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- ArticleAçık Erişim2026Potential 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.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Liv-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.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Protective 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.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2026Flunarizine 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.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Unveiling genetic defense mechanisms: expression analysis of hym, AmNrx1, and CYP9Q3 genes in Varroa-resistant anatolian honey bees
Kabakcı, Dilek; Karataş, Ümit; Tunca, Rahşan Ivgin; Çankaya, Murat; Karabağ, Kemal; Akdeniz, Gökhan; Kuzucu, Mehmet
The Varroa destructor represents a significant threat to honey bees, leading to substantial yield losses and declines in colony health. Defense behaviors, including grooming (auto and allogrooming), serve as crucial mechanisms against Varroa infestations, yet the genetic basis of these behaviors remains elusive. This study examines the expression levels of hymenoptaecin (hym), neurexin-1 (AmNrx1), and CYP9Q3, potentially associated with defense behavior, in colonies of the Muğla honey bee ecotype (Apis mellifera anatoliaca) subjected to a Varroa selection program. Worker bees from 23 control groups and 23 colonies under selection were evaluated by using qPCR analysis. Results reveal a significant upregulation of hym, AmNrx1, and CYP9Q3 genes in the selected group, with fold changes of 2.9, 2.95, and 3.26 respectively compared to controls (p < 0.01). This suggests that selection against Varroa induces alterations in gene expression linked to Varroa exposure behaviors. These findings advocate for the potential use of hym, AmNrx1, and CYP9Q3 genes in preselection for future Varroa-resistant programs in honey bees. Supported by previous studies, these genes may facilitate the establishment of populations with enhanced defense behaviors, such as autogrooming and allogrooming.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Design and synthesis of new HCV NS3/4A protease inhibitors to effective against drug resistance
Oksuz, Zehra; Aktekin, Mine Buga; Alagoz, Mehmet Abdullah; Kuzucu, Mehmet; Serin, Mehmet Sami; Algul, Oztekin
HCV NS3/4A protease is a crucial target for antiviral therapy, but resistance remains a significant challenge. Understanding substrate recognition is key to developing effective inhibitors. The aim of this study was to investigate four new compounds (10–12 and 13) that mimic natural substrate binding. Compound activities were determined with enzymatic assays and anti-proliferative activities were evaluated. Compound 12 exhibited the highest potency with an IC50 of 17.78 μM and a Ki value of 16.39 μM. All compounds demonstrated moderate to high anti-proliferative activity against HFF-1 and HepG2 cells, with 12 and 11 showing the most potent effects. In silico studies revealed that compounds 11 and 12 formed stable complexes with the HCV NS3/4A protease, establishing significant interactions with key residues of the catalytic triad. Their docking scores and molecular dynamics simulations were comparable to those of the reference molecule, simeprevir. These findings suggest that compounds 10–12 and 13 hold promise as potential therapeutic agents against HCV, warranting further investigation.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Protective effect of deinoxanthin in sorafenib-induced nephrotoxicity in rats with the hepatocellular carcinoma model
Karasu, Nilgun; Kuzucu, Mehmet; Mat, Ozge Cengiz; Gul, Mustafa; Yay, Arzu; Dundar, Munis
