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Öğe A histological examination of the effects of Ferula elaeochytris extract on kidney and liver tissues in myoglobinuric acute renal failure(Taylor & Francis Ltd, 2024) Yildiz, Fatma; Gungor, Meltem; Sezginer, Perihan; Aksak, TiinceMyoglobinuric acute renal failure (MARF) is a structural and functional disorder that occurs in the kidney following the release of muscle cell contents into the circulation. In this present study, possible protective and curative effects of Ferula elaeochytris extract against kidney and liver damage in experimentally induced MARF in a rat model were investigated. 3-4 Month-old, 200-250 g Sprague Dawley rats were divided into 8 equal groups with 7 rats per group. Group I was a no-intervention Control group. All groups except for the Group I were dehydrated for 16 hours. Following this dehydration, 50% v/v aqueous glycerol solution was injected into both hind leg muscles of the animals, at a dose of 8 ml/kg. The rats were given physiological saline (SF) once orally before the model was administered (Group II) and after the model was administered (Group V). Similarly, two different doses of Ferula elaeochytris root extract (40 mg/kg and 80 mg/kg) were dissolved in 2 ml of SF and administered orally before (Groups III and IV) and after (Group VI, VII) the model was created. Following the experimental period, kidney and liver tissues were removed from all groups, and fixed in 10% neutral formaldehyde solution for light microscopic examinations. Intracellular vacuolization, enlargement in the Bowman's space, widespread atrophy in the tubular structures, luminal enlargement, and desquamation were detected in the kidney tissue sections of all the experimental model groups. In the liver tissue sections, was detected hepatocyte degeneration, intracellular vacuolization, irregularity in cell membrane borders, and apoptotic bodies. These histopathological consequences of MARF were evaluated for all groups, and whereas a curative effect of Ferula elaeochytris could be seen, its protective effect was higher than its curative effect.Öğe Effect of combination treatment of protocatechuic acid with 5-fluorouracil and oxaliplatin on colon cancer Caco-2 cell line(Natl Inst Science Communication-Niscair, 2023) Yildiz, Fatma; Eciroglu, Hamiyet; Ovey, Ishak Suat; Avnioglu, SedaAmong the most common antitumor drugs used in the treatment of colon cancer are 5-fluorouracil and oxaliplatin (5-FU and OXA). However, both these drugs have many side effects, and hence there is a need for new treatment\approach to reduce the side effects aas well as drug concentration. In this context, here, we investigated the effect of addition of protocatechuic acid (PCA) onto either monotherapies or combination therapies of 5-FU and OXA on the human colon cancer (Caco-2) cell line. In addition, we did evaluate the synergistic effect of PCA with 5-FU and OXA. Further, we determined the suppressive effects of different doses of PCA alone or in combination with 5-FU/OXA on cell proliferation after 24 and 48 hours. We identified a suppressive effect of PCA on cell viability at 48 h starting from the dose of 50 mu M Matrix metalloproteinase-2 (MMP-2) and MMP-9 gene expression levels and apoptotic effects showed significant increases and decreases depending on the dose and time applied in the experimental groups. The highest synergistic activity was seen at 2:1 concentration of 5-FU+ PCA. Our findings indicate the presence of the cytotoxic and apoptotic effects of PCA in Caco-2 cells at 48 h, increasing with a dose-and time-dependent manner.