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- ArticleAçık Erişim2020The effect of desloratadine on ischemia reperfusion induced oxidative and inflammatory renal injury in rats
Kocaturk, Huseyin; Bedir, Fevzi; Altay, Mehmet Sefa; Bakan, Ebubekir; Suleyman, Bahadir; Yazici, Gulce Naz; Sunar, Mukadder; Suleyman, Zeynep; Suleyman, Halis
Purpose: To examine the effect of desloratadine on kidney ischemia-reperfusion (I/R) injury in albino Wistar male rats using biochemical and histopathological methods. Methods: The treated with ischemia–reperfusion + 5 mg/kg desloratadine (IRD) group (n–6) was given 5 mg/kg desloratadine by gavage orally, and applied renal ischemia-reperfusion (BIR) group (n–6) and control (SG) group undergoing Sham operation (n–6) rats were given distilled water as solvent one hour before ketamine anesthesia. During the anesthesia period, ischemia was induced for 2 h unilaterally in the left kidney of all rats followed by reperfusion for 6 h. The kidneys of the SG group had sham operation without any intervention. Results: Our biochemical test results showed that malondialdehyde (MDA), nuclear factor kappa (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin one beta (IL-1β), creatinine, and blood urea nitrogen (BUN) levels were significantly increased in the BIR group compared to the healthy control and IRD groups treated with desloratadine. Histopathological results were revealed tubular dilatation, tubular necrosis, loss of brushy margins, cast formation, and apoptotic bodies in tubular epithelial cells in the BIR group. There were no histopathological findings except for the swelling of tubule epithelial cells and the accumulation of proteinous material in some tubule lumens in renal tissue of desloratadine-treated rats. Conclusions: Experimental results suggested that desloratadine may be useful in the treatment of renal I/R injury.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2020Comparative study of the protective effects of adenosine triphosphate and resveratrol against amiodarone-induced potential liver damage and dysfunction in rats
Karadogan, Muhammed Talha; Yavuzer, Bulent; Gursul, Cebrail; Huseynova, Gulbaniz; Yazici, Gulce Naz; Gulaboglu, Mine; Yilmaz, Furkan; Mendil, Ali Sefa; Suleyman, Halis
Background. Amiodarone is the most commonly used class III antiarrhythmic drug with antiarrhythmic and vasodilator properties. Adenosine triphosphate (ATP) serves as a crucial source of intracellular energy, while resveratrol is known for its potent antioxidant activity. Objectives. This study aimed to biochemically, histopathologically and immunohistochemically evaluate the effects of ATP, resveratrol and their combination on potential liver damage and dysfunction induced by amiodarone in rats. Materials and methods. The rats were divided into 6 groups: healthy control (HG), amiodarone alone (ADG), amiodarone + ATP at 2 mg/kg (AAG-2), amiodarone + ATP at 5 mg/kg (AAG-5), resveratrol + amiodarone (RAG), and resveratrol + amiodarone + ATP at 2 mg/kg (RAA-2). Amiodarone (50 mg/kg, orally), ATP (2 mg/kg and 5 mg/kg, intraperitoneally) and resveratrol (25 mg/kg, orally) were administered once daily for 14 days. Following treatment, liver tissues were excised for biochemical analysis. Oxidative stress was assessed by measuring malondialdehyde (MDA) levels, while antioxidant status was evaluated through total glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. To assess liver function, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured in serum samples collected from the animals’ tail veins. In addition, liver tissues were subjected to histopathological and immunohistochemical examination to evaluate structural and molecular changes associated with treatment. Results. Amiodarone administration led to a significant increase in oxidative stress markers and a reduction in antioxidant levels in rat liver tissue. Additionally, serum levels of ALT and AST were elevated, indicating liver dysfunction. Histopathological and immunohistochemical analyses revealed severe (grade 3) oxidative damage in the liver tissue. All biochemical parameters in the 5 mg/kg ATP and resveratrol + 2 mg/kg ATP treatment groups were comparable to those observed in the HG group. Histopathological and immunohistochemical evaluations showed a reduction in liver damage severity to grade 2 in the groups treated with ATP (2 mg/kg) and resveratrol alone, and to grade 1 in the groups receiving ATP (5 mg/kg) or the combination of resveratrol + ATP (2 mg/kg). Conclusions. The results of the present study suggest that adjusting the ATP dosage or using a combination of ATP and resveratrol may be effective strategies for minimizing amiodarone-induced liver damage.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2020Effects of anakinra on the small intestine mucositis induced by methotrexate in rats
Ozcicek, Fatih; Kara, Ali Veysel; Akbas, Emin Murat; Kurt, Nezahat; Yazici, Gulce Naz; Cankaya, Murat; Mammadov, Renad; Ozcicek, Adalet; Suleyman, Halis