Sorafenib is a synthetic compound and an orally administered multichines inhibitor that targets growth signaling and angiogenesis. It is widely recognized as the standard of care for advanced hepatocellular carcinoma (HCC) but has toxic side effects. Deinoxanthin, purified from the radioresistant bacterium Deinococcus radiodurans, has strong antioxidant characteristics. In this study, the protective effect of deinoxanthin against sorafenib-induced nephrotoxicity was investigated in a rat model of hepatocellular carcinoma. In this regard, the expressions of DDAH1, KIM1, and INOS genes were examined, histopathological and immunohistochemical analyses were performed, and various parameters such as SOD, MDA, GST, CAT, TAS, and TOS were tested biochemically. BUN and creatinine levels were measured in renal tissues. RT-qPCR, Western blot, and ELISA methods were used for all these analyses. As a result, the analyses show that deinoxanthin, which has a high antioxidant capacity, reduces kidney injury and can be used as a protective agent. The primary objective of this study is to evaluate the potential of deinoxanthin as a protective agent against the nephrotoxic side effects of sorafenib in HCC. Our study identified the potential synergistic effects of sorafenib and deinoxanthin on nephrotoxicity in rats with hepatocellular carcinoma.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Analysis of possible effects of recombinant antimicrobial peptide TP4 on colon cancer line HT-29
Kılınç, Seda; Karaoğlan, Mert; Kuzucu, Mehmet
Tilapia piscidin 4 (TP4) is a 25-amino-acid cationic antimicrobial peptide derived from Nile tilapia (Oreochromis niloticus). TP4 has demonstrated strong antimicrobial activity against a broad range of pathogens and exhibits additional biological functions, including wound healing and anticancer activity. In a previous study, recombinant TP4 peptide was produced in the Pichia pastoris KM71H expression system and purified by Ni–NTA affinity chromatography. The aim of this study was to evaluate and compare the cytotoxicity of recombinant TP4 against HT-29 colon cancer and HGF-1 healthy gingival fibroblast cells.The antimicrobial activity of TP4 was first assessed using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays, confirming its efficacy. Subsequently, the cytotoxic effects of TP4 on HT-29 and HGF-1 cells were further analyzed using the MTT, lactate dehydrogenase (LDH), total antioxidant/oxidant status (TAS/TOS), and malondialdehyde (MDA) assays. TP4 disrupted the antioxidant balance in both cell types, with a significant increase in the oxidant levels and a marked decrease in the antioxidant levels in HT-29 cells. The IC50 values of TP4 were determined to be 15 μg/mL for HT-29 cells and 25 μg/mL for HGF-1 cells. Apoptosis assays, including Annexin V & Dead Cell, RT-qPCR, and ELISA, revealed that TP4 induced apoptosis predominantly in HT-29 cells, as evidenced by the upregulation of BAX and CASP3 and the downregulation of the BCL-2. In conclusion, TP4 exhibited selective and potent apoptotic effects on HT-29 colon cancer cells, suggesting its potential as a novel therapeutic agent for colon cancer treatment.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Enhanced Production and Therapeutic Evaluation of TP4 Peptide in Pichia pastoris Against Hepatocellular Carcinoma HUH-7 Cells
Kuzucu, Mehmet; Karaoğlan, Mert; Kılınç, Seda
Tilapia piscidin 4 (TP4), a cationic antimicrobial peptide, is recognized for its diverse biological roles, including antibacterial, wound-healing, and anticancer properties. Herein, the codon-optimized sequence of TP4 peptide was expressed using the pPICZαA expression vector containing the AOX1 promoter, a strong and inducible promoter, in the Pichia pastoris KM71H expression system. Recombinant TP4 peptide was purified by Ni-NTA affinity chromatography. After purification, the anticancer activity of TP4 was assessed in HUH-7 hepatocellular carcinoma cells, and the underlying mechanisms were determined. In the present study, it was demonstrated for the first time that recombinant TP4 displayed strong anticancer activity in the human HUH-7 cell line. The TP4 antimicrobial peptide can be used as a competitive candidate for the treatment of cancer cells due to its anticancer effects.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024AuNPs with Cynara scolymus leaf extracts rescue arsenic-induced neurobehavioral deficits and hippocampal tissue toxicity in Balb/c mice through D1R and D2R activation
Cicek, Betul; Hacimuftuoglu, Ahmet; Yeni, Yesim; Kuzucu, Mehmet; Genc, Sidika; Cetin, Ahmet; Yavuz, Emre; Danısman, Betul; Levent, Akin; Ozdokur, Kemal Volkan
The present study was designed to evaluate whether AuNPs (gold nanoparticles) synthesized with the Cynara scolymus (CS) leaf exert protective and/or alleviative effects on arsenic (As)-induced hippocampal neurotoxicity in mice. Neurotoxicity in mice was developed by orally treating 10 mg/kg/day sodium arsenite (NaAsO2) for 21 days. 10 µg/g AuNPs, 1.6 g/kg CS, and 10 µg/g CS-AuNPs were administered orally simultaneously with 10 mg/kg As. CS and CS-AuNPs treatments showed down-regulation of TNF-α and IL-1β levels. CS and CS-AuNPs also ameliorated apoptosis and reduced the alterations in the expression levels of D1 and D2 dopamine receptors induced by As. Simultaneous treatment with CS and CS-AuNPs improved As-induced learning, memory deficits, and motor coordination in mice assessed by water maze and locomotor tests, respectively. The results of this study provide evidence that CS-AuNPs demonstrated neuroprotective roles with antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as improving D1 and D2 signaling, and eventually reversed neurobehavioral impairments.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Effect of tangeretin on cisplatin-induced oxido-inflammatory brain damage in rats
Cicek, Betul; Danisman, Betul; Bolat, Ismail; Kiliclioglu, Metin; Kuzucu, Mehmet; Suleyman, Halis; Tsarouhas, Konstantinos; Tsatsakis, Aristidis; Taghizadehghalehjoughi, Ali
Cisplatin (CIS) is a platinum-derived chemotherapeutic agent commonly utilized in the treatment of various malignant tumours. However, anticancer doses of the drug cause serious damage to the brain. This study aimed to determine the potential protective effects of tangeretin, which has antioxidant and anti-inflammatory properties, in cisplatin-induced neurotoxicity on BALB/c mice brains. Male BALB/c mice were randomized and separated into four groups. Tangeretin was given for 10 days by gavage. CIS was injected as a single dose of 10 mg/kg intraperitoneally (ip) on the 10th day. Brain tissues, malondialdehyde (MDA), total glutathione (tGSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and nitric oxide (NO) levels were measured to determine oxidative damage and myeloperoxidase, tumour necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), IL-6 and IL-10 were measured to determine inflammatory activity. In addition, 8-OHdG and caspase-3 were analysed by immunofluorescence methods. While CIS administration remarkably elevated reactive oxygen species, MDA, and NO levels in brain tissue compared to the control, tGSH, GPx, SOD and CAT levels were significantly decreased. Also, it has been detected that TNF-α, IL-1β and IL-6 obtained in CIS-treated groups increased as well as IL-10 decreased, thereby elevating the inflammatory response. In addition, 8-OHdG and caspase-3 immunoreactivity in neurons increased with CIS administration. Treatment with tangeretin ameliorated the deterioration in oxidant/antioxidant status, overpowered neuroinflammation and ameliorated neurotoxicity-induced apoptosis. This study shows that tangeretin has beneficial effects on CIS-induced neurodegeneration. Possible mechanisms underlying these beneficial effects include the antioxidant and anti-inflammatory properties of tangeretin.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Morinda citrifolia protective effects on paclitaxel-induced testis parenchyma toxicity: An experimental study
Genc, Sidika; Cicek, Betul; Yeni, Yesim; Kuzucu, Mehmet; Hacimuftuoglu, Ahmet; Bolat, Ismail; Yildirim, Serkan; Zaker, Himasadat; Zachariou, Athanasios; Sofikitis, Nikolaos
