün) ip. olarak ve aynı gruba 7. günde SP (7 mg/kg) tek doz ip. olarak verildi. Grup 4’e (n=10) ise deneyin başlangıcından itibaren 12 gün boyunca KAFE (10 ?mol/kg/gün) ip. olarak verildi. Sıçanlar deneyin 14. gününde ksilazin ve ketamin anestezisi altında dekapite edildi ve testisleri alındı. Testislerden alınan kesitler hematoksilen ve eozin boyaları ile boyanarak histolojik hasar incelendi. Sıçanlardan elde edilen testis dokusunda Malondialdehit (MDA), Katalaz (KAT) ve Süperoksit Dismutaz (SOD) parametrelerine bakılarak, lipid peroksidasyon ürünü ve antioksidan enzim aktiviteleri tayin edildi. Ayrıca kan serumunda testosteron (TES) parametreleri tayin edildi. Comet Assay tekniğiyle de duktus epididimisten alınan sperm örneklerinde hücre düzeyinde DNA hasarı saptandı ve hasarın miktarı belirlendi. Bulgular: SP uygulanan gruplardan alınan testis dokularında kontrol grubu testis dokularına göre hasar görüldü. Bu hasar spermatogenik seri hücrelerinde artan şekilde bozulma, tubuli seminiferi kontortilerin bazal membranlarında bozulma, interstisyel alandaki Leydig hücrelerinde kısmen hasarlanma ve testis tübülleri içerisinde ödem şeklindeydi. Testis dokusunda bakılan MDA, SOD ve KAT ölçümleri ile kan serum TES ölçümleri de bu hasarlanmaları destekler niteliktedir. Comet Assay bulguları ise spermlerdeki hasarın DNA parçalanmalarından kaynaklı olduğunu gösterdi. Sadece SP uygulaması, sperm DNA parçalanma oranını kontrol grubuna kıyasla önemli ölçüde artırdı (p<0.001). SP ile birlikte KAFE uygulanan gruplardan alınan doku örneklerindeki hasarlar yalnızca SP uygulanan gruplardaki doku ve hücre hasarına göre azalmış olarak gözlendi. Biyokimyasal analizlerde (MDA, SOD, CAT ve TES analizleri) bu bulguları destekler nitelikteydi. Ayrıca Comet Assay tekniği de sperm hücresi DNA’sındaki parçalanmaların azaldığını gösterdi. Sperm DNA parçalanma oranı SP+KAFE grubunda SP grubuna göre anlamlı olarak azaldı (p<0.001). Sonuç: Sonuç olarak tek doz SP uygulanması daha önceki çalışmalarda olduğu gibi sıçan testis dokusunda hasar oluşturmuştur. Çalışmamızda sıçan testis dokusunda oluşan bu hasara karşı KAFE’nin koruyucu etkisi gösterilmiştir.Öğe Sisplatin’in Sıçanlarda Oluşturduğu Böbrek Hasarına Karşı Kafeik Asit Fenetil Ester’in Koruyucu Etkisinin İncelenmesi(ZEUGMA II. ULUSLARARASI MULTİDİSİPLİNER ÇALIŞMALAR KONGRESİ, 2019) Ceylan, Tayfun; Kaymak, Emin; Yakan, BirkanAmaç: Sisplatin(SP), katı tümörlerin tedavisinde yaygın olarak kullanılan anti-kanserojen bir ilaçtır. SP esas olarak böbrekler tarafından atılır ve ana yan etkilerinden biri nefrotoksisitedir (1). Bu yüzden SP?in doza bağımlı olarak oluşturduğu nefrotoksisite ...Öğe The Ameliorative Effects of Caffeic Acid Phenethyl Ester in Cisplatin-Induced Nephrotoxicity: Assessment of the Oxidative Stress an Inflammation(2021) Ceylan, Tayfun; Kaymak, Emin; Akin, Ali Tuğrul; Yakan, BirkanThe aim of this study is to determine the potential therapeutic effects of CAPE in CP-induced nephrotoxicity in rats. Cisplatin (CP) is an antineoplastic chemotherapeutic used for treatment of many cancer types but its applications may induce nephrotoxicity. Caffeic acid phenethyl ester (CAPE) is an active component of propolis and it has several important physiological activities. Rats were divided into four groups: Control, CAPE (10 mmol/kg/i.p), CP (7 mg/kg/i.p), and CP+CAPE (7 mg/kg/i.p, CP and 10 mmol/kg/i.p, CAPE). After administrations, animals were sacrificed, and kidney tissues were extracted. Histopathological changes were evaluated and TNF-a and IL-6 immunostaining were performed. Moreover, tissue SOD, CAT and MDA levels were measured by ELISA assay to assessment of oxidative stress and lipid peroxidation. CP group showed histopathological deterioration compared to the Control group and CAPE treatment attenuated this damage. When compared with Control and CAPE group, an increase in TNF-a and IL-6 immunoreactivities and tissue MDA levels were observed in the CP group while a decrease in tissue SOD and CAT levels were detected. Furthermore, an improvement was observed in the CP+CAPE compared to the CP group. We suggest that CAPE can be used as a therapeutic agent to attenuate the toxic effects of cisplatin, thanks to its antioxidant and anti-inflammatory properties.Öğe Therapeutic effect of thymoquinone on brain damage caused by nonylphenol exposure in rats(Journal of Biochemical and Molecular Toxicology, 2023) Ceylan, Tayfun; Akin, Ali Tuğrul; Karabulut, Derya; Cantürk Tan, Fazile; Taşkıran, Mehmet; Yakan, BirkanNonylphenol (NP), causes various harmful effects such as cognitive impairment and neurotoxicity. Thymoquinone (TQ), has antioxidant, anti-inflammatory, and neuroprotective properties. In this study, our aim is to investigate the effects of TQ on the brain damage caused by NP. Corn oil was applied to the control group. NP (100 mg/kg/day) was administered to the NP and NP + TQ groups for 21 days. TQ (5 mg/kg/day) was administered to the NP + TQ and TQ groups for 7 after 21 days. At the end of the experiment, the new object recognition test was applied to the rats and the rats were killed and their brain tissues were removed. Sections taken from brain tissues were stained with hematoxylin-eosin for histopathological evaluation. In addition, neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), Cas-3, and nerve growth factor (NGF) immunoreactivities were evaluated in brain tissue sections. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) activities were determined. Comet assay was applied to determine DNA damage in cells. The results of our study showed that NP, caused behavioral disorders and damage to the cerebral cortex in rats. This damage in the form of neuron degeneration seen in the cortex was associated with apoptosis involving Cas-3 activation, increased DNA damage, and free oxygen radicals. NP, SOD, and CAT caused a decrease in enzyme activities. In addition, the cellular protein NeuN was decreased, astrocytosis-associated GFAP was increased, and growth factor NGF was decreased. When all our evaluations are taken together, treatment with TQ showed an ameliorative effect on the behavioral impairment and brain damage caused by NP exposure.
