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    Cardioprotective effect of oleuropein in a cisplatin-induced cardiotoxicity model in rats
    (Springer, 2024) Gokcek, Ishak
    This study investigated the cardioprotective effect of oleuropein against cisplatin-induced cardiac damage in terms of inflammatory, oxidative stress and cardiac parameters. In this study, 40 female Wistar albino rats were divided into four groups: control, cisplatin, oleuropein and cisplatin+oleuropein. To establish the experimental model, oleuropein (200 mg/kg) was administered for 14 days and cisplatin (7 mg/kg) was administered as a single dose on the seventh day. Cisplatin increased MDA cardiac parameters (CK, CK-MB and cTnI) and inflammatory cytokines (TNF-alpha, IL-1 beta and IL-6) in cardiac tissue and decreased GSH, GSH-Px and catalase levels. On the other hand, oleuropein improved cardiac parameters and decreased inflammatory cytokine and oxidative stress levels in cardiac tissue.
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    Effect of exogenous Melatonin administration on Spermatogenesis in chronic unpredictable stress rat model
    (Univ Zulia, Facultad Ciencias Veterinarias, 2023) Gokcek, Ishak; Aydin, Leyla; Cellat, Mustafa; Yavas, Ilker; Kutlu, Tuncer
    This study investigated the hormonal, inflammatory, oxidant-antioxidant, and histopathological effects of exogenous Melatonin administration on Spermatogenesis in rats' chronic unpredictable stress model (CUSM). In the study, stress caused a decrease in follicle stimulating-hormone (FSH), luteinizing hormone (LH), Testosterone, Melatonin, Glutathione (GSH), Glutathione peroxidase (GSH-Px), catalase, interleukin 10 (IL-10) levels and motility, and an increase in Corticosterone, nuclear factor kappa beta (NF-kB), tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), abnormal sperm, dead/live sperm ratio and exogenous Melatonin reduced inflammatory cytokines and oxidative stress and improved spermatological parameters (P<0.05). Melatonin also partially corrected stress-induced changes in testicular morphology. As a result, using Melatonin in rats with CUSM may be effective in improving spermatological parameters through anti-inflammatory and antioxidant mechanisms.
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    Effect of Exogenous Melatonin Chronic