The current study aimed to investigate the sensitivity of male testis parenchyma cells to chemotherapy agents and the protective effects and mechanisms of Morinda citrifolia (Noni) administration against structural and functional changes before and after chemotherapy (Paclitaxel (PTX)). For this purpose, rats were randomly assigned into four groups (Control = G1, PTX 5 mg/kg = G2; PTX + Noni 10 mg/kg = G3, PTX + Noni 20 mg/kg = G4). PTX was injected intraperitoneally for 4 consecutive weeks, at a dose of 5 mg/kg to all groups except the control group. Then noni was administrated in 10 (G3) and 20 (G4) mg/kg groups orally (gavage) for 14 days. Biochemical analyses, Real-Time Polymerase Chain Reaction (PCR), and immunohistochemical analyses were performed. According to our results, Total Oxidative Stress (TOS) and Malondialdehyde (MDA) were significantly increased in the PTX group (P < 0.01). Superoxide Dismutase (SOD) enzyme activity and Total Antioxidant Capacity (TAC) levels were decreased (P < 0.01). The changes in the rats treated with PTX + Noni 20 mg/kg were noteworthy. The increased levels of IL1-β (Interleukin 1 beta) and TNFα (tumor necrosis factor-alpha) with PTX were down-regulated after treatment with PTX + Noni 20 mg/kg (P < 0.01) (9 % and 5 % respectively). In addition, Noni restored the testicular histopathological structure by reducing caspase-3 expression and significantly (61 %) suppressed oxidative DNA damage and apoptosis (by regulating the Bax (bcl-2-like protein 4)/Bcl-2 (B-cell lymphoma gene-2) ratio). In conclusion, Noni reduced cellular apoptosis and drastically changed Caspase 8 and Bax/Bcl-2 levels. Furthermore, it considerably decreases oxidative damage and can be used in testicular degeneration.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Synthesis and evaluation of di-heterocyclic benzazole compounds as potential antibacterial and anti-biofilm agents against Staphylococcus aureus
Aktekin, Mine Buga; Oksuz, Zehra; Turkmenoglu, Burcin; Istifli, Erman Salih; Kuzucu, Mehmet; Algul, Oztekin
Cumulative escalation in antibiotic-resistant pathogens necessitates the quest for novel antimicrobial agents, as current options continue to diminish bacterial resistance. Herein, we report the synthesis of di-heterocyclic benzazole structures (12–19) and their in vitro evaluation for some biological activities. Compounds 16 and 17 demonstrated potent antibacterial activity (MIC = 7.81 μg/mL) against Staphylococcus aureus, along with significant anti-biofilm activity. Noteworthy is the capability of Compound 17 to inhibit biofilm formation by at least 50% at sub-MIC (3.90 μg/mL) concentration. Furthermore, both compounds exhibited the potential to inhibit preformed biofilm by at least 50% at the MIC concentration (7.81 μg/mL). Additionally, Compounds 16 and 17 were examined for cytotoxic effects in HFF-1 cells, using the MTT method, and screened for binding interactions within the active site of S. aureus DNA gyrase using in silico molecular docking technique, employing AutoDock 4.2.6 and Schrödinger Glidse programs. Overall, our findings highlight Compounds 16 and 17 as promising scaffolds warranting further optimization for the development of effective antibacterial and anti-biofilm agents.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Deinoksantinin HER2 Pozitif Meme Kanserinde Tamoksifenin Antiproliferatif Aktivitesi Üzerindeki Agonistik Etkileri: MDA-MB-453 Üzerine Bir In vitro Çalışma
Kuzucu, Mehmet; Günay, Nihan
2020 yılında dünya genelinde 684.996 kadının öldüğü tahmin edilen meme kanserinin patogenezinin iyi anlaşılması, tedavi yöntemlerinin geliştirilmesinde hayati bir rol oynamaktadır. Son yıllarda östrojen reseptörü (ER), progesteron reseptörü (PR), Epidermal Büyüme Faktör reseptörü-2 (HER2) ifade düzeyleri önemli prognostik belirteçler olmuştur. Kombinasyonel terapi yaklaşımı, iki veya daha fazla aktif maddenin veya yöntemin kullanılmasıdır. Bu tedavi yönteminde en önemli kazanç karsinomun aynı anda birden fazla ilaca karşı direnç gösterme olasılığının düşük olması sebebiyle ilaç direnci gelişimini azaltmaktır. Östrojen reseptörü yarışmalı ve