Öğe Evaluating the Neuroprotective and Acetylcholinesterase Inhibitory Properties of Four Calcineurin Inhibitor Drugs: Tacrolimus, Pimecrolimus, Cyclosporin A, and Voclosporin(Springer, 2025) Kocanci, Fatma Gonca; Sarban, Hamiyet Eciroglu; Yildiz, FatmaNeurodegenerative diseases (ND), marked by progressive neuronal degeneration, often involve dysregulation of acetylcholinesterase (AChE), a key enzyme in cholinergic neurotransmission. AChE inhibition is a well-established therapeutic strategy for Alzheimer's disease (AD), the most prevalent ND, as it aims to restore impaired cholinergic function. However, the effects of calcineurin inhibitors (CNIs), primarily used as immunosuppressants, on AChE activity remain largely unexplored. Recent evidence suggests CNIs possess neuroprotective properties, highlighting their potential for ND treatment. This study evaluated the binding affinities of FDA-approved CNIs-Tacrolimus (Tac), Pimecrolimus (Pim), Cyclosporine A (Csa), and Voclosporin (Voc)-to AChE via molecular docking and molecular dynamic simulation. AChE inhibition was assessed in vitro using the Ellman method and in H2O2-induced degenerative neuron-like SH-SY5Y cells via ELISA and qRT-PCR. Neuroprotection was examined through MTT assays and neurite analysis. Additionally, the antiapoptotic effect was examined by ELISA analysis measuring caspase-3. Docking studies confirmed strong AChE binding for all CNIs, with Voc exhibiting the highest affinity. Voc demonstrated superior in vitro AChE inhibition, surpassing galantamine at low concentrations. Cellular assays showed that CNIs, particularly Voc, significantly inhibited AChE expression at the gene level. Moreover, Voc markedly restored cell viability and reduced neuronal degeneration in H2O2-treated cells. These findings suggest CNIs, especially Voc, as promising candidates for ND treatment, targeting AChE overactivity and oxidative stress.Graphical AbstractCreated in BioRender. Hamiyet Eciroglu Sarban, (2025) https://BioRender.com/q77r137Öğe Expression and diagnostic potential of circulating miR-107, miR-134-5p, miR-149-5p, miR-370-3p, and miR-221 in prostate cancer and benign prostatic hyperplasia: A preliminary study(Page Press Publications, 2025) Akkoç, Ali; Sarban, Hamiyet Eciroglu; Yildiz, Fatma; Günizi, Ozlem Ceren; Uçar, MuratBackground: MicroRNAs (miRNAs) have shown promise as diagnostic biomarkers for prostate cancer (PCa). This study aimed to evaluate the expression of miR-107, miR-134-5p, miR-149-5p, miR-370-3p, and miR-221 in whole blood to distinguish PCa from benign prostatic hyperplasia (BPH) and potentially reduce unnecessary biopsies. Methods: Whole blood samples were collected from 20 PCa patients, 17 histologically-confirmed BPH patients (all with PSA > 4 ng/mL), and 20 healthy controls over 60 years without symptoms suggesting prostatic disease and PSA < 4 ng/mL. miRNA levels were quantified using qRT-PCR. Diagnostic potential was assessed via correlation analyses with clinical parameters and ROC curve evaluation. Statistical significance was set at p < 0.05. Results: miR-107, miR-134-5p, miR-149-5p, and miR-370-3p were significantly overexpressed in PCa patients compared to BPH (p < 0.0001). ROC analysis identified miR-134-5p (AUC: 0.94) and miR-149-5p (AUC: 0.93) as strong predictors of PCa. Additionally, miR-149-5p showed a positive correlation with PSA levels (r = 0.2627, p < 0.05). Conclusions: This preliminary study demonstrated that miR-107, miR-134-5p, miR-149-5p, and miR-370-3p were significantly overexpressed in PCa patients compared to the BPH group. ROC analysis highlighted their diagnostic potential in distinguishing BPH from PCa. Despite the limited sample size, these findings provide early evidence to guide future research on the diagnostic value of miRNAs in prostate cancer. © 2025, Page Press Publications. All rights reserved.Öğe Investigation of neuroprotective effects of newly synthesized benzimidazolium salt against neurotoxicity in differentiated SH-SY5Y neuronal cells(Academic Press Inc Elsevier Science, 2025) Yildiz, FatmaNeurodegenerative diseases (ND) are a group of neurological disorders characterized by various pathological features such as selective neuronal loss, chronic inflammation, and aggregation of specific proteins. This study aimed to investigate the possible protective effects of newly synthesized benzimidazolium salt (BS) against H2O2-induced oxidative stress in differentiated SH-SY5Y cells. Firstly, retinoic acid was applied to SH-SY5Y cells to obtain mature neurons. Then, a toxicity model was created by H2O2 treatment of neuron-like differentiated SH-SY5Y (d- SH-SY5Y) cells. Survival rates of d-SH-SY5Y cells were determined