Sürdürülebilir Kalkınma Amaçları
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- MakaleAçık Erişim2025Protective Effects of Dexmedetomidine and Amifostine Against Radiotherapy-Induced Kidney Injury
Batcik, Sule; Tumkaya, Levent; Dil, Eyup; Kazancioglu, Leyla; Gaygusuz, Elif; Yazici, Zihni Acar; Ozden, Zulkar; Kilinc, Kagan; Mercantepe, Tolga
Backgrounds: Approximately 18 million individuals were diagnosed with cancer in 2018. The rate is predicted to exceed 22 million by 2030. Radiotherapy is an essential part of cancer therapy, with well documented local and systemic side effects, including oxidative stress and apoptosis. Kidney tissues are also exposed to the deleterious effects of radiotherapy, resulting in acute or chronic kidney function impairment. This study compared the effects of the potent selective α2-adrenoreceptor agonist dexmedetomidine and amifostine on oxidative stress and apoptosis in kidney damage induced by x-irradiation in rats. Methods: Forty Sprague Dawley rats were assigned into five groups: control, x-irradiation, x-irradiation + amifostine, x-irradiation + dexmedetomidine 100 µg/kg, and X-ray irradiation + dexmedetomidine 200 µg/kg. Results: Necrotic tubules and degenerative Bowman’s capsules were present in the x-irradiation group. An increase was determined in malondialdehyde (MDA), Cleaved Caspase-3, and 8-OHdG levels compared to the control group (p ≤ 0.05). In contrast, there was a decrease in necrotic tubules, degenerative Bowman’s capsules, and the levels of MDA, Cleaved Caspase-3, and 8-OHdG in the amifostine and dexmedetomidine 100 µg/kg and 200 µg/kg treatment groups (p ≤ 0.05). Conclusions: Alpha 2 adrenergic receptor agonists exhibit protective effects against kidney injury induced in association with x-irradiation by reducing oxidative stress and apoptosis.
- MakaleYayıncıda açık erişim2025Could Different Doses of Dexmedetomidine Be as Effective as Amifostine Against Radiotherapy-Induced Liver Injury in Rats? Evidence from Mitotic, Apoptotic, Oxidative, and Neurogenic Insights
Beyazal Polat, Hatice; Yilmaz, Hamit; Demir, Kasim; Kilinc, Kagan; Gülhan, Belemir; Rakici, Sema Yilmaz; Tumkaya, Levent
Background/Objectives: Radiotherapy (RT) induces oxidative stress and structural damage in solid tissues, including the liver. This study aimed to investigate the histological and immunohistochemical effects of dexmedetomidine (DEX) and amifostine on their potential protective and regenerative properties against liver injury induced by radiation therapy. Methods: This study consisted of five randomized groups: control, RT, RT-D100, RT-D200, and RT-A (Amifostine). A total of 100 mu g/kg DEX, 200 mu g/kg DEX, and 200 mu g/kg amifostine were administered before radiotherapy as per the experimental design. After RT, liver specimens were analyzed for histological alterations, including periportal and perisinusoidal fibrosis, vacuolization, and pyknotic nuclei. Furthermore, immunohistochemistry investigations were conducted to evaluate apoptosis, mitosis, oxidative stress, and neural regeneration in non-neuronal liver tissue following radiotherapy and subsequent treatment. Results: The control group's liver tissue exhibited standard histological architecture, whereas the RT group displayed severe cellular degeneration, periportal and perisinusoidal fibrosis, cytoplasmic vacuolization, and an increase in pyknotic nuclei. The apoptotic index was markedly reduced in the RT-D100 and RT-D200 groups relative to the RT group. Furthermore, caspase-3 immunoactivity was negligible in the control group, while a significant increase was observed in the RT group. The administration of amifostine significantly increased GAP-43 levels. Conclusions: DEX mitigates RT-induced hepatic injury chiefly through antioxidant and anti-apoptotic pathways, whereas amifostine promotes hepatic regeneration by modulating GAP-43.
