Araştırmacılar(18)

• Alp, Nurdan Alcan
• Alpcan, Hilal
• Altuner, Durdu
• Ates, Irem
• Barun, Sureyya
• Bayrak, Oguzhan
• Bilgin, Asli Ozbek
• Bulut, Seval
• Cerrah, Serkan
• Cetin, Nihal
• Hacimuftuoglu, Fazil
• Halis, Suleyman
• Kaya, Tuğba
• Mamedov, Renad
• Mammadov, Renad
• Suleyman, Bahadir
• Suleyman, Halis
• Yavuzer, Bulent

• ArticleAçık Erişim2026/r/ebyu/18730
  ATP attenuates olaparib-induced gastric damage in rats

  Fakirullahoglu, Mesud; Temiz, Ayetullah; Yeni, Mustafa; Sezgin, Esra Tuba; Yazici, Gulce Naz; Altuner, Durdu; Gulaboglu, Mine; Suleyman, Halis

  Background Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor widely used in cancer therapy, has been associated with gastrointestinal adverse effects; however, the underlying mechanisms remain unclear. Previous studies have suggested that oxidative stress may contribute to olaparib-induced tissue injury.Objective This study aimed to investigate the protective effects of adenosine triphosphate (ATP) against olaparib-induced gastric damage in rats.Methods Animals were divided into healthy control (HG), olaparib alone (OLPG), ATP alone (ATPG), and ATP + olaparib (ATOLG) groups. Gastric injury was evaluated by macroscopic assessment of ulcer area and ulcer number. Histopathological alterations were examined using hematoxylin-eosin (H&E) staining, and oxidative stress status was assessed by measuring lipid peroxidation and antioxidant defense parameters.Results Olaparib administration induced marked gastric mucosal injury, characterized by increased ulcer area and ulcer number, severe histopathological damage, and pronounced oxidative stress. In contrast, ATP co-administration significantly attenuated gastric injury, as evidenced by reduced ulcer area and ulcer number, improved histopathological architecture, and restoration of oxidative balance. Compared with the OLPG group, the ATOLG group showed significant improvement in macroscopic, histopathological, and oxidative stress parameters.Conclusion ATP administration attenuated olaparib-induced gastric damage and improved oxidative stress parameters in rats. Although the underlying mechanisms were not directly investigated in the present study, the obtained findings provide preliminary experimental evidence suggesting that ATP may have protective potential against olaparib-induced gastric injury.

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• Review ArticleAçık Erişim2026/r/ebyu/19221
  Pharmacological Modulation of Mitochondrial Dysfunction in Experimental Models of Hepatic Injury

  Bilgin, Aslı Özbek

  Mitochondrial dysfunction plays a central role in the pathogenesis of various liver diseases, ranging from drug-induced liver damage to steatotic liver disease associated with metabolic dysfunction. This review synthesizes recent advances in pharmacological strategies targeting mitochondrial quality control mechanisms. The shift from non-specific antioxidants to mitochondria-targeted agents is highlighted, as are the emerging roles of cardiolipin stabilizers (SS-31), next-generation cyclophilin inhibitors (Rencofilstat, C105SR), and modulation of immunometabolic pathways such as cGAS-STING and NLRP3. The transition of these promising experimental agents to clinical applications is also presented.

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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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• ArticleYayıncıda açık erişim2026/r/ebyu/11349
  Protective effects of adenosine triphosphate, thiamin, thiamin pyrophosphate, and their combination against linezolid-induced renal injury and lactic acidosis in rats

  Admis, Ozlem; Yavuzer, Bulent; Mammadov, Renad; Suleyman, Bahadir; Altuner, Durdu; Mendil, Ali Sefa; Yucel, Nurinisa; Suleyman, Halis

  Linezolid, an oxazolidinone antibiotic effective against Gram-positive pathogens, may cause nephrotoxicity and lactic acidosis during prolonged therapy. This experimental study investigated the protective effects of adenosine triphosphate (ATP), thiamin, thiamin pyrophosphate (TPP), and their combination (ATTP) on linezolid-induced renal injury and lactic acidosis in rats. Thirty-six male Wistar rats were randomly divided into six groups (n = 6): healthy control (HG), linezolid only (LZD), ATP+linezolid (ATLZD), thiamin + linezolid (TLZD), TPP+linezolid (TPLZD), and ATP+thiamin + TPP+linezolid (ATTPL). Linezolid (125 mg/kg, orally) was administered twice daily, while ATP (4 mg/kg), thiamin (20 mg/kg), and TPP (20 mg/kg) were given intraperitoneally once daily for 28 days. At the end of treatment, kidney tissues were examined for oxidative stress markers [malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT)] and histopathology, and blood samples were analyzed for blood urea nitrogen (BUN), creatinine, and lactate. Linezolid increased oxidative stress, suppressed antioxidants, and elevated BUN, creatinine, and lactate levels. ATP partially improved the oxidative balance in renal tissue but failed to prevent hyperlactatemia and impaired renal function. Thiamin did not produce significant changes. TPP markedly improved oxidative stress markers and reduced renal dysfunction. The triple combination provided the most pronounced protection, restoring antioxidant defenses, kidney function, and lactate levels to near-control values. Histopathological evaluation revealed marked tubular degeneration, interstitial hemorrhage, and mononuclear cell infiltration in the linezolid group, which were markedly improved by TPP and combination therapy. These findings indicate that TPP protects against linezolid-induced nephrotoxicity and lactic acidosis, with its efficacy further enhanced by ATP.