using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) method. In addition, pro-inflammatory cytokine (tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) levels were determined by ELISA method, while gene expression levels of apoptotic markers (Bax, Bcl-2, caspase-3 and caspase-8) were determined by RT-QPCR method. In addition, the effect of BS on neurite length in these cell groups was evaluated through morphological observations. According to our results, BS showed neuroprotective effect by increasing cell viability against H2O2-induced neurotoxicity in d-SH-SY5Y cells (p < 0.01). BS pretreatment provided H2O2-induced Bcl-2 up-regulation, Bax down-regulation, caspase-3 activation and caspase-8 inhibition. In addition, BS supported the decrease in TNF-alpha, IL-1 beta and IL-6 protein levels. This study demonstrated for the first time that BS exhibited potential neuroprotective effects on H2O2-induced neuronal damage by attenuating inflammation and apoptosis. These findings suggest that BS may be considered a promising candidate in preventing and treating oxidative stress-mediated neurodegenerative diseases.Öğe Investigation of the Neuroprotective Effect of Riluzole on Matrix Metalloproteinases in an Experimental Model of Glaucoma(Wolters Kluwer Medknow Publications, 2024) Yildiz, Fatma; Sahinoglu-Keskek, Nedime; Yilmaz, Isil Tan; Candan, Ibrahim Aydin; Korkmaz, Orhan TanselPurpose: To investigate the neuroprotective effect of riluzole through matrix metalloproteinase-2 (MMP-2) and MMP-9 in rats, in an experimental glaucoma model. Methods: A total of 28 Wistar albino rats, 3-4 months old, weighing 250-300 g, were divided into four groups; Group I (control), Group II (glaucoma), Group III (glaucoma + corn oil + dimethyl sulfoxide (DMSO), and Group IV (glaucoma + corn oil + DMSO + riluzole). A glaucoma model was created by episcleral vein cauterization in the left eyes of Group II, III, and IV subjects. After the formation of the model, daily intraperitoneal riluzole (5 mg/kg) administration was started. At the end of 7 weeks, retinal tissues were taken and some parts of them were stained with hematoxylin and eosin for histopathological examinations. In the other part, MMP-2 and MMP-9 expressions were determined using real-time quantitative PCR and immunohistochemical techniques. Results: As a result, a statistically significant increase in intraocular pressures (IOP) was found in Groups II, III, and IV when compared with the control eyes after 7 weeks (P < 0.001). There was a decrease in IOP in the riluzole group compared to the glaucoma group. Expression levels in both genes decreased slightly with riluzole administration. In the histopathological evaluation of the groups, it was observed that there were no significant differences between the findings of degeneration in ganglion cells, hemorrhage, and differentiation in layers. Conclusions: MMP-2 and MMP-9 exhibited decreased expression levels in both Group III (glaucoma + corn oil + DMSO) and Group IV (glaucoma + corn oil + DMSO + 5 mg/kg riluzole) compared to the glaucoma groups in Group II. Given that both Group III and Group IV received injections of corn oil + DMSO, this conclusion was drawn.Öğe LoxBlock-1 or Curcumin attenuates liver, pancreas and cardiac ferroptosis, oxidative stress and injury in Ischemia/reperfusion-damaged rats by facilitating ACSL/GPx4 signaling(Churchill Livingstone, 2023) Kar, Fatih; Yildiz, Fatma; Hacioglu, Ceyhan; Kar, Ezgi; Donmez, Dilek Burukoglu; Senturk, Hakan; Kanbak, GungorIn this study, the effects of the pretreatment of Curcumin and LoxBlock-1 on liver, pancreas, and cardiac dysfunction following Ischemia-Reperfusion-induced (IR) Acute Kidney Injury (AKI) were investigated through the mechanisms of oxidative stress and ferroptosis. Total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) parameters in the tissue were analyzed to investigate the oxidative stress occurring in the liver, pancreas, and heart, and Acyl-Coa synthetase long-chain family member (ACSL4). Glutathione peroxidase 4 (GPx4) enzyme levels were also analyzed by ELISA to investigate the effect on ferroptosis. In addition, hematoxylin-eosin staining was performed for histopathological