- MakaleAçık Erişim2025A Dose-Dependent Study Examining Dexmedetomidine's Possible Effects Against Oxidative, Fibrotic, and Apoptotic Damage Induced by Radiation Exposure in Spleen Tissue
Beyazal Polat, Hatice; Yilmaz, Hamit; Kilinc, Kagan; Gülhan, Belemir; Yilmaz Rakici, Sema; Tümkaya, Levent
Objective: This study aimed to investigate the potential splenic tissue damage induced by radiotherapy (RT) and the potential protective effect of different doses of dexmedetomidine on this damage at the histopathological, immunohistochemical, and biochemical levels. Materials and Methods: In our study, Sprague Dawley rats were randomly divided into four groups: Control, Radiotherapy (RT; 8 Gy), RT + Dexmedetomidine 100 mu g/kg (RT-D100), and RT + Dexmedetomidine 200 mu g/kg (RT-D200). A single dose of 8 Gy radiotherapy was administered to each RT group. Spleen tissues were examined histologically with hematoxylin-eosin and immunohistochemically with anti-Caspase-3, anti-TGF-beta 1, and anti-TGF-beta 3 using light microscopy. TBARS and total thiol levels were also analyzed to assess oxidative stress and antioxidant capacity. Results: Histopathological results showed a significant decrease in white pulp diameter, decreased cellular density, and increased congestion in the red pulp in the RT group. Significant fibrosis, sinusoidal dilatation, vacuolization, and amyloid deposition were detected in the white pulp in the RT group. Regarding anti-caspase-3 immunoreactivity, strong positivity increased in the red pulp in the RT group, while a significant increase was observed in the white pulp in both the RT-D100 and RT groups. While the proportion of TGF-beta 1 immunopositive cells did not change significantly in the RT group, they increased significantly in both dexmedetomidine groups (especially RT-D200). TGF-beta 3 expression increased significantly only in the RT-D100 group. In biochemical analyses, TBARS levels increased significantly in the RT-D100 group. Total thiol levels decreased in the RT group and increased in the dexmedetomidine-treated groups. Conclusions: While RT caused histopathological damage and increased oxidative stress in spleen tissue, dexmedetomidine reduced this damage in a dose-dependent manner. The different immunohistochemical profiles of TGF-beta 1 and TGF-beta 3 suggest that these cytokines may have different functions in the spleen. 100 mu g/kg dexmedetomidine stimulates a regenerative response through TGF-beta 3, while 200 mu g/kg dexmedetomidine may provide immune regulation and antioxidative defense through TGF-beta 1.
- MakaleYalnız künye2020Rosa canina Extract has Antiproliferative and Proapoptotic Effects on Human Lung and Prostate Cancer Cells
Kilinc, Kagan; Demir, Selim; Turan, Ibrahim; Mentese, Ahmet; Orem, Asim; Sonmez, Mehmet; Aliyazicioglu, Yuksel
Although several studies have investigated the cytotoxic effects of different Rosa species, there has been only limited research into the cytotoxic effect of Rosa canina. The purpose of this research was to evaluate the antioxidant properties, phenolic characterization, and cytotoxic effects of R. canina on human lung (A549) and prostate (PC-3) cancer cells and the possible mechanisms involved. The antioxidant properties and phenolic characterization of the extract were determined using spectrophotometric methods and RP-HPLC, respectively. The cytotoxic activity of the extract was determined using the MTT assay. The mechanism involved in the extract’s cytotoxic effect was then evaluated in terms of apoptosis, the cell cycle, mitochondrial membrane potential (MMP), and caspase activity using fluorometric and luminometric methods. The TPC value of the extract was 58.97 ± 2.22 mg gallic acid equivalents per gram sample, and ascorbic acid and p-coumaric acid were detected as major phenolics in the extract. R. canina extract exhibited a selective cytotoxic effect on A549 and PC-3 cells compared to normal fibroblast cells. The extract induced cell cycle arrest at the G1 phase and apoptosis via reduced MMP and increased caspase activity in these cells. Phytomedical applications of R. canina may represent promising approaches in the treatment of cancer.
- MakaleYalnız künye2019Dimethyl Sulfoxide Extract of Dianthus carmelitarum Induces S Phase Arrest and Apoptosis in Human Colon Cancer Cells
Turan, Ibrahim; Demir, Selim; Aliyazicioglu, Rezzan; Kilinc, Kagan; Ozer Yaman, Serap; Akbulut Cakiroglu, Kubra; Kanbolat, Seyda; Ayazoglu Demir, Elif; Mentese, Ahmet; Aliyazicioglu, Yuksel
Although several studies have investigated the cytotoxic effects of different Dianthus species, there has been only limited research into the cytotoxic effect of Dianthus carmelitarum. The purpose of this research was to evaluate the phenolic characterization and the cytotoxic effect of D. carmelitarum on human colon cancer (WiDr) cells and the possible mechanisms involved. Total polyphenolic contents (TPC) and phenolic characterization of the extract were evaluated using the Folin-Cioceltau method and reversed-phase high performance liquid chromatography (RP-HPLC), respectively. The cytotoxic activity of the extract was determined using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. The mechanism involved in the extract’s cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 784.8 ± 40.3 mg gallic acid equivalent per 100 g sample, and sinapic acid and benzoic acid were detected as major phenolics in the extract. D. carmelitarum extract exhibited a selective cytotoxic effect (3.6-fold) on WiDr cells compared to normal colon cells. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in WiDr cells. Phytomedical and nutraceutical applications of D. carmelitarum may represent promising approaches in the treatment of cancer.
