Araştırmacılar(8)

• Abuc, Ozlem Ozgul
• Bal Taştan, Tuğba
• Bal, Tugba
• Demir, Özlem
• Özgül, Ozlem
• YAZICI, GÜLCE NAZ
• Yazlcl, Gülce Naz
• Zırh, Selim

• ArticleYayıncıda açık erişim2026/r/ebyu/19276
  In Vitro Analysis of FSH- and LH-Induced Alterations in Progesterone Levels in Human Granulosa–Theca Cells

  Muftuoglu, Sevda Fatma; Bozdag, Gurkan; Mumusoglu, Sezcan; Portakal, Oytun; Coşkun, Neslihan; Sökmensüer, Lale Karakoç; Güneş, Ali Can; Zirh, Selim

  Objective: This study aimed to evaluate whether administration of luteinizing hormone (LH) before the ovulation trigger could modulate elevated progesterone levels. Methods: Human granulosa-theca tissues were obtained from 15 women aged 18–38 years undergoing laparoscopic ovarian cystectomy at the Department of Gynecology and Obstetrics, Hacettepe University. The tissues were cultured in vitro and treated with 12.5 mIU/mL recombinant follicle-stimulating hormone (r-FSH; Group A), 18.75 mIU/mL r-FSH (Group B), or 18.75 mIU/mL r-FSH plus 6.25 mIU/mL recombinant LH (r- LH; Group C). Baseline and post-treatment estradiol (E2) and progesterone concentrations were measured at 0, 24, and 48 hours. Immunofluorescence staining for aromatase, cytochrome P450, and Ki67 was performed to assess steroidogenic activity and cellular proliferation. Results: A mild trend toward reduced progesterone and increased E2 levels was observed following LH supplementation at both time points; however, these changes did not reach statistically significant. No statistically significante differences were observed in progesterone or E2 levels among the treatment groups at 24 h (P=0.891 and P=0.805, respectively) or 48 h (P=0.878 and P=0.505, respectively). Expression levels of aromatase, cytochrome P450, and Ki67 did not differ significantly between groups at 24 h (P=0.665, P=0.932 and P=0.953, respectively) or 48 h (P=0.911, P=0.674 and P=0.202, respectively). Conclusion: These findings suggest that although r-LH addition to high-dose r-FSH does not significantly alter progesterone synthesis, it may exert a subtle regulatory effect on steroidogenesis. Larger studies with extended culture durations are needed to further elucidate the biological and clinical significance of these observations.

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• ArticleYayıncıda açık erişim2026/r/ebyu/11523
  Neuroendocrine effects of exogenous adropin administration on the hypothalamic pituitary testicular axis in male rats

  Eraslan, Ersen; Tanyeli, Ayhan; Güler, Mustafa Can; Özbek Bilgin, Aslı; Ekinci Akdemir, Fazile Nur; Polat, Elif; Çomakli, Selim; Kurt, Nezahat; Bal Taştan, Tuğba

  Background/aim: Obesity impairs male fertility through metabolic dysfunction, oxidative stress, and disruption of the hypothalamic– pituitary–testicular (HPT) axis. Adropin (ADR), a peptide hormone whose circulating levels are reduced in obesity, plays emerging roles in metabolic homeostasis; however, its involvement in reproductive endocrine regulation remains unclear. The present study was conducted in healthy, nonobese male rats and aimed to investigate the neuroendocrine and testicular effects of exogenous ADR administration, focusing on circulating reproductive hormones, hypothalamic regulatory peptides, and testicular antioxidant pathways. Materials and methods: Thirty-two male Wistar rats were randomized into control, sham, low-dose ADR (4 μg/kg/day), and high-dose ADR (40 μg/kg/day) groups and treated for 10 days. An enzyme-linked immunosorbent assay (ELISA) was used to measure circulating gonadotropins, testosterone, inhibin B, and activin A. Hypothalamic gonadotropin-releasing hormone (GnRH) and kisspeptin expression, and testicular superoxide dismutase 1 (SOD1) localization were assessed by immunohistochemistry. Brain and testis morphology were examined histologically. Results: High-dose ADR administration was associated with increased hypothalamic GnRH and kisspeptin expression, accompanied by reduced circulating LH levels, while FSH concentrations remained unchanged. Testosterone and inhibin B levels were higher, whereas activin A levels were lower, in the high-dose ADR group compared with controls. ADR administration was also associated with enhanced testicular SOD1 immunoreactivity and dose-dependent reductions in body weight. No overt histopathological alterations were observed in the cerebral cortex or testicular tissue. Conclusion: In healthy, nonobese male rats, exogenous ADR administration was associated with changes in central neuroendocrine markers and testicular antioxidant responses without overt histopathological alterations. These findings do not demonstrate improvements in fertility but suggest that ADR may be involved in pathways linking metabolic signals with reproductive endocrine regulation. The potential relevance of these observations to obesity-associated male reproductive dysfunction remains hypothesis-generating and requires confirmation in appropriate disease models and functional reproductive studies.