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• ArticleAçık Erişim2026/r/ebyu/11274
  Effects of adenosine triphosphate and reduced glutathione on biochemical, histopathological and immunofluorescence alterations associated with atezolizumab-induced cardiac tissue injury

  Yasar, Yesim Kaya; Sezgin, Esra Tuba; Suleyman, Bahadir; Mammadov, Renad; Ozkaraca, Mustafa; Gungor, Ali; Coban, Taha Abdulkadir; Suleyman, Halis

  Background – In this study, the potential protective effects of adenosine triphosphate (ATP) and glutathione (GSH) against atezolizumab-induced cardiac injury in rat heart tissue were investigated. Methods – A total of 24 male albino Wistar rats were used in the experiment. The animals were divided into four groups: healthy group adenosine triphosphate + atezolizumab (ATAZ), GSH + atezolizumab (GHAZ), and atezolizumab alone (ATZ). ATP was administered intraperitoneally at a dose of 4 mg/kg, while GSH was administered orally at a dose of 200 mg/kg for 7 days. Atezolizumab was administered intraperitoneally to the experimental groups at a dose of 10 mg/kg twice weekly. At the end of the experiment, malondialdehyde total glutathione (tGSH), superoxide dismutase catalase, interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels in heart tissues were measured using biochemical methods. In addition, histopathological and immunofluorescence examinations were performed. Results – The results showed that oxidative stress and inflammation markers increased, whereas antioxidant parameters decreased in the atezolizumab-treated group. ATP and GSH administration significantly attenuated these changes and exerted protective effects on cardiac tissue. Conclusion – Overall, ATP and GSH ameliorated the biochemical, histopathological, and immunofluorescence changes associated with atezolizumab-induced cardiac injury in this experimental model.

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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/11244
  Mitigating Hydroxychloroquine-Induced Oxidative Liver Damage: The Roles of Adenosine Triphosphate, Liv-52, and Their Combination in Rats

  Kandefer, Meryem Yalvac; Sezgin, Esra Tuba; Suleyman, Bahadir; Cimen, Ferda Keskin; Memiş, Fulya; Gulaboglu, Mine; Suleyman, Halis

  Hydroxychloroquine (HCQ), originally developed as an antimalarial agent, has been associated with hepatotoxic effects in experimental and clinical settings. Our study was designed to evaluate the effects of this agent on liver toxicity and to understand the protective roles of adenosine triphosphate (ATP), Liver-52 (Liv-52), and their combination. Male Wistar rats (250–280 g) were randomly assigned to five groups (n = 6): healthy control (C), HCQ only (H), ATP plus HCQ (AH), Liv-52 plus HCQ (LH), and ATP–Liv-52 plus HCQ (ALH). ATP (4 mg/kg) was administered intraperitoneally once daily, whereas Liv-52 (20 mg/kg) was administered orally via gavage. One hour later, all groups except C received HCQ (120 mg/kg, orally, twice daily). All treatments were continued for seven consecutive days. At the end of the experiment, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured, and liver tissues were analyzed for malondialdehyde (MDA), total glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities, along with histopathological evaluation. HCQ administration significantly increased oxidative stress, as evidenced by elevated MDA levels (p < 0.01) and reduced antioxidant parameters, including GSH, SOD, and CAT (p < 0.05), accompanied by prominent histopathological damage. Treatment with ATP or Liv-52 markedly ameliorated these alterations by decreasing MDA and restoring antioxidant markers. The combination treatment was observed to exhibit the most pronounced protective effect; it significantly reduced MDA levels, improved GSH, SOD, and CAT levels more effectively, and produced significant decreases in AST and ALT values (p < 0.05).