steroid olmayan bir bileşik olan Tamoksifen, hormon reseptör pozitif meme kanseri olan hastaları tedavi etmek için yaklaşık 20 yıldır kullanılmaktadır. Deinoksantin, radyasyona dirençli bir bakteri olan Deinococcus radiodurans'ın hücre duvarından saflaştırılan bir ksantofil türevidir. Bu ksantin türevinin bazı kanser türleri üzerinde proapoptotik ve antiproliferatif etkilere sahip olduğu bazı çalışmalarda gösterilmiştir. Çalışma kapsamında Tamoksifen'in deinoksantin ile etkinliğinin artırılması hedeflendi. Tamoksifen ve deinoksantinin MDA-MB-453 meme kanseri hücre hattı üzerindeki sinerjik etkisini araştırmak için ACTB geni referans olarak kullanılarak; BAX, CASP-3, BCL-2 ve HER2 genlerinin ifade seviyeleri RT-qPCR yöntemi ile incelenmiştir. BAX, CASP-3, BCL-2 ve HER2 proteinlerinin miktarları ELISA yöntemi ile belirlenmiş ve RT-qPCR sonuçları ile karşılaştırılmıştır. Tamoksifenin HER2 pozitif meme kanseri hücre hattı üzerindeki antiproliferatif etkisinin deinoksantin kombinasyonu ile arttığı belirlendi.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2023Effect of the aerobic power test performed at low-medium altitude on the myostatin, pgc-1 alpha and klotho levels
Tetik Dündar, Sibel; Kuzucu, Mehmet; Varol, S. Rana
BACKGROUND: The aim of this study was to investigate the influence of the aerobic power test on myostatin, PGC-1, and Klotho levels in athletes who had acclimatized to the altitude. MethodS: a total of twenty athletes consisting of nine women and eleven men with an age average of 19.80±2.587 who were engaged in cross-country skiing at elite level participated in the study. the study was carried out at a ski center (altitude: 2000 m). the participants were measured for age, height, body mass (by standard methods), aerobic power test, blood lactate level after rest and aerobic power test. Blood was obtained from the (basal) antecubital vein in the fasting condition before to the aerobic power test. two hours and 48 hours after the test, blood taking was repeated. Klotho, myostatin and PGC-1α levels were examined in the serum samples by the ELISA device and MicroELISA method. RESULTS: As a result, the aerobic power test which lasted 15 minutes significantly increased the PGC-1α (31.2%) and Klotho (332.8%) levels (P<0.016). The serum, on the other hand, had no effect on the level of myostatin (7.2%) cheval (P>0.016). CONCLUSIONS: Acute exercise (single repetition) was found to be effective even on elite athletes who had adapted to the altitude. Myostatin level did not change with the aerobic power test performed at low-mid altitude, but PGC-1α and Klotho levels increased.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries
Cicek, Betul; Hacimuftuoglu, Ahmet; Kuzucu, Mehmet; Cetin, Ahmet; Yeni, Yesim; Genc, Sidika; Yildirim, Serkan; Bolat, Ismail; Kantarci, Mecit; Gul, Mustafa
According to population-based studies, lung cancer is the prominent reason for cancer-related mortality worldwide in males and is also rising in females at an alarming rate. Sorafenib (SOR), which is approved for the treatment of hepatocellular carcinoma and renal cell carcinoma, is a multitargeted protein kinase inhibitor. Additionally, SOR is the subject of interest for preclinical and clinical trials in lung cancer. This study was designed to assess in vivo the possible effects of sorafenib (SOR) in diethylnitrosamine (DEN)-induced lung carcinogenesis and examine its probable mechanisms of action. A total of 30 adult male rats were divided into three groups (1) control, (2) DEN, and (3) DEN + SOR. The chemical induction of lung carcinogenesis was performed by injection of DEN intraperitoneally at 150 mg/kg once a week for two weeks. The DEN-administered rats were co-treated with SOR of 10 mg/kg by oral gavage for 42 alternate days. Serum and lung tissue samples were analyzed to determine SRY-box transcription factor 2 (SOX-2) levels. The tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels were measured in lung tissue supernatants. Lung sections were analyzed for cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) histopathologically. In addition, cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) were analyzed by immunohistochemistry and immunofluorescence methods, respectively. SOR reduced the level of SOX-2 that maintenance of cancer stemness and tumorigenicity, and TNF-α and IL-1β levels. Histopathological analysis demonstrated widespread inflammatory cell infiltration, disorganized alveolar structure, hyperemia in the vessels, and thickened alveolar walls in DEN-induced rats. The damage was markedly reduced upon SOR treatment. Further, immunohistochemical and immunofluorescence analysis also revealed increased expression of COX-2 and JNK expression in DEN-intoxicated rats. However, SOR treatment alleviated the expression of these inflammatory markers in DEN-induced lung carcinogenesis. These findings suggested that SOR inhibits DEN-induced lung precancerous lesions through decreased inflammation with concomitant in reduced SOX-2 levels, which enables the maintenance of cancer stem cell properties.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Taxifolin as a novel therapeutic agent for epileptic seizures induced by caffeine-induced oxidative stress in rats
Yasar, Hasan; Altuner, Durdu; Bulut, Seval; Cicek, Betul; Gursul, Cebrail; Kuzucu, Mehmet; Suleyman, Halis
Background. Epilepsy is a severe neurological disease that results from excessive and/or synchronized neuronal activity in the brain, and oxidative stress plays a role in its pathogenesis. Taxifolin is a flavonoid that exhibits antioxidant activity. Objectives. To investigate the effects of taxifolin on caffeine-induced epileptic seizures in rats and reveal the role of antioxidant activity in antiepileptic therapy. Materials and methods. Forty rats were divided into 4 groups (n = 6/group): caffeine 300 mg/kg group (CG), taxifolin 50 mg/kg + caffeine 300 mg/kg group (TCG), 2 mg/kg diazepam + 300 mg/kg caffeine group (DCG), and a healthy group (HG). Taxifolin was given to the TCG, and diazepam was given to the DCG orally. One hour later, caffeine was injected intraperitoneally into the CG, TCG and DCG rats. The time between the caffeine injection and the contractions (the latency period) was determined. Animals were euthanized 1 h after caffeine injection, and brain tissues were biochemically examined for oxidants and antioxidants. Results. Taxifolin and diazepam prolonged the latency period to a similar extent (p = 0.549), while taxifolin was more successful in preventing mortality. Taxifolin suppressed the caffeine-induced increase in myeloperoxidase, total oxidant status and oxidative stress index, and decreased total glutathione, superoxide dismutase and total antioxidant status more effectively than diazepam (p < 0.05). Conclusions. We showed the relationship between antioxidant activity and epilepsy treatment, and demonstrated that taxifolin may be useful for treating epilepsy.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Tocilizumab is effective in preventing ovarian injury induced by ischemia-reperfusion in rats
Uzel, Kemine; Lakhno, Igor; Turkler, Can; Kuzucu, Mehmet; Yazici, Gulce Naz; Mammadov, Renad; Suleyman, Bahadir; Kale, Ahmet; Suleyman, Halis
Ovarian torsion can be defined as the bending of the ovaries on the supporting ligament, disrupting both venous and arterial blood circulation. Insufficient blood flow causes ovarian tissue hypoxia and leads to ischemia. This study aimed to investigate whether tocilizumab has a protective effect on ischemia-reperfusion injury due to ovarian torsion in rats. Eighteen female Wistar albino rats were divided into three equal groups (Sham (SG), ischemia-reperfusion (OIR), and ischemia-reperfusion+tocilizumab (OIRT)). Degeneration, necrosis, vascular dilatation/congestion, interstitial edema, hemorrhage, and polymorphonuclear lymphocyte (PMNL) infiltration scores were significantly different between the groups (p=0.001 for all parameters). Moreover, the OIRT group had a significant