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• ArticleAçık Erişim2026/r/ebyu/11360
  Potential Hepatoprotective Effects of Adenosine Triphosphate Against Olaparib-Induced Oxidative Liver Injury: An Experimental Rat Model

  Baykan, Ahmed Ramiz; Cerrah, Serkan; Kartal Baykan, Emine; Tanas, Serdar; Yavuzer, Bulent; Yazici, Gulce Naz; Kuzucu, Mehmet; Altuner, Durdu; Suleyman, Halis

  Background: Olaparib, a clinically established poly (ADP-ribose) polymerase (PARP) inhibitor widely used in oncology, has significantly improved outcomes in several malignancies. However, increasing evidence indicates that olaparib may induce hepatocellular injury through mechanisms involving oxidative stress, inflammation, and mitochondrial dysfunction. Adenosine triphosphate (ATP), a key regulator of cellular bioenergetics and redox homeostasis, may confer protection against oxidative tissue injury. This study investigated the hepatoprotective effects of ATP against olaparib-induced oxidative liver damage in rats and compared its efficacy with melatonin. Methods: Twenty-four male albino Wistar rats were randomly assigned to four experimental groups (n = 6): healthy control (HG), olaparib-treated (OLP), ATP plus olaparib (ATOL), and melatonin plus olaparib (MLOL). Olaparib was administered at a dose of 100 mg/kg orally twice daily, whereas ATP (5 mg/kg, intraperitoneally) and melatonin (10 mg/kg, orally) were administered once daily. The treatments were administered for 14 consecutive days. Hepatic oxidative and inflammatory status was assessed by measuring malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), interleukin-6 (IL-6) and ATP levels in liver tissue. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured as biochemical indicators of hepatocellular injury. Liver tissues were also examined histopathologically. Results: Olaparib administration significantly increased hepatic MDA and IL-6 levels together with serum ALT and AST activities, while significantly reducing hepatic tGSH and ATP levels and SOD and CAT activities compared with the healthy group (p < 0.001). Both ATP and melatonin significantly attenuated these alterations (p < 0.001). Notably, ATP demonstrated a more pronounced protective effect than melatonin, particularly in suppressing aminotransferase elevations and improving histopathological liver architecture. Conclusion: ATP significantly alleviates olaparib-induced hepatotoxicity by attenuating oxidative stress, suppressing inflammatory responses, restoring antioxidant defense mechanisms and significantly replenishing depleted hepatic ATP levels. These findings suggest that ATP may represent a promising therapeutic strategy for preventing PARP inhibitor-associated drug-induced liver injury.

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• ArticleAçık Erişim2026/r/ebyu/11251
  Pathophysiology of sildenafil-induced ocular toxicity in rats and treatment

  Cicek, Ibrahim; Caliskan, Busra; Yavuzer, Bulent; Altuner, Durdu; Tastan, Tugba Bal; Coban, Taha Abdulkadir; Karatas, Ezgi; Suleyman, Halis

  RESULTS: Sildenafil increased oxidant (malondialdehyde) levels and decreased antioxidant levels (total glutathione, superoxide dismutase, catalase) in rat ocular tissues and caused severe oxidative stress. In addition, sildenafil has been shown histopathologically to cause oxidative damage in retinal layers. ATP treatment suppressed oxidative stress and attenuated histopathological damage in the retinal layers. CONCLUSION: ATP protects retinal tissue against sildenafil-induced ocular oxidative damage in rats and may contribute to the development of novel approaches to prevent or treat this damage.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10955
  18β-Glycyrrhetinic acid-loaded silver nanoparticles mitigate neuroinflammation and endoplasmic reticulum stress in the brain tissue of diabetic rats