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• ArticleAçık Erişim2026/r/ebyu/11226
  Comparative Protective Effects of ATP and TPP Against Olaparib-Induced Ovarian Injury in Rats: Insights from Biochemical Parameters, Histopathology, and IRE1α, Cleaved Caspase-3, LC3B, and NF-κB p65 Double Immunofluorescence

  Paltaci, Seyma Ilayda; Yilmaz, Nesrin; Kozali Uzun, Sukran; Yavuzer, Bulent; Coban, Taha Abdulkadir; Ozkaraca, Mustafa; Gungor, Ali; Yaqubov, Kamandar; Suleyman, Halis

  Background: Olaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor used to treat several malignancies. Previous studies have reported that olaparib may induce ovarian injury by elevating reactive oxygen species and impairing cellular energy homeostasis. ATP is a central regulator of intracellular energy balance and antioxidant defense, whereas thiamine pyrophosphate (TPP), the active form of vitamin B1, supports ATP biosynthesis and possesses antioxidant and anti-inflammatory properties. This study compared the protective effects of ATP and TPP against olaparib-induced ovarian injury in rats. Methods: Twenty-four female Wistar albino rats were randomly assigned to four groups (n=6 each): healthy control (HG), olaparib-only (OLP), ATP plus olaparib (ATOL), and TPP plus olaparib (TPOL). Olaparib (100 mg/kg, orally, twice daily), ATP (5 mg/kg, intraperitoneally, once daily), and TPP (25 mg/kg, intraperitoneally, once daily) were administered for 14 consecutive days. Ovarian tissue levels of oxidant (MDA), antioxidants (tGSH, SOD, CAT), and pro-inflammatory cytokine (IL-6) were determined. Tissue specimens underwent histopathological (follicular and parenchymal degeneration) and double immunofluorescence analyses (IRE1α, cleaved Caspase-3, LC3B, and NF-κB p65 immunopositivity). Results: Olaparib significantly increased oxidant and pro-inflammatory cytokine levels and decreased antioxidant levels. Histopathology revealed severe follicular and parenchymal degeneration, and immunofluorescence analysis showed significantly increased IRE1α, cleaved Caspase-3, LC3B, and NF-κB p65 immunopositivity. Both ATP and TPP pre-treatment significantly attenuated olaparib-induced oxidative stress, inflammatory responses, histopathological injury, and cellular stress marker immunopositivity. ATP demonstrated a more pronounced protective effect than TPP, particularly regarding follicular degeneration suppression and LC3B and NF-κB p65 immunopositivity. Conclusion: Olaparib induced ovarian injury accompanied by oxidative stress, cytokine-mediated inflammation, IRE1α-related endoplasmic reticulum stress, cleaved Caspase-3-related apoptosis, LC3B-related autophagy, and NF-κB-related inflammatory signaling. Both ATP and TPP attenuated olaparib-associated injury, with greater effects for ATP. These findings suggest that maintenance of cellular energy homeostasis may represent a promising strategy for attenuating PARP inhibitor-induced ovarian injury.

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• ArticleYayıncıda açık erişim2026/r/ebyu/10889
  Liv-52 Attenuates Erlotinib-Induced Liver Injury via Modulation of Oxidative Stress, Inflammation, and Apoptosis in Rats

  Bulut, Seval; Altuner, Durdu; Suleyman, Bahadir; Mammadov, Renad; Ozkaraca, Mustafa; Gungor, Ali; Kuzucu, Mehmet; Hendem, Engin; Suleyman, Halis

  Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is widely used in cancer therapy; however, hepatotoxicity limits its clinical use. This study investigated the protective effects of Liv-52, a polyherbal hepatoprotective formulation, against erlotinib-induced hepatotoxicity in rats and compared its efficacy with melatonin. The animals (n = 24, Wistar albino rats) were randomly categorized into four groups: healthy (HG), erlotinib (ERG), Liv-52 + erlotinib (LEG), and melatonin + erlotinib (MEG). Liv-52 (50 mg/kg/day, orally) and melatonin (10 mg/kg/day, orally) were administered once daily for two weeks. Erlotinib (10 mg/kg, orally) was given every other day to ERG, LEG, and MEG groups for two weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were measured. Hepatic malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) levels were analyzed. Additionally, double immunofluorescence staining was performed to evaluate apoptotic (poly[ADP-ribose] polymerase-1 [PARP-1], apoptosis-inducing factor [AIF]), inflammatory (cyclooxygenase-2 [COX-2]), and anti-inflammatory (interleukin-10 [IL-10]) biomarkers in liver tissues. Histopathological examination was also conducted to assess structural alterations. Erlotinib significantly increased MDA, ALT, AST, and LDH while decreasing tGSH, SOD, and CAT (p < 0.001). Strong immunoreactivity for PARP-1, AIF, IL-10, and COX-2, as well as severe hydropic degeneration and necrosis, was observed in ERG (p < 0.05). Both Liv-52 and melatonin significantly ameliorated biochemical, histopathological, apoptotic, and inflammatory alterations (p < 0.05). Notably, Liv-52 demonstrated superior hepatoprotective efficacy compared to melatonin. These findings indicate that Liv-52 effectively attenuates erlotinib-induced hepatotoxicity by modulating oxidative stress, inflammatory responses, and apoptotic pathways, thereby preserving liver function and structural integrity.

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