examination of the tissues. As a result of biochemical analyzes, it was observed that oxidative stress parameters increased significantly in the IR group. In addition, while the ACSL4 enzyme level increased in the IR group in all tissues, the GPx4 enzyme level decreased. In the histopathological examination, it was observed that IR caused serious damage to the heart, liver, and pancreas tissues. The present study shows that Curcumin and LoxBlock-1 have a protective effect on the liver, pancreas, and cardiac ferroptosis following the effect on AKI. In addition, Curcumin was found to be more effective than LoxBlock-1 in I/R injury with its antioxidant property.Öğe Phytochemical examination of Cistus laurifolius extract and its impact on cytotoxicity, apoptosis and oxidative stress in colorectal and breast cancer cell lines(Elsevier Gmbh, 2024) Yildiz, Fatma; Sarban, Hamiyet Eciroglu; Kocanci, Fatma Gonca; Gungor, Meltem; Yucel, Ersin; Yucel, DilgeIntroduction: Colon and breast cancer are the most common types of cancer worldwide. This study investigatesd the anticancer properties of Cistus laurifolius L. leaf extract on breast cancer (MCF-7) and human colon cancer (Caco-2) cell lines. Methods: The research involved meticulous collection, drying and processing of C. laurifolius leaves to extract bioactive compounds, subsequently analyzed for phenolic content using advanced LC-MS/MS technology. Cell viability of the extract on MCF-7 and Caco-2 cells was demonstrated by MTT test. Levels of critical apoptotic markers (Bad, Bax/Bcl-2, Bax/Bcl-xl, Caspase-9) and Total Antioxidant Capacity (TAC) and Total Oxidant Capacity (TOC), which affect the antioxidant system, were evaluated by the ELISA method. Identification of phenolic compounds, including quercetin and rutin, through target prediction analysis enriches our understanding of bioactive molecules. Results: The results of the study showed that C. laurifolius extract inhibited cell proliferation time and dose-dependent on Caco-2 and MCF-7 cells (P<0.05). TAC, Bax/Bcl-2 and Bax/Bcl-xl ratios in MCF-7 and Caco-2 cells increased in a dose-dependent manner compared to the control group. In MCF-7 cells, TAC (p<0.05; p<0.01), Bax/Bcl-2 (p<0.001; p<0.0001) and Bax-Bcl-xl (p<0.01) ratios increased at 24 h compared to the control group. In Caco-2 cells, TAC (p<0.001), Bax/Bcl-2 ratios increased at 48 h (p<0.05), while Bax-Bcl-xl ratios decreased (p<0.01; p<0.001) compared to the control group. Conclusion: C. laurifolius leaf extracts emerge as a promising anticancer candidate, hindering cell proliferation and inducing apoptosis in colon and breast cancer cells. The classification of bioactive molecules may facilitate further clinical therapeutic interventions targeting colon and breast cancer.Öğe Pimecrolimus protects neuron-like SH-SY5Y cells against anti-inflammatory and anti-oxidant effects of both microglial secretome and hydrogen peroxide(Wiley, 2024) Kocanci, Fatma Gonca; Erol, Azize Yasemin Goksu; Yildiz, Fatma; Eciroglu, HamiyetCalcineurin inhibitors have been found to exhibit a preventive role against neuroinflammation, which represents a crucial underlying mechanism in neurodegenerative diseases (ND). Additionally, they possess suppressive effects on the activation of apoptotic pathways, which constitute another mechanism underlying such diseases. Given that pimecrolimus, a calcineurin inhibitor, impedes the synthesis of pro-inflammatory cytokines, such as interleukin (IL)-2, IL-4, and IL-10, and influences apoptotic processes, it is noteworthy to test its potential neuroprotective properties. Thus, the objective of this investigation was to assess the potential protective effects of pimecrolimus against the degenerative consequences of both microglial secretomes and hydrogen peroxide (H2O2), an oxidant agent. The survival rates of HMC3 microglia cells, neuron-like differentiated SH-SY5Y (d-SH- SY5Y) cells, and their co-culture were determined using the 3-( 4,5-Dimethylthiazol- 2- yl)- 2,5- Diphenyltetrazolium Bromide (MTT) method. Furthermore, the levels of pro-inflammatory cytokines IL-1 beta and IL-6, and anti-inflammatory cytokine IL-10 were measured using ELISA kits, besides total antioxidant and oxidant capacities in conditioned media of cells. Additionally, the effect of pimecrolimus on neurite length in these cell groups was evaluated through morphological observations. This study revealed, for the first time, that pimecrolimus exerts preventive effects on neurodegenerative processes by virtue of its anti-inflammatory and -antioxidant activities. It holds promise as a potential treatment option for ND.