  Parlak, Seçil Nazife; Yakut, Seda; Kara, Adem; Demir, Özlem; Şebin, Saime Özbek

  Objective(s): Diabetes mellitus (DM) causes oxidative stress, neuroinflammation, and endoplasmic reticulum (ER) dysfunction that contribute to neurodegeneration. This study investigated the effects of 18β-glycyrrhetinic acid-loaded silver nanoparticles (18β-GA-AgNPs) on brain injury in diabetic rats. Materials and Methods: Fifty-six male Wistar rats were divided into eight groups: Sham, 18β-GA, AgNPs, 18β-GA-AgNPs, DM, DM+18β-GA, DM+AgNPs, and DM+18β-GA-AgNPs. Diabetes was induced by alloxan (120 mg/kg, IP), and treatments were administered orally for 14 days. Biochemical markers (MDA, GSH, SOD), histopathology, and expression of ER stress and apoptotic proteins (ATF6, IRE1, Caspase-3, BCL-2, CREB, TNF-α, and IL-1β) were evaluated. Results: The DM group exhibited significant increases in MDA, TNF-α, IL-1β, ATF6, and Caspase-3 with reduced GSH, SOD, and BCL-2, indicating oxidative stress, inflammation, apoptosis, and ER stress. In contrast, IRE1 levels remained unchanged in DM rats but showed a slight elevation in the AgNPs group. Treatment with 18β-GA-AgNPs markedly reduced MDA, TNF-α, IL-1β, ATF6, and Caspase-3, while restoring GSH, SOD, BCL-2, and CREB expression. Histopathological analysis confirmed neuronal apoptosis and perivascular and extracellular space enlargement in DM rats, whereas 18β-GA-AgNPs substantially attenuated these changes. Overall, 18β-GA-AgNPs provided synergistic neuroprotection by suppressing oxidative stress, inflammation, and ER stress while enhancing antioxidant and anti-apoptotic defenses. Conclusion: These findings suggest that 18β-GA-AgNPs may represent a promising therapeutic strategy against diabetes-associated neurodegeneration, although further long-term, ultrastructural, and sex-inclusive studies are warranted.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10856
  Protective Role of Adenosine Triphosphate Against Tamoxifen-Induced Retinal Toxicity in a Rat Model

  Karatas, Ezgi; Yavuzer, Bulent; Koksaldi, Seher; Kayabasi, Mustafa; Sezgin, Esra Tuba; Sarigul, Cengiz; Demir, Ozlem; Suleyman, Bahadir; Suleyman, Halis

  Background and Objectives: Tamoxifen, a cornerstone selective estrogen receptor modulator in breast cancer therapy, is increasingly recognized to be associated with retinal toxicity characterized by mitochondrial dysfunction, oxidative stress, lipid peroxidation, and oxidative DNA injury. By targeting mitochondrial bioenergetic dysfunction and redox disequilibrium, adenosine triphosphate (ATP) emerges as a biologically plausible candidate for retinal cytoprotection. This study aimed to evaluate the protective effect of ATP against tamoxifen-induced retinal toxicity in a rat model. Materials and Methods: Twenty-four male albino Wistar rats were randomly assigned to four groups: healthy control (HG), ATP-alone (ATPG, 4 mg/kg, intraperitoneally), tamoxifen-alone (TAMG, 5 mg/kg, orally), and tamoxifen plus ATP-treated (ATAG; ATP, 4 mg/kg, intraperitoneally; tamoxifen, 5 mg/kg, orally). Treatments were administered once daily for 30 days. Oxidative stress markers (malondialdehyde, total glutathione), antioxidant enzyme activities (superoxide dismutase, catalase), and oxidative DNA damage (8-hydroxy-2′-deoxyguanosine) were assessed in ocular tissues. Retinal histopathological evaluation included hematoxylin–eosin staining with semiquantitative assessment of edema, vascular congestion, polymorphonuclear leukocyte infiltration, and cytoplasmic vacuolization, together with quantitative measurements of retinal layer thicknesses and ganglion cell layer (GCL) cell counts. Results: Tamoxifen administration induced marked oxidative stress, antioxidant depletion, and increased oxidative DNA damage in ocular tissues, accompanied by significant thickening of retinal layers, reduced GCL cell counts, and pronounced disruption of retinal architecture. By comparison, ATP co-administration significantly suppressed lipid peroxidation and restored antioxidant defenses, thereby reducing oxidative DNA damage and preserving retinal structural integrity, as reflected by partial normalization of retinal layer thicknesses, preservation of GCL cell counts, and the presence of only mild residual edema. Conclusions: These findings indicate that ATP attenuates tamoxifen-induced retinal toxicity by supporting mitochondrial energy balance and redox homeostasis. Accordingly, ATP administration may represent a promising protective approach for reducing retinal injury associated with long-term tamoxifen therapy.

