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Öğe Anti-inflammatory and anti-apoptotic effects of naringin on bacterial endotoxin-induced small intestine damage in rats(2022) Akin, Ali Tuğrul; El Bechir, Mohamed Lemine; Kaymak, Emin; Ceylan, Tayfun; Sayan, Meryem; Değer, Necla; Karabulut, Derya; Toluk, AyşePurpose: The aim of this study is to investigate the anti inflammatory and anti-apoptotic effects of naringin (NRG), which has many biological properties, on bacterial endotoxin-induced small intestine damage in rats. Materials and Methods: For this purpose, 40 female Wistar albino rats were divided into 4 groups as Control (group given no treatment), LPS (group given 10 mg/kg/i.p lipopolysaccharide), NRG (group given 100 mg/kg/i.p naringin for 14 days) and LPS + NRG (group given 100 mg/kg/i.p naringin for 14 days before 10 mg/kg/i.p lipopolysaccharide injection). After experimental procedure, small intestine tissues of animals were extracted and prepared according to tissue processing protocol. Hematoxylin and Eosin staining were performed to evaluate the histopathological changes and histological damage scoring was applied to compare experimental groups in terms of histopathological changes. Moreover, TNF-? and Caspase-3 expression levels were detected by immunohistochemical staining and the density of immunoreactivity were scored to determine the difference in the expression levels of TNF-? and Caspase-3 expressions among groups. Results: Epithelial and Brunner’s gland damage, mononuclear cell infiltration, hemorrhage, and TNF-? and Caspase-3 expressions significantly increased in the LPS group. However, NRG administrations exerted a strong protective effect on the small intestine tissues in terms of these parameters in LPS+NRG group. Conclusion: This study demonstrated that 100 mg/kg NRG injection can be regarded as a protective agent against negative effects of endotoxin-induced infection on the intestinal mucosa and that it should not be disregarded in further clinical trials.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 Comparison of the Acute and Cumulative Dose Administrations in Doxorubicin-induced Hepatotoxicity via Evaluation of the Histopathological Changes and Inflammation in Rats(Experimental and Applied Medical Science, 2020) Akin, Ali Tuğrul; Kaymak, Emin; Karabulut, Derya; Doğanyiğit, Züleyha; Ceylan, Tayfun; Toluk, Ayşe; Özdamar, SaimDoxorubicin (DOX) may lead to hepatotoxicity when administered chronically or in a high dose. The aim of this study is to determine dose–dependent effects of DOX in rat liver tissue. Thirty male Wistar albino rats were divided into three groups; group I as control, group II as receiving chronically DOX (2 mg/kg, twice in a week, total 20 mg/kg, intraperitoneally) and group III as receiving an acute–single dose of DOX (15 mg/kg, intraperitoneally, on the 20th day) administered groups. At the end of 30th day, animals were sacrificed, and liver tissues were extracted for histopathological and immunohistochemical evaluation. Sections were stained with hematoxylin & eosin to evaluate the histopathological changes and TNF-? and IL-6 expressions were detected by immunohistochemical staining. Both chronic and acute administrations of DOX triggered a significant liver damage. However, it was observed that liver damage induced by acute–single dose DOX administrations were higher than those induced by chronic DOX administrations. TNF-? and IL-6 immunoreactivity was significantly increased in both group II and III group compared to control group. However, immunoreactivity of TNF-? was substantially higher in the group III compared to control. These results demonstrated that acute administrations of DOX relatively induce serious liver damage and inflammatory response.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 thymoquinone on NRF2/NF-kB/MAPK pathway in methotrexate-induced rat testis injury(Iranian Journal of Basic Medical Sciences, 2024) Kaymak, Emin; Ceylan, Tayfun; Akin, Ali Tuğrul; Kuloğlu, Nurhan; Sayan, Meryem; Değer, Necla; Önal, Esra; Yıldırım, Ayşegül Burçin; Karabulut, DeryaObjective(s): In this study, we aimed to investigate the protective effect of Thymoquinone (THQ) against testicular damage caused by Methotrexate (MTX). Materials and Methods: This study consists of 5 groups: Control, Olive oil, THQ, MTX, and MTX+THQ. At the end of the experiment, spermiogram analysis was performed on the rats. In addition, testicular tissues were taken and histopathology, immunohistochemistry, and biochemistry analysis were performed. Biochemical analyses were performed on the serums. Results: According to the results obtained, spermiogram values, Johnson’s testicular biopsy score, SOD, CAT, GPx, FSH, LH, and testosterone values were statistically significantly decreased in the MTX group compared to the control group. In the MTX+THQ group, spermiogram values, Johnson’s testicular biopsy score, SOD, CAT, GPx, FSH, LH, and testosterone values increased statistically significantly compared to the MTX group. NRF2 and HO-1 immunoreactivity were statistically significantly decreased in the MTX group compared to the control group. In the MTX+THQ group, NRF2 and HO-1 immunoreactivity were statistically significantly increased compared to the MTX group. The level of MDA, which is important in lipid damage, and the level of biochemistry results of TNF-?, IL1-?, and IL-6, which are important markers, and the results of p-NF-kB and P38 immunoreactivity were statistically significantly increased in the MTX group compared to the control group. In the MTX+THQ group, these parameters showed a significant decrease compared to the MTX group. Conclusion: According to these results, it is thought that THQ will play a protective role against infertility caused by chemotherapy-induced testicular damage.Öğe 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 Histopathological Changes In Lung Tissue Caused By Diabetes: A Review(DergiPark, 2023) Burçin Yıldırım, Ayşegül; Karabulut, Derya; Kaymak, Emin; Kuloğlu, Nurhan; Akin, Ali Tuğrul; Ceylan, Tayfun; Öztürk, EmelDiabetes mellitus associated with oxidative stress and inflammation can affect many organs. While the effects of diabetes on many organs are well known and documented, its mechanisms of action on the lung are known far less. Hyperglycemia can lead to lung damage by increasing oxidative stresses and inflammation. Diabetes may be a trigger for pulmonary fibrosis, as studies suggest that there may be an important link between pulmonary fibrosis and diabetes. In this review, the histopathological changes caused by diabetes in the lung tissue were summarized. In addition, changes in the lung due to inflammation, oxidative stress and pulmonary fibrosis mechanisms were evaluated.Öğe Investigation of the Effect of Chloroquine on Adriamcycin-Induced Kidney Damage(2022) Kaymak, Emin; Akin, Ali Tuğrul; Ceylan, Tayfun; Karabulut, DeryaAlthough Adriamycin (ADR) is an important anticancer drug used in chemotherapy, it causes nephrotoxicity. The inflammation pathway has an important role in ADR-induced nephrotoxicity. Chloroquine (CLQ), which is used as an antimalarial drug, is used in many diseases. Also, CLQ is known as an anti-inflammatory. In this study, we aimed to investigate the effect of CLQ against nephrotoxicity caused by ADR through the inflammatory pathway. Groups were formed as follows; Control (n = 8), CLQ (n = 8) 50 mg / kg intraperitoneally (i.p.) per day, ADR (n = 8) 2 mg / kg i.p. every 3 days, ADR + CLQ (n = 8) 2mg / kg / i.p. ADR + 50 mg / kg / i.p. CLQ. The experiment took a total of 30 days. At the end of the experiment, kidney tissues were taken from the rats under anesthesia. After fixation in the removed kidney tissues, the tissues were embedded in paraffin by histological methods. Sections were taken from kidney tissues. Renal tissue histopathology and Tumor necrosis factor-alpha (TNF-?) and Nuclear factor-?B p65 (NF-?B p65) immunoreactivities were evaluated. When the kidney tissue was examined, it was seen that damage was caused by ADR. In addition, it was observed that TNF-? and NF-?B p65 immunoreactivities in the kidney significantly increased in the ADR group (p<0.05). Damage and inflammatory markers were found to be decreased in the ADR + CLQ group (p <0.05). Chemotherapeutically administered ADR appears to cause nephrotoxicity. CLQ administered was found to reduce this toxicity. As a result, we showed that the damage caused by ADR-induced nephrotoxicity decreased with the application of CLQ through the TNF-? and NF-?B p65 inflammation pathway.Öğe Investigation of the effect of thymoquinone on kidney damage in isoproterenol-induced myocardial infarction in rats and cardiorenal interactions(Experimental and Applied Medical Science, 2023) Yıldırım, Ayşegül Burçin; Değer, Necla; Sayan, Meryem; Akin, Ali Tuğrul; Ceylan, Tayfun; Kaymak, Emin; Kara, Mehmet; Ünsal, Murat; Karabulut, DeryaThis study aimed to determine whether thymoquinone has any protective effects on renal tissue after an isoproterenol-induced myocardial infarction (MI). Experimental groups were formed as 4 groups (n=8). Control group (C). Thymoquinone group (THQ), 20 mg/kg single dose intragastric (i.g.) daily for seven days. Isoproterenol group (ISO) was administered 100 mg/kg intraperitoneally in two doses on days 7 and 8 of the experiment. Thymoquinone+Isoproterenol group (THQ+ISO), THQ 20 mg/kg i.g. was administered once a day for seven days. In addition, two doses of ISO 100 mg/kg i.p. were administered on the seventh and eighth days. Kidney tissues were evaluated histopathologically. Kidney tissues were evaluated histopathologically. Tumour necrosis factor alpha(TNF-?) and alpha Smooth Muscle Actin(?