Öğe Protective effect of Lumbricus rubellus Hoffmeister extract in experimental renal ischemia/reperfusion injury in the nephrectomy rats(Natl Inst Science Communication-Niscair, 2023) Oz, Semih; Yildiz, Fatma; Kabay, Sahin; Senturk, Hakan; Donmez, Dilek Burukoglu; Ozbayer, Cansu; Ustuner, Mehmet CengizAcute kidney injury (AKI), an immediate loss of renal function, leads to high mortality, and ischemia-reperfusion (I/R) injury is considered as one of the main causes of AKI. Inflammation and oxidative stress are known to play an important role in AKI. On the other hand, the earthworm extract, used in traditional medicine, is known to possess various biological and pharmacological activities viz. antiapoptotic, anticoagulative, fibrinolytic, anti-inflammatory, antioxidative stress, peripheral nerve regeneration, bone regeneration and wound healing. Hence, in this study, we investigated the protective effect of the earthworm Lumbricus rubellus Hoffmeister extract (LE) after nephrectomy, against oxidative stress occurring during renal ischemia/reperfusion (I/R) injury. A total of 10-12 weeks old Sprague Dawley male rats were divided into five groups (n=8). Group I (control), Group II (I/R), Group III (I/R + 10 mg/kg LE), Group IV (I/R + 20 mg/kg LE) and Group V (I/R + 40 mg/kg LE). All rats except in Gr. I were applied ischemia for 45 min and reperfusion for 24 h. At the end of the experiment, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) enzyme activities and malondialdehyde (MDA) levels were evaluated. In addition, kidney tissues were evaluated histologically. In results, the MDA and GPx level of the I/R group were found to be significantly higher than the control and LE groups. SOD activity of the control group did not differ when compared to LE groups and CAT levels were not significantly different between all groups. In addition, in Gr. III-V we observed nearly normal renal cortex and renal tubules. The present study, thus demonstrates that the extract of L. rubellus prevents renal I/R injury and induced biochemical and histological changes in the renal tissues in rats.Öğe Protective Effects of Lumbricus Extract on the Antioxidant System and Liver in an Experimentally Created Liver Ischemia Reperfusion Injury Model in Rats(Pleiades Publishing Inc, 2023) Oz, Semih; Yildiz, Fatma; Senturk, Hakan; Ustuner, Mehmet Cengiz; Donmez, Dilek Burukoglu; Kus, Gokhan; Ozbayer, CansuIn this experimental study, we investigated the effects of Lumbricus extract on biochemical and histological markers of liver IR injury model in rats. A total of 10-12-weeks old, 250-300 g Sprague Dawley male rats were divided into groups of five (n = 7). Group I (Sham), Group II (IR), Group III (IR + 10 mg/kg Lumbricus extract), Group IV (IR + 20 mg/kg Lumbricus extract), and Group V (IR + 40 mg/kg Lumbricus extract) were marked, respectively. Lumbricus extract was dissolved with saline and administered orally. All rats except in Group I were applied ischemia for 45 minutes and reperfusion for 24 hours. The data obtained at the end of the experiment were evaluated by histological and biochemical methods, where we investigated catalase (CAT) superoxide dismutase (SOD) enzyme activity and malondialdehyde (MDA) levels, as well as a histological examination of liver tissue samples. When MDA enzyme activity levels were compared with the sham and Lumbricus extract groups, it was found to be significantly higher than the IR group. SOD and CAT activity enzyme levels were found to be significantly lower. Our findings showed that Lumbricus extract could have a protective effect against experimentally induced IR injury in the liver by increasing antioxidant enzyme levels and decreasing lipid peroxidation and liver injury.