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• ArticleYalnız künye2026/r/ebyu/10832
  Astaxanthin and omega-3 fatty acids enhance endometrial receptivity in a rat model of polycystic ovary syndrome

  Bal Taştan, Tuğba; Selli, Jale; Toktay, Erdem; Üstündağ, Hilal; Ugan, Rüstem Anıl

  Polycystic ovary syndrome (PCOS) adversely affects endometrial receptivity and fertility outcomes. This study investigated whether combining high-dose antioxidants (astaxanthin or omega-3 fatty acids) with metformin improves endometrial receptivity markers, reduces oxidative stress, and normalizes hormone profiles in a PCOS rat model compared to metformin alone or no treatment. Fifty-six female Sprague–Dawley rats (200-250g) were divided into seven groups: Control, PCOS, PCOS + Met, and groups receiving metformin plus either astaxanthin (PCOS + Met + AX5 or PCOS + Met + AX10) or omega-3 (PCOS + Met + OMG400 or PCOS + Met + OMG1000). PCOS was induced using letrozole for 21 days, followed by one week of treatment. After establishing endometrial receptivity, uterine tissues were analyzed histopathologically, immunohistochemically, and biochemically on day 5. The PCOS group demonstrated significant increases in body weight and oxidative stress markers (malondialdehyde) compared to controls (p < 0.001). High-dose antioxidant supplementation (PCOS + Met + AX10 and PCOS + Met + OMG1000) significantly improved these parameters (p < 0.001). Immunohistochemically, integrin β3 expression increased while mucin 1 (MUC-1) decreased in high-dose groups compared to PCOS (p < 0.001). The LH:FSH ratio normalized to control levels in PCOS + Met + AX10 and PCOS + Met + OMG1000 groups. Histological examination revealed enhanced endometrial morphology and increased pinopode-like structure formation in antioxidant-supplemented groups. High-dose astaxanthin and omega-3 fatty acid supplementation, combined with metformin, may enhance endometrial receptivity in PCOS by reducing oxidative stress and modulating key implantation markers. This therapeutic approach could potentially improve fertility outcomes in women with PCOS.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10775
  Protective Effects of Adenosine Triphosphate and Flunarizine on Erlotinib-Induced Ovarian Damage: An Experimental Study

  Yavuz, Arzu; Uzel, Kemine; Sezgin, Esra Tuba; Kuzucu, Mehmet; Yılmaz, Nesrin; Yazici, Gülcenaz; Hendem, Engin; Süleyman, Halis

  (1) Background: Erlotinib is a tyrosine kinase inhibitor (TKI) widely used in cancer therapy; however, its potential adverse effects on ovarian tissue have not been fully elucidated. The present study aimed to investigate erlotinib-induced ovarian injury and to evaluate the protective effects of adenosine triphosphate (ATP) and flunarizine, administered alone or in combination, using biochemical and histopathological analyses in a rat model. (2) Methods: Thirty female rats were randomly allocated into five groups (n = 6 per group): healthy control, erlotinib, ATP + erlotinib, flunarizine + erlotinib, and ATP + flunarizine + erlotinib. ATP (5 mg/kg, intraperitoneal) and flunarizine (5 mg/kg, oral gavage) were administered daily for two weeks, while erlotinib (5 mg/kg) was given orally every two days for two weeks. Ovarian tissues were collected for oxidative stress analysis and histopathological evaluation, and blood samples were obtained for the measurement of serum prolactin and AMH levels. (3) Results: Erlotinib administration resulted in significant oxidative stress and histopathological alterations in ovarian tissue, accompanied by a reduction in serum AMH levels, while prolactin levels remained unchanged. Treatment with ATP or flunarizine partially attenuated these alterations. (4) Conclusions: Combined ATP and flunarizine administration showed stronger protective effects, improving biochemical parameters and preserving ovarian histology, suggesting a protective role against erlotinib-induced ovarian injury.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10534
  Comparative Protective Effects of Anakinra and Tocilizumab in Experimental Ocular Ischemic Syndrome