-SMA) immunoreactivity density changes were determined by immunohistochemistry. Glutathione(GST), Glutathione S-transferases(GSTs) and Interleukin-6(IL-6) levels were evaluated by ELISA method. Isoproterenol injection caused severe histopathological changes on kidney tissue. Also TNF-? and ?-SMA levels were found to be higher in groups where ISO was administered. THQ could be effective on kidney tissue to partially correct these histopathological damages, by decreasing fibrosis and inflammation. This study shows that treatment with THQ is effective in preventing kidney damage caused by ISO-induced MI. We think that THQ as a supplementary food will be effective to prevent kidney damage.Öğe Investigation of the Therapeutic Effects of Chloroquine in Adriamycin-Induced Hepatotoxicity(Sciendo, 2021) Akin, Ali Tuğrul; Kaymak, Emin; Öztürk, Emel; Karabulut, Derya; Kuloğlu, Nurhan; Ceylan, Tayfun; Toluk, AyşeThe aim of this study is to investigate the therapeutic effects of Chloroquine (CLQ) against Adriamycin (ADR) induced hepatotoxicity. ADR is a chemotherapeutic agent used in the treatment of many cancer types, but it causes hepatotoxicity. CLQ is used as an anti-inflammatory drug in the treatment of malaria, rheumatoid arthritis, and pneumonia caused by Covid-19. Rats were divided into four groups: Control group, ADR group (2 mg/kg Adriamycin, one in three days for 30 days, i.p.), CLQ group (50 mg/kg Chloroquine, per day for 30 days, i.p.), ADR+CLQ (2 mg/kg Adriamycin, one in three days for 30 days, i.p. and 50 mg/kg Chloroquine, per day for 30 days, i.p.). Animals were sacrificed, and liver tissues were extracted for further examinations. Histopathological changes in liver tissues were scored and IL-17 immunostaining was performed to determine the expression levels among experimental groups. Bodyweights in the ADR group decreased significantly compared to the Control group and CLQ group. Furthermore, bodyweight in ADR+CLQ group was significantly higher compared to ADR group. The histopathological score was significantly higher in ADR group when compared to Control and CLQ group while CLQ administrations reduced the damage induced by ADR in the ADR+CLQ group. IL-17 immunoreactivity was considerably increased in the ADR group. On the other hand, IL-17 expressions of ADR+CLQ were substantially less compared to ADR group. We suggest that CLQ can be used as a therapeutic agent to reduce the detrimental effects of ADR, thanks to its anti-inflammatory properties.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 The Dose-Dependent Effects Of Doxorubicin In Ratliver Tissue(1st International Ahi Evran Medical and Health Science Congress (IAMHC), 2019) Akin, Ali Tuğrul; Kaymak, Emin; Karabulut, Derya; Doğanyiğit, Züleyha; Ceylan, Tayfun; Toluk, Ayşe; Özdamar, SaimIntroduction: Doxorubicin (DOX) is an anthracycline antibiotic used as an anticancer agent and is a widely used chemotherapeutic for many cancer types such as sarcoma, acute lymphoblastic leukaemia and as well as breast and liver cancers. Recently, it has been shown that DOX causes hepatic toxicity. Toxic effects of DOX are associated with increased formation of reactive oxygen species (ROS), releasing of pro-inflammatory cytokines and induction of apoptotic and necrotic changes in organs. The aim of this study is determine of dose-dependent effects of DOX on inflammation in rat liver tissue. Methods: 30 male rats were assigned to the following groups: Group I as controls, Group II was given Chronic DOX i.p. (2 mg/kg/BW) a total of 10 times, once every three days. Groups III, Acute DOX group which received DOX (15 mg/kg BW) single dose as the intraperitoneal the 20th day of the study. On the 28th day of the experiment, under anesthesia by ether, livers of animals were obtained for histopathological and immunohistochemical evaluation. Sections of 5 ?m thick were sliced with a microtome and stained with hematoxylin and eosin. TNF-alpha and IL-6 were detected immunohistochemically using a polyclonal antibody and the streptavidin–biotin–peroxidase technique. Results: In this study, injection of both DOX Chronic (2mg/kg) and DOX Acute (15 mg/kg) triggered a significant elevation of the liver damage. Hepatic sections of the rats treated with chronic and acute DOX groups were seen intracellular cell degeneration, intracytoplasmic vacuoles, haemorrhage and picnotic cells. IL-6 immunreactivity was significantly increased in chronic group and acute group compared to control group. TNFalpha immunreactivity was significantly increased in chronic group compared to control group. Conclusion: Our results demonstrated that chronically administered doxorubicin increases liver damage. In conclusion, it may be advisable to increase studies on the use of chronic doses in combination of antiinflammatory agents.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.
