Araştırmacılar(4)

• Aydın, İsmail Çağrı
• Cetin, Gul
• Dincer, B.
• Karakoy, Zeynep

• ArticleAçık Erişim2026/r/ebyu/10628
  Detorsion is not innocent: pirfenidone prevents contralateral ovarian damage following ovarian torsion

  Halici, Hamza; Karakoy, Zeynep; Yurdgulu, Emir Enis; Ay, Yusuf Anil; Cadirci, Elif; Toktay, Erdem; Kavas, Betul

  Ovarian torsion is a gynecological emergency caused by rotation of the vascular pedicle, leading to ischemia, necrosis, and potential fertility loss. Management remains controversial, particularly regarding oophorectomy versus ovarian preservation. Detorsed ovaries continue cytokine secretion, impairing contralateral ovarian function, and no protective therapy currently exists. This study aimed to compare oophorectomy and detorsion strategies and to determine whether post-detorsion long-term pirfenidone therapy preserves ovarian function, thereby providing experimental resolution to the clinically pivotal “save or sacrifice” dilemma. Forty female rats were divided into five groups: Healthy, IR, IR + OVX, IR + Pirfenidone 50 mg/kg, and IR + Pirfenidone 100 mg/kg. Ischemia was induced in the left ovary of IR groups; in IR + OVX, the ovary was excised at 3 h, while in other groups, ovaries were reperfused. Treatments continued for 30 days. Ovarian tissues and blood were analyzed histopathologically, biochemically, and molecularly. Ovarian ischemia–reperfusion induced a persistent inflammatory and profibrotic response not only in the ischemic ovary but also in the contralateral ovary, leading to reduced estrogen levels and marked histopathological damage. Importantly, detorsion alone did not prevent contralateral injury, whereas oophorectomy attenuated molecular alterations. Post-detorsion pirfenidone therapy dose-dependently restored estrogen production, suppressed inflammasome activation (IL-1β, NLRP3, caspase-1) and fibrotic signaling (SMAD2, SMAD3, TGF-β1), and preserved normal follicular architecture in both ovaries. These findings demonstrate that the detorsed ovary remains a biologically active source of injury and identify pirfenidone as a potential adjunct therapy capable of protecting ovarian function after torsion.

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• ArticleAçık Erişim2026/r/ebyu/10553
  Understanding the relationship between lung GABAA receptors and aquaporin-1: a new therapeutic approach for acute lung injury

  Halici, Hamza; Karakoy, Zeynep; Cadirci, Elif; Halici, Zekai; Ozdemir, Bengul; Toktay, Erdem

  Background: This study aimed to investigate the effects of the GABAA receptor and the potential relationship between GABA/ GABAA receptor signalling and aquaporin-1 in acute lung injury (ALI). Methods: Fifty-six male Wistar albino rats (220–240 g) were divided into seven groups. Two groups received intraperitoneal diazepam at 5 or 10 mg/kg. In two other groups, 0.1 mg/kg flumazenil was administered five minutes after diazepam. Thirty minutes after the final treatment, all groups except the healthy controls were subjected to an LPS- induced ALI model. Lung tissue were collected 24 h after LPS administration and analysed using histopathological, molecular, and biochemical methods. Results: In the present study, it was found that aquaporin-1, which plays an important regulatory role in LPS-damaged lung tissue, decreased and the weight of lung tissue increased in wet/dry analysis of a murine model of ALI. The levels of IL-1β, IL-6, and TNF-α were found to be elevated. Additionally, in groups treated with the GABAA receptor modulator diazepam, the levels of these inflammatory cytokines were significantly reduced and in parallel a significant increase in aquaporin-1 expression was observed. Conclusion: Diazepam, acting as a GABAA receptor modulator, may alleviate ALI by reducing inflammation and enhancing aquaporin-1 expression via GABAA receptor activation.