improvement in these criteria compared to the OIR group (p<0.05). Additionally, there was a considerable difference between OIRT and OIR groups in the number of primordial, developing, and atretic follicles groups (p<0.05), while there was no difference in the number of corpus luteum (p=0.052). Stress markers or cytokines, such as MDA, tGSH, NF-κB, TNF-α, IL-1β, and IL-6, were significantly different between groups (p<0.05). Furthermore, a significant improvement was found in the measured variables when the OIRT group was compared with the OIR group (p<0.05). Tocilizumab may be an alternative option for treating ischemia-reperfusion injury due to ovarian torsion.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Flavonoid-Rich Sambucus nigra Berry Extract Enhances Nrf2/HO-1 Signaling Pathway Activation and Exerts Antiulcerative Effects In Vivo
Cicek, Betul; Danısman, Betul; Yildirim, Serkan; Yuce, Neslihan; Nikitovic, Dragana; Bolat, Ismail; Kuzucu, Mehmet; Ceyran, Ertuğrul; Bardas, Ebru; Golokhvast, Kirill S.
Sambucus nigra (SN) berry extract is characterized by high antioxidant and anti-inflammatory activity. The current study aimed to investigate the effect of SN berry extract against indomethacin (IND)-induced gastric ulcer in rats and the mechanism involved. SN berry extract alleviated IND-induced gastric ulcers, as shown by assessing pathological manifestations in the gastric mucosa. These protective effects are attributed to attenuated oxidative damage to the gastric mucosa, correlated to increased activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), enhanced glutathione (GSH) levels, total antioxidant capacity (TAC), and upregulation of the Nrf2/HO-1 cascade. Moreover, oxidative stress markers, including malondialdehyde (MDA) and total oxidant status (TOS), were downregulated in SN-extract-treated animals. Furthermore, SN berry extract suppressed gastric mucosal inflammation by downregulating interleukin (IL)-33, IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels, and attenuating myeloperoxidase (MPO) activity. The protective effects of SN berry extract were similar to those exerted by esomeprazole (ESO), an acid-secretion-suppressive drug. In conclusion, SN berry extract has antiulcerative effects, alleviating oxidative stress and inflammation.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Extremophilic Solutions: The Role of Deinoxanthin in Counteracting UV-Induced Skin Harm
Kuzucu, Mehmet
This research delved into the protective capacities of deinoxanthin, a carotenoid present in Deinococcus radiodurans, against UVA- and UVB-mediated skin damage using human fibroblast foreskin cells (HFF-1). Using the MTT assay, HFF-1 cells treated with 10 µM DNX displayed 20% and 31.7% higher viability than the positive (Vitamin C-treated) and negative (DNX-untreated) control groups, respectively, upon 100 mJ/cm2 UVB exposure. At 24 J/cm2 UVA, 20 µM DNX-treated cells showed 80.6% viability, exceeding the positive and negative control groups by 28.6% and 33.6%, respectively. Flow cytometry analysis revealed that cells treated with DNX and exposed to 24 J/cm2 UVA exhibited a 69.32% reduction in apoptotic processes compared to untreated cells. Similarly, when exposed to 100 mJ/cm2 UVB, DNX-treated cells demonstrated a 72.35% decrease in apoptotic processes relative to their untreated counterparts. DNX also displayed dose-dependent inhibition on tyrosinase activity. The study emphasized DNX’s antioxidative capacity, evident in its modulation of superoxide dismutase activity and measurements of Malondialdehyde and intracellular reactive oxygen species levels. DNX-treated cells exhibited higher hydroxyproline levels, suggesting healthier collagen production. Additionally, the wound-healing assay method confirmed an accelerated healing rate in DNX-treated cells. Conclusively, DNX offers significant protection against UV-induced skin damage, emphasizing its potential for skincare and therapeutics.
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