Öğe The effect of controlled ovarian hyperstimulation on ovarian reserve via PTEN pathway(Bioscientifica Ltd, 2022) Sezginer, Perihan; Elmas, Cigdem; Yildiz, FatmaThis study was carried out to investigate whether repeated controlled ovarian hyperstimulation (COH) affects ovarian reserve. For this reason, we aimed to show possible changes in the expression of PTEN and FOXO3, which are involved in preserving the over-reserve, after applying the COH protocol methods. For this purpose, 18 young Wistar albino female rats (8 weeks old) were randomly assigned as group 1 (control), group 2, and group 3 as 6 subjects in each group. Experimental groups were treated with 10 IU/0.1 mL pregnant mare's serum gonadotropin and a COH protocol consisting of 10 IU/0.1 mL human chorionic gonadotropin injection after 48 h. This procedure was applied three and five times to group 2 and group 3, respectively. For the control groups, the same procedures were performed with 0.1 mL of 0.9% sodium chloride solution. At the end of the experiment, the ovarium tissues were placed in a 10% neutral formaldehyde solution for light microscopic examinations. In histological sections stained with hematoxylin and eosin, the number of ovarian follicles was determined using the physical dissector method. However, the expression of PTEN, FOXO3, and LH-R molecules was evaluated by immunohistochemical methods. As a result of our study, it was concluded that COH administration reduces the expression levels of PTEN and FOXO3 proteins and LH-R, which are among the essential components of the PIK3 intracellular signaling pathway and also increased the levels of hormones such as follicle-stimulating hormone, estradiol, and luteinizing hormone, which are over-reserve markers, and causes adverse effects on the histological structure, oocyte morphology, and number of ovaries. Lay summary Today, approximately 10-15% of couples experience fertility problems. However, assisted reproductive techniques help people with fertility problems to get pregnant. The main purpose of these techniques is to put the sperm and egg together outside the woman's body where the eggs are fertilized and then to return the fertilized eggs (embryos) to the womb. During a woman's menstrual cycle, several hormones influence the growth of the eggs. This process can be mimicked by using various medications. Medication is given to increase the number of eggs that develop. However, this method is not the same as normal ovulation. Therefore, in our study, we wanted to examine the effect that developing multiple follicles has on the number and quality of eggs remaining for the future.Öğe The Protective Effects of Geraniol Against Damage of Short Term Renal Ischemia-Reperfusion in Rats(Univ Sao Paulo, Conjunto Quimicas, 2023) Danis, Seren; Can, Senanur; Yildiz, Fatma; Yilmaz, Isil Tan; Canbek, Mediha; Yaylaci, Ayse OzmenIschemia/reperfusion (I/R) injury is one of the main causes of acute kidney injury. The pathological mechanisms underlying renal I/R injury are complex and remain uncertain. The protective effects of antioxidant properties of geraniol against renal ischemia reperfusion (I/R) damage were investigated in our study. 28 Wistar albino male rats were randomly selected and 4 groups of n = 7 were created. A right kidney nephrectomy surgery was conducted to all groups under anesthesia. 2 ml SF was given to Groups I and II, 50 mg/kg and 100 mg/ kg geraniol were administered intraperitoneally an hour before ischemia to Groups III and IV, respectively. Except for Group I, 45 minutes of ischemia and 4 hours of reperfusion were applied to the groups. At the end of the experiment, parameters related to oxidative stress and inflammation were determined by comparing kidney function, antioxidant enzyme activities and histological changes. Following comparison of BUN and CRE values with CAT and SOD values in tissue samples of Group I and Group II, an increase in Group II was observed and as a result I/R damage formation occurred. Values of geraniol-treated Group III and Group IV approximated to that of Group I, and that the 50 mg/kg geraniol dose proved more effective than 100 mg/kg geraniol.