- MakaleAçık Erişim2018Cytotoxic effect of Rosa canina extract on human colon cancer cells through repression of telomerase expression
Turan, Ibrahim; Demir, Selim; Kilinc, Kagan; Yaman, Serap Ozer; Misir, Sema; Kara, Hanife; Genc, Berna; Mentese, Ahmet; Aliyazicioglu, Yuksel; Deger, Orhan
Rosa canina is a member of the genus Rosa that has long been used for medical objectives. Several studies have reported cytotoxic effects of different Rosa species, but there has been only limited investigation of the cytotoxic effect of R. canina. The purpose of the current study was to examine the potential effect of R. canina extract on cell viability, the cell cycle, apoptosis, and the expression of telomerase in human colon cancer (WiDr) cells. The cytotoxic effect of the extract was determined using MTT assay. The mechanism involved in the cytotoxic effect of the extract was then evaluated in terms of apoptosis and the cell cycle using flow cytometry. Mitochondrial membrane potential (MMP) was investigated using the fluorometric method, and expression levels of telomerase were studied using RT-PCR. R. canina extract exhibited a selective cytotoxic effect on WiDr cells compared with normal colon cells. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in WiDr cells. R. canina extract significantly repressed telomerase expressions at treatment times of 48 and 72 h in WiDr cells. Our results suggest that R. canina may have considerable potential for development as a novel natural product-based anticancer agent.
- MakaleAçık Erişim2017Antiproliferative and apoptotic effect of Morus nigra extract on human prostate cancer cells
Turan, Ibrahim; Demir, Selim; Kilinc, Kagan; Burnaz, Nesibe Arslan; Yaman, Serap Ozer; Akbulut, Kubra; Mentese, Ahmet; Aliyazicioglu, Yuksel; Deger, Orhan
Background: Morus nigra L. belongs to the family Moraceae and is frequently used in traditional medicine. Numerous studies have investigated the antiproliferative effects of various extracts of different Morus species, but studies involving the in vitro cytotoxic effect of M. nigra extract are very limited. The purpose of this study was to evaluate the phenolic composition and antioxidant activity of dimethyl sulfoxide extract of M. nigra (DEM) and to investigate, for the first time, the probable cytotoxic effect in human prostate adenocarcinoma (PC-3) cells together with the mechanism involved. Methods: Total polyphenolic contents (TPC), ferric reducing antioxidant power (FRAP) and phenolic compounds of DEM were evaluated using spectrophotometric procedures and HPLC. The cytotoxic effect of DEM on PC-3 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic effect of DEM on PC-3 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, while caspase activity was investigated using luminometric analysis. Results: TPC and FRAP values were 20.7 ± 0.3 mg gallic acid equivalents and 48.8 ± 1.6 mg trolox equivalents per g sample, respectively. Ascorbic acid and chlorogenic acid were the major phenolic compounds detected at HPLC analysis. DEM arrested the cell cycle of PC-3 cells at the G1 phase, induced apoptosis via increased caspase activity and reduced mitochondrial membrane potential. Conclusions: Our results indicate that M. nigra may be a novel candidate for the development of new natural product based therapeutic agents against prostate cancer.
- MakaleAçık Erişim2017Morus rubra extract induces G1 cell cycle arrest and apoptosis in human lung and prostate cancer cells
Turan, Ibrahim; Demir, Selim; Kilinc, Kagan; Aliyazicioglu, Yuksel; Alver, Ahmet; Misir, Sema; Yaman, Serap Ozer; Akbulut, Kubra; Mentese, Ahmet; Deger, Orhan
Objective: Cancer is one of the most deadly types of disease and evasion from apoptosis and unstoppable cell proliferation are accepted as its distinctive features. Many studies have evaluated the cytotoxic effect of different Morus species but, there is no study about cytotoxic effect of Morus rubra. In this study we aimed to evaluate phenolic composition, antioxidant properties and cytotoxic effect of acidified dimethyl sulfoxide extract of M. rubra (AMRE). Method: Antioxidant properties, phenolic composition and cytotoxic effect of AMRE were determined using spectrophotometric methods, HPLC, and MTT assay, respectively. Then, mechanisms of cytotoxic effect of AMRE on human prostate (PC-3) and lung (A549) cancer cells were examined in regard to cell cycle, apoptosis and mitochondrial membrane potential using flow cytometric methods. Results: Total phenolic content and reducing power values were 11.9 mg gallic acid equivalents and 42.9 mg trolox equivalents per g sample, respectively. Ascorbic and gallic acid were detected in AMRE as major antioxidant compounds. We determined that AMRE increased cell cycle arrest at G1 phase and exhibited apoptotic features via decreasing mitochondrial membrane potential in both prostate and lung cancer cells. Conclusion: These findings demonstrate that M. rubra extract can affect the behavior of human prostate and lung cancer cells in vitro conditions, and this effect now needs to be investigated in vivo.