Intestinal mucositis is an important problem in the patients receiving cancer treatment. We aimed to investigate the effect of anakinra, which is a well known anti-oxidant and anti-inflammatory agent, on methotrexate-induced small intestine mucositis in rats. Forty rats were divided into 4 groups with 10 in each group. The healthy group (HG) and the methotrexate group (MTXG) were given distilled water, while the methotrexate + anakinra 50 (MTX+ANA50) and the methotrexate + anakinra 100 (MTX+ANA100) groups were intraperitoneally administered 50 and 100 mg/kg of anakinra. After one hour, the MTXG, MTX+ANA50 and MTX+ANA100 groups were given oral methotrexate at a dose of 5 mg/kg. This procedure was repeated once a day for 7 days. After the rats had been sacrificed, the small intestine tissue of rats were removed for the assesment of biochemical markers, histopathological evaluation and gene expression analyze. Statistical analyses of the data were performed using one-way ANOVA. Malondialdehyde (MDA), myeloperoxidase (MPO) and interleukin-6 (IL-6) levels were significantly higher, whereas total glutathione (tGSH) levels were significantly lower in MTXG (P<0.001) compared to other groups. MTX also increased IL-1β and TNF-α gene expression levels in MTXG (P<0.001). Inflammatory cell infiltration and damage to the villus were observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the MTX+ANA100 group. A dose of 100 mg/kg of anakinra prevented the increase of the biochemical markers and gene expression levels better than a dose of 50 mg/kg. Intestinal mucositis caused by MTX may be preventible by co-administered anakinra.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2020Effects of adenosine triphosphate on methanol-induced experimental optic nerve damage in rats: biochemical and histopathological evaluation
Icel, Erel; Suleyman, Halis; Yazici, Gulce Naz; Bakan, Nuri; Sunar, Mukadder
Purpose: Acute methanol exposure leads to systemic intoxication and toxic optic neuropathy. In this experimental study, we aimed to determine the protective effects of intravenous administration of ATP in methanol-induced optic neuropathy. Materials and methods: A total of 18 male albino Wistar rats weighing between 267 and 282 g were used for the experiment. The animals were divided into three groups as healthy control (HC), methanol (M), and methanol + ATP (M-ATP) groups. Distilled water was given to the healthy control group (n = 6) as the solvent, while 20% methanol was administered orally to the rats in M (n = 6) and M-ATP (n = 6) groups at a dose of 3 g/kg. Four hours after the administration of 20% methanol orally to the M-ATP group, ATP was injected intraperitoneally at a dose of 4 mg/kg. Eight hours after ATP injection, the animals were sacrificed by high-dose (50 mg/kg) thiopental anaesthesia and biochemical and histopathological examinations were performed on the removed optic nerve tissues. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS) and total anti-oxidant status (TAS) were analysed with biochemical tests. Results: MDA, TOS and OSI were significantly higher and tGSH and TAS levels were significantly lower in methanol administered group compared with the healthy controls or M-ATP group (p: 0.001). There was not any significant difference between healthy controls and M-ATP group regarding the oxidative stress parameters. There was a significant destruction and increase in thickness and astrocyte numbers and edema-vacuolization in methanol administered group compared with the healthy controls or M-ATP group (p: 0.001). Conclusion: Intravenous ATP administration had a significant positive effect on the oxidative stress parameters and optic nerve structure in methanol-intoxicated rats. Antioxidant therapies should be considered in future studies as a possible therapy for methanol-induced toxic optic neuropathy.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2020Effects of adenosine triphosphate on vandetanib induced skin damage in rats
Akagunduz, Baran; Ozcicek, Fatih; Kara, Ali Veysel; Guven, Deniz Can; Yazici, Gulce Naz; Çoban, Abdulkadir; Suleyman, Bahadır; Mammadov, Renad; Suleyman, Halis
Purpose: Vandetanib is a wide spectrum tyrosine kinase inhibitor used for the treatment of metastatic medullary thyroid cancer (MTC) and various other cancer types. Although it is usually well-tolerated ıt has been linked to a variety of severe dermatologic reactions. Our study aimed was to investigate adenosine 5′-triphosphate (ATP) on vandetanib-induced skin damage. Materials and methods: A total number of 18 rats were divided into three equal groups as vandetanib group (VDB), vandetanib plus ATP group (VAT), and healthy group (HG); 25 mg/kg ATP was injected intraperitoneally (ip) to the VAT group. Normal saline was given to the HG and VDB groups as solvent via intraperitoneally. One hour later, 25 mg/kg vandetanib was applied orally via an orogastric catheter in the VAT and VDB groups. This procedure was repeated once daily for 4 weeks. After that period, all animals were sacrificed and their skin tissues removed. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), total antioxidant status (TAS) levels in rats’ skin tissues were evaluated with histopathological analyses. Results: MDA and TOS levels measured higher in the VDB group compared to the VAT and HG groups (p < 0.001). tGSH and TAS levels of the VDB group measured lower than the VAT and HG groups (p < 0.001). The structure and morphology of skin tissue were normal in the control group. In the VDB group, skin tissue damage with thinner epitelium, ruptured and degenerated hair follicles, abnormal accumulation of abnormal keratin on the epithelium and oedematous areas in the dermis was observed. In the VAT group, these findings were significantly improved. Conclusion: We demonstrated that adenosine triphosphate can prevent vandetanib-induced skin toxicity in rats for the first time. The promising results denote that further studies testing this agent in other animal models and in humans are warranted.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2020An experimental study on the use of lycopene to prevent infertility due to acute oxidative ovarian damage caused by a single high dose of methotrexate