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• ArticleYalnız künye2026/r/ebyu/10165
  Bioactive properties of Vicia canescens subsp. variegata (Willd.) P.H. Davis, Fabaceae: antioxidant, antiparkinsonian and relevance to food and agriculture use

  Aydın, Bilge; Ertuğrul, Muhammed Sait; Aydın, İsmail Çağrı; Uğan, Rüstem Anıl; Özkaraca, Mustafa; Yuca, Hafize; Özbek, Hilal; Kazaz, Cavit; Okkay, Ufuk; Karakaya, Songül

  BACKGROUND: Various Vicia species belonging to the Fabaceae family are known to be used in different parts of the world both in human nutrition and as animal feed, and also have pharmacological potential in the prevention and treatment of various diseases. With this perspective, in the present study, the possible antiparkinsonian effects of extracts prepared from Vicia canescens subsp. variegata were investigated in cell culture and on 6-hydroxydopamine (6-OHDA)-induced Parkinson's model rats. The effects of the plant on the pathophysiology of Parkinson's disease were evaluated by biochemical and histopathological analyses; in addition, the structures of the compounds isolated from the active extracts were elucidated and the in vitro antioxidant and antiparkinsonian activities of these compounds were determined. RESULTS: Methanol and n-butanol extracts prepared from the aerial parts of V. canescens subsp. variegata showed significant antiparkinsonian effects both in cell culture and in a rat model. Histopathological and biochemical analyses were also parallel to in vivo experiments. As a result of the isolation studies, six flavonol glycosides were obtained from the plant, and their antioxidant capacities as well as antiparkinsonian effects were subsequently evaluated. The highest biological effect was observed in quercetin-3-O-α-l-rhamnopyranoside (quercitrin, VCB-3). CONCLUSION: In the light of the studies, the antiparkinsonian effects of V. canescens subsp. variegata was evaluated. It was seen that they prevented neurodegeneration and the oxidative stress that occurred, and the most effective compounds were determined. Two new compounds named viciacoside A and B have been added to the literature as a result of this research.

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• Review ArticleYalnız künye2025/r/ebyu/12209
  Novel therapeutic approaches targeting 5-HT7 receptors outside the central nervous system

  Kilic, Melis; Karakoy, Zeynep; Halici, Hamza; Cadirci, Elif; Halici, Zekai

  Serotonin (5-HT) is a neurotransmitter found throughout the human body that regulates many physiological events arising from the brain and central nervous system (CNS), such as sleep and appetite. However, it has many other functions in systems outside. In addition to the routine expression of 5-HT7 receptors in CNS regions, such as the pituitary gland, spinal cord, and hippocampus, many studies have reported the expression of these receptors in pathological conditions outside. The role of 5-HT7 receptors outside the CNS has been attracting increased attention in recent years. This review highlights the fact that 5-HT7 receptors are associated with diseases and systems beyond the CNS increasing or decreasing in response to cellular changes. Clinical, basic, in vivo and in vitro studies to date are described, but more research is needed to better understand the role of 5-HT7 receptors outside the CNS.

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• ArticleYayıncıda açık erişim2025/r/ebyu/11967
  Comparative in vitro and in silico evaluation of the toxic effects of metformin and/or ascorbic acid, new treatment options in the treatment of Melasma

  Yalçln, Hülya Tezel; Çaklr, Deniz Arca; Yirün, Anll; Sanajou, Sonia; Işlk, Gözde; Bozdemir, Özlem; Özçelik, Ibrahim; Güdül Bacanll, Merve; Zeybek, Naciye Dilara; Baydar, Terken