  Karimov, Shavkatbek; Sezgin, Esra Tuba; Mammadov, Renad; Suleyman, Bahadir; Yaqudov, Kamandar; Yazici, Gulce Naz; Coban, Taha Abdulkadir; Suleyman, Halis; Bayrakceken, Kemal

  Ocular ischemic syndrome (OIS) is a vision-threatening disorder characterized by retinal ischemia, oxidative stress, and inflammation. In this study, the protective effects of anakinra, an interleukin-1 receptor antagonist, were investigated and compared with those of tocilizumab, an interleukin-6 receptor antagonist. Twenty-four male Wistar rats were randomly assigned to four groups (n = 6 per group): sham-operated (SG), carotid artery clamping/unclamping (CUG), anakinra-treated carotid artery clamping/unclamping (ACUG), and tocilizumab-treated carotid artery clamping/unclamping (TCUG). An experimental ocular ischemic injury model induced by transient bilateral common carotid artery occlusion was established by transient bilateral common carotid artery clamping followed by reperfusion. Retinal tissues were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) levels, and histopathological examinations were performed. OIS markedly increased MDA, TNF-α, IL-1β, and IL-6 levels while significantly decreasing tGSH, SOD, and CAT activities. Both anakinra and tocilizumab attenuated oxidative stress and inflammatory responses; however, anakinra produced notably greater improvements in MDA, tGSH, SOD, and CAT levels. Histopathological evaluation demonstrated that both treatments reduced retinal injury, edema, vascular congestion, and inflammatory cell infiltration. Although retinal architecture appeared slightly better preserved in the anakinra-treated group, histopathological scores were comparable between the treatment groups. These findings suggest that anakinra may attenuate oxidative and inflammatory retinal damage in this experimental ocular ischemic injury model and may provide greater biochemical protection than tocilizumab, whereas histopathological protection was comparable between treatments. Nevertheless, further experimental and clinical studies are required to confirm these findings.

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• ArticleAçık Erişim2026/r/ebyu/10432
  Flunarizine attenuates ischemia–reperfusion–induced ovarian injury in rats

  Yavuz, Arzu; Uzel, Kemine; Sezgin, Esra Tuba; Paltacı, Şeyma İlayda; Demir, Özlem; Kuzucu, Mehmet; Süleyman, Halis

  Background: Ovarian ischemia–reperfusion (I/R) injury is associated with oxidative stress, inflammation, and histopathological damage. The aim of this study was to investigate the potential protective effects of flunarizine against ovarian I/R–induced injury in an experimental rat model. Methods: Rats were divided into four groups: healthy control (HG), sham-operated (SOG), ovarian ischemia–reperfusion (OIR), and flunarizine-treated OIR (FOIR). Ovarian tissues were analyzed in terms of oxidative stress markers, antioxidant enzyme activities, inflammatory cytokines, and histopathological alterations, including follicle counting. Results: Ovarian I/R significantly increased tissue levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) while significantly decreasing total glutathione (tGSH), superoxide dismutase (SOD) and catalase (CAT) levels. Histopathological evaluation revealed severe follicular degeneration, interstitial edema, vascular congestion, and inflammatory cell infiltration in the OIR group. Following flunarizine administration, these biochemical and histopathological alterations were significantly ameliorated, and a partial restoration in follicle counts was observed. Conclusion: The findings of this study demonstrate that flunarizine exerts protective effects against ovarian I/R injury by reducing oxidative stress, inflammation, and histopathological damage.

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