- MakaleYalnız künye2017Morus Rubra Extract Induces Cell Cycle Arrest and Apoptosis in Human Colon Cancer Cells Through Endoplasmic Reticulum Stress and Telomerase
Demir, Selim; Turan, Ibrahim; Aliyazicioglu, Yuksel; Kilinc, Kagan; Yaman, Serap Ozer; Ayazoglu Demir, Elif; Arslan, Ayse; Mentese, Ahmet; Deger, Orhan
Many studies have reported cytotoxic effects of different Morus species, but there have been only limited studies on the cytotoxic effect of Morus rubra. The aims of this study were to evaluate the cytotoxic effect of dimethyl sulfoxide extract of M. rubra and to investigate, for the first time, its probable cytotoxic activity in human colon cancer (WiDr) cells, together with the mechanism involved. The cytotoxic activity of extract was determined using MTT assay. The mechanism involved in the cytotoxic effect of extract was then evaluated in terms of apoptosis, and the cell cycle using flow cytometry, mitochondrial membrane potential (MMP) was investigated using the fluorometric method, and expression levels of telomerase and C/EBP homologous protein (CHOP) were investigated using reverse-transcription PCR (RT-PCR). M. rubra extract exhibited moderate selective cytotoxicity on colon cancer cells compared with fibroblast cells. Extract induced cell cycle arrest at the G1 phase and apoptosis via reduced MMP in WiDr cells. Additionally, M. rubra extract significantly repressed telomerase and induced CHOP expressions in WiDr cells. Our results demonstrate that targeting telomerase and endoplasmic reticulum stress represents a promising strategy in colon cancer therapy, and M. rubra may have considerable potential for development as a novel natural product-based anticancer agent.
- MakaleYalnız künye2016Antiproliferative and proapoptotic activity of Turkish propolis on human lung cancer cell line
Demir, Selim; Aliyazicioglu, Yuksel; Turan, Ibrahim; Misir, Sema; Mentese, Ahmet; Yaman, Serap Ozer; Akbulut, Kubra; Kilinc, Kagan; Deger, Orhan
Cancer is a heterogeneous disease, two of whose characteristic features are uncontrollable cell proliferation and insufficient apoptosis. Various studies have investigated the antiproliferative effects of propolis, a natural bee product, from different countries, and its cytotoxic effects have been attributed to its polyphenol contents. The purpose of this study was to show the cytotoxic effects, and possible mechanisms involved, of ethanolic extract of Turkish propolis (EEP) on the human lung cancer (A549) cell line. Cytotoxic activity of EEP on A549 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic action of EEP on A549 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, endoplasmic reticulum stress using RT-PCR, and caspase activity using luminometric analysis. EEP exhibited selective toxicity against A549 cells compared to normal fibroblast cells. We determined that EEP arrested the cell cycle of A549 cells at the G1 phase, induced endoplasmic reticulum stress, caspase activity, and apoptosis and reduced mitochondrial membrane potential. These results indicate that Turkish propolis is capable of reducing cancer cell proliferation and may have a promising role to play in the development of new anticancer drugs in the future.
- MakaleAçık Erişim2015Cytotoxic effect of Turkish propolis on liver, colon, breast, cervix and prostate cancer cell lines
Turan, Ibrahim; Demir, Selim; Misir, Sema; Kilinc, Kagan; Mentese, Ahmet; Aliyazicioglu, Yuksel; Deger, Orhan
Purpose: To investigate the total polyphenolic and flavonoid contents, antioxidant power and cytotoxic activity of ethanol extracts of Turkish propolis (EEP). Methods: The total polyphenolic and flavonoid contents of EEP were determined by spectrometric methods. Antioxidant power and cytotoxic activity of EEP were evaluated using ferric reducing antioxidant power (FRAP) and MTT assays, respectively. Results: The total polyphenolic and flavonoid contents, and FRAP value of EEP were 124.6 ± 1.5 mg gallic acid/g sample dry weight, 42.0 ± 0.8 mg quercetin/g sample dry weight and 311.0 ± 2.5 mg trolox/g sample dry weight, respectively. EEP exhibited powerful cytotoxic effects against the five human cancer cell lines. The highest cytotoxic activity of Turkish EEP was demonstrated on PC-3 cell line (IC50 = 20.7±3.4 μg/mL). Conclusion: The results demonstrate that EEP is a good source of antioxidant and a natural antitumor agent capable of reducing cancer cell proliferation.