  Melasma is a chronic condition that leads to the buildup of melanin pigment in the epidermis and dermis due to active melanocytes. Even though it is considered a non-life-threatening condition, pigment disorders have a negative impact on quality of life. Since melasma treatment is not sufficient and complicated, new treatment options are sought. Research on metformin and ascorbic acid suggested that they might be used against melasma in the scope of "drug repositioning."The MNT-1 human melanoma cell line was used to assess the effects of metformin, ascorbic acid, and metformin+ascorbic acid combination on cytotoxicity and oxidative stress. Melanin, cAMP, L-3,4-dihydroxyphenylalanine (L-DOPA) and tyrosinase levels were determined by commercial ELISA kits and tyrosinase gene expression was analyzed with RT-qPCR. Cytopathological evaluations were performed by phase contrast microscopy. Tyrosinase expression was determined by immunofluorescence (IF) staining of MNT-1 cells. The online service TargetNet was used for biological target screening. The parameters were not significantly altered by ascorbic acid applied at non-cytotoxic concentrations. On the contrary, metformin dramatically raised tyrosinase and intracellular ROS levels. Moreover, intracellular ROS levels and tyrosinase levels were found to be considerably elevated with the combined treatment. Also, potential metformin and ascorbic acid interactions were determined. According to the results, it can be said that these parameters were not significantly altered by ascorbic acid. On the contrary, metformin dramatically raised tyrosinase and intracellular oxidative stress levels. Moreover, intracellular oxidative stress and tyrosinase levels were elevated with the combined treatment. In conclusion, individual treatments of ascorbic acid or metformin may only provide a limited effect when treating melasma and extensive in vitro and in vivo research are required.

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• ArticleYayıncıda açık erişim2025/r/ebyu/11634
  In Vivo Evidence for the Preventive Role of Vaccinium macrocarpon Aiton in Indomethacin-Induced Gastric Ulcer: Focusing on Antioxidant, Anti-Inflammatory and Anti-Apoptotic Mechanisms

  Aydin, Ismail Cagri; Ferah Okkay, Irmak; Okkay, Ufuk; Ozkaraca, Mustafa; Yesilyurt, Fatma; Yilmaz, Aysegul; Cicek, Betul; Karatas, Ozhan; Kalkandelen, Hilal Kadioglu; Aydin, Bilge

  The present study aimed to unveil the gastroprotective potential of Vaccinium macrocarpon (VM) extract and its mechanism of action against indomethacin (INDO)-induced gastric ulcers in rats. To achieve this goal, rats were pretreated with either omeprazole (20 mg/kg) or VM (100 mg/kg) orally for 14 consecutive days. Gastric tissue samples were collected and various parameters were evaluated to understand the mechanism of VM's action, including the levels of superoxide dismutase, malondialdehyde, glutathione, CAT and transforming growth factor beta (TGF-β), as well as the mRNA expression levels of tumour necrosis factor alpha, interleukin 1 beta, nuclear factor kappa B (NF-κB) and inhibitor kappa B (IκB). Additionally, the immunopositivity of cyclooxygenase (COX)-1, COX-2, PGE2, proliferating cell nuclear antigen (PCNA) and caspase-3 was assessed. The total amount of phenolic compounds present in the VM extract was high (58.08 µg/mL gallic acid equivalent/mg extract). The healing effect of VM was demonstrated by an increase in the expression of PCNA. Furthermore, the level of TGF-β was found to increase upon treatment with VM. Analyses of COX-1, COX-2 and PGE2 expression in gastric tissue confirmed the gastroprotective effect of VM. Notably, the expression of NF-κB was markedly reduced, whereas that of IκB was substantially increased. Overall, the findings of this study demonstrate that VM extract has gastroprotective and curative effects against INDO-induced ulcers through its antioxidant, anti-inflammatory, mucosal regenerative and anti-apoptotic activities. Therefore, VM may serve as a useful adjuvant treatment for nonsteroidal anti-inflammatory drugs–induced gastric ulcer disease.