Turkler, Can; Onat, Taylan; Yildirim, Engin; Kaplan, Selcuk; Yazici, Gulce Naz; Mammadov, Renad; Sunar, Mukadder
Background. Methotrexate (MTX) is an antineoplastic agent, which increases the level of reactive oxygen species (ROS) and decreases the level of antioxidants. Lycopene, is a potent antioxidant, which is used because of its protective effect against tissue damage. Objectives. The aim of this study was to determine the effect of lycopene on ovarian MTX-induced injury in rats. Material and methods. Rats (n = 36) were randomly divided into 3 equal groups: a group with MTX only (MG, n = 12), a group with lycopene and MTX (LMG, n = 12), and a healthy control group (HCG, n = 12). Then, malondialdehyde (MDA), myeloperoxidase (MPO) and total glutathione (tGSH) levels and histopathological findings were examined in the ovaries of rats. Apart from the histopathological and biochemical evaluation, the reproductive performance of the experimental groups was also examined. Results. Our study demonstrated that, in ovarian tissues of rats administered MTX, there was a decrease in the levels of tGSH, while MDA and MPO were increased, but it is observed that these ratios are reversed in the LMG (p < 0.05). It also has been proven that a single, high-dose use of MTX causes infertility in female rats, prolongs the gestation period and reduces the number of offspring. Conclusions. Lycopene pretreatment ameliorates the MTX induced ovarian injury and infertility in rats through its antioxidative activities.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2019Effects of pycnogenol on ischemia/reperfusion-induced inflammatory and oxidative brain injury in rats
Ozoner, Baris; Yuceli, Sahin; Aydin, Seckin; Yazici, Gulce Naz; Sunar, Mukadder; Arslan, Yusuf Kemal; Coban, Taha Abdulkadir; Suleyman, Halis
Background: Ischemia/reperfusion (I/R) injury results from the onset of re-circulation following a perfusion deterioration period in the tissues, resulting in more damage than that caused by perfusion deterioration. This study aimed to determine the effects of pycnogenol on I/R injury in rat brain tissues. Methods: Eighteen albino Wistar rats were divided into three groups: I/R injury (IR, n = 6) group; I/R injury + pycnogenol (IR + P, n = 6) group; and sham group (SG, n = 6). After 30 min of transient ischemia, 24 h of reperfusion was achieved in the IR and IR + P groups. Surgical dissection, except for transient ischemia, was performed in SG. Next, histopathological and biochemical investigations were performed on brain tissues. Malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GPO) were analyzed as oxidative stress markers; IL-1β and TNF-α were analyzed as inflammatory stress markers in biochemical tests. Results: Histopathological examination revealed normal morphology in SG and diffuse cortex damage with edema, vasopathology, and inflammatory cell infiltration in the IR group. The IR + P group showed less cortex damage, edema, and vasopathology than the IR group. The MDA, IL-1β, and TNF-α levels were significantly higher in the IR group than those in the SG group. The values of same markers for the IR + P group were significantly lower than the IR group. The GSH and GPO levels were significantly decreased with IR damage, but PYC treatment showed significant improvement in the levels. Conclusion: This study showed that the administration of pycnogenol ameliorated brain damage after I/R injury by reducing oxidative and inflammatory damage in the rat brain.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2019Functional profiling identifies determinants of arsenic trioxide cellular toxicity
Sobh, Amin; Loguinov, Alex; Yazici, Gulce Naz; Zeidan, Rola S.; Tagmount, Abderrahmane; Hejazi, Nima S.; Hubbard, Alan E.; Zhang, Luoping; Vulpe, Chris D.
Arsenic exposure is a worldwide health concern associated with an increased risk of skin, lung, and bladder cancer but arsenic trioxide (AsIII) is also an effective chemotherapeutic agent. The current use of AsIII in chemotherapy is limited to acute promyelocytic leukemia (APL). However, AsIII was suggested as a potential therapy for other cancer types including chronic myeloid leukemia (CML), especially when combined with other drugs. Here, we carried out a genome-wide CRISPR-based approach to identify modulators of AsIII toxicity in K562, a human CML cell line. We found that disruption of KEAP1, the inhibitory partner of the key antioxidant transcription factor Nrf2, or TXNDC17, a thioredoxin-like protein, markedly increased AsIII tolerance. Loss of the water channel AQP3, the zinc transporter ZNT1 and its regulator MTF1 also enhanced tolerance to AsIII whereas loss of the multidrug resistance protein ABCC1 increased sensitivity to AsIII. Remarkably, disruption of any of multiple genes, EEFSEC, SECISBP2, SEPHS2, SEPSECS, and PSTK, encoding proteins involved in selenocysteine metabolism increased resistance to AsIII. Our data suggest a model in which an intracellular interaction between selenium and AsIII may impact intracellular AsIII levels and toxicity. Together this work revealed a suite of cellular components/processes which modulate the toxicity of AsIII in CML cells. Targeting such processes simultaneously with AsIII treatment could potentiate AsIII in CML therapy.
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