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• ArticleYalnız künye2025/r/ebyu/11433
  Low-dose Bee Venom as a Potential Therapeutic Agent Against Human Chronic Myeloid Leukaemia Cells

  Halici, Hamza; Un, Harun; Celik, Saffet; Karakoy, Zeynep; Bayraktutan, Zafer; Ozlu, Can; Cadirci, Elif; Halici, Zekai; Atila, Alptug; Mercantepe, Filiz

  Bee venom is secreted by a gland in the abdominal cavity of bees. The venom, especially that of honeybees, contains certain enzymes and peptides that, when administered in high doses, are effective against various diseases. Peptides such as melittin and phospholipase A2 can target various cancer cells. In this study, we investigated the antiproliferative effects of administering low-dose bee venom in K-562 chronic myeloid leukaemia cells. Our proteomic study revealed regional variation of the content of bee venom and high levels of melittin, apamin and secapin, as well as phospholipase A2 and hyaluronidase. In addition, eight new, previously unidentified proteins were identified. The effects of bee venom on cell viability and drug–cell interaction were investigated at 24, 48 and 72 h. According to the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) results, the bee venom decreased K-562 cell viability dose-dependently at all time points. Cell viability decreased 48 and 72 h after bee venom administration but increased in the control group left untreated for 72 h. The inhibition percentages for the highest bee venom concentration (0.4 µM) at 24, 48 and 72 h were 55%, 80% and 92%, respectively. The cell–drug interactions indicated that the cell surfaces, which were smooth and clear before drug application, gradually deteriorated and started to shrink after the application. In conclusion, at increasing doses, bee venom was found to have a strong antiproliferative effect in K-562 chronic myeloid leukaemia cell lines.

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• ArticleYalnız künye2025/r/ebyu/11272
  The Effect of Inhaled Ozone Therapy in Two-Hit Rat Model of Lipopolysaccharides-Induced Acute Lung Injury and Bleomycin-Induced Pulmonary Fibrosis

  Celik, Mine; Koca, Mehmet; Halici, Zekai; Tavaci, Taha; Halici, Hamza; Ozkaraca, Mustafa; Karakoy, Zeynep; Bayraktutan, Zafer

  Considering the limited treatment options for acute lung injury (ALI) and pulmonary fibrosis (PF), ozone treatment may be promising as a new immunological agent with its ability to modulate cytokines and interferons. We aimed to investigate the effects of inhaled ozone therapy on both ALI and PF in rat models. A total of 48 albino Wistar male rats were included in the study. Lipopolysaccharide (LPS) was used to induce the ALI model, and bleomycin was used for the PF model. The effects of inhaled ozone (O3) were investigated using the ELISA method. Hematoxylin&eosin staining, Masson’s trichrome staining, and immunohistochemical methods were used for histopathological evaluation. The Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Nuclear Factor kappa B subunit p65 (NF-κB p65) levels in the ALI + 0.08 ppm O3, ALI + 0.12 ppm O3, PF + 0.08 ppm O3, and PF + 0.12 ppm O3 groups statistically decreased to the same extent and approached the levels of control animals. It was observed that IL-1β, IL-6, TNF-α, and NF-κB p65 levels in lung tissues were significantly and dose-dependently decreased compared to the untreated PF and ALI groups, respectively. While fibrosis was severe in the PF + 0.08 ppm O3 group, it decreased to more moderate levels in the PF + 0.12 ppm O3 group. The cytokine levels confirmed that inhaled ozone protected the lungs from both ALI and the development of PF.

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• ArticleYalnız künye2024/r/ebyu/19588
  Galanginin L929 Fare Fibroblast Hücre Hatları Üzerindeki Yara İyileştirme Potansiyelinin İn Vitro Çizik Testi Kullanılarak Değerlendirilmesi

  Aydın, Pelin; Karaköy, Zeynep; Halici, Hamza

  Amaç: Bu çalışmada, anti-enflamatuar ve antioksidan özellikleriyle tanınan bir bileşik olan galanginin, L929 hücre hattında çizik yara iyileşme modeli kullanılarak hücre proliferasyonu ve göçü üzerindeki etkisinin incelenmesi amaçlanmıştır. Yöntemler: Bu çalışmada, farklı galangin konsantrasyonlarının L929 hücre hattında hücre çoğalması ve canlılığı üzerindeki etkilerini MTT yöntemini kullanarak araştırdık. Daha sonra, çizik yara iyileşme testi ile oluşturulan yara hattında farklı galangin konsantrasyonlarının yara kapanması üzerindeki etkilerini inceledik. 0, 12, 24 ve 36. saatlerde yara hattının mikroskobik görüntüleri alındı. Yara kapanma oranları hesaplandı ve yüzde yara kapanma grafiği oluşturuldu. Çalışmamızın sonunda tüm grupların TGF-β seviyeleri ELISA kitleri kullanılarak ölçüldü. Bulgular: L929 hücrelerinde MTT yöntemi ile belirlenen canlılık yüzdelerine göre, galanginin 10, 25 ve 50 μM konsantrasyonları 24, 48 ve 72. saatlerde hücre canlılığını önemli ölçüde artırmıştır. Galanginin bu üç konsantrasyonunun tedavi olarak uygulandığı çizik yara iyileşme modelinde, galanginin 25 ve 50 μM konsantrasyonlarının deney sonunda neredeyse tamamen kapanma gösterdiği gözlemlenmiştir. Ölçülen TGF-β seviyeleri analiz edildiğinde, galangin uygulanan gruplarda kontrol grubuna kıyasla anlamlı bir düşüş gözlenmiştir. Sonuç: İn vitro çizik yara iyileşme modelinde, galangin ile tedavi edilen gruplarda deney sonunda TGF-β seviyelerinde kontrol grubuna kıyasla gözlenen azalma, iyileşme sürecinin neredeyse tamamlandığını ve sitokin salınımında eşzamanlı bir azalmaya neden olduğunu göstermektedir. Bu bulgular, farklı tedavi gruplarında mikroskobik olarak değerlendirilen yüzde kapanma oranlarıyla tutarlıdır.

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• ArticleAçık Erişim2024/r/ebyu/12824
  Targeting Aquaporin-5 by Phosphodiesterase 4 Inhibition Offers New Therapeutic Opportunities for Ovarian Ischemia Reperfusion Injury in Rats

  Bozkurt, Ayse; Karakoy, Zeynep; Aydin, Pelin; Ozdemir, Bengul; Toktay, Erdem; Halici, Zekai; Cadirci, Elif

  This study aimed to examine the effect of Phosphodiesterase 4 (PDE4) inhibition on Aquaporin-5 (AQP5) and its potential cell signaling pathway in the ovarian ischemia reperfusion (OIR) model. Thirty adult female rats were divided into five groups: Group 1; Control: Sham operation, Group 2; OIR that 3 hour ischemia followed by 3 hour reperfusion, Group 3; OIR + Rolipram 1 mg/kg, Group 4; OIR + Rolipram 3 mg/kg, Group 5; OIR + Rolipram 5 mg/kg. Rolipram was administered intraperitoneally to the rats in groups 3-4 and 5 at determined doses 30 minutes before reperfusion. From ovary tissue; Tumor necrosis factor-a (TNF-α), Cyclic adenosine monophosphate (cAMP), Nuclear factor kappa (NF-κB), Interleukin-6 (IL-6), Phosphodiesterase 4D (PDE4D), Mitogen-activated protein kinase (MAPK) and AQP5 levels were measured by ELISA. We also measured the level of AQP5 in ovary tissue by real-time reverse-transcription polymerase chain reaction (RT-PCR). In the OIR groups; TNF-α, NF-κB, IL-6, MAPK inflammatory levels increased, and cAMP and AQP5 levels decreased, which improved with the administration of rolipram doses. Also histopathological results showed damaged ovarian tissue after OIR, while rolipram administration decrased tissue damage in a dose dependent manner. We propose that the protective effect of PDE4 inhibition in OIR may be regulated by AQP5 and its potential cell signaling pathway and may be a new target in OIR therapy. However, clinical studies are needed to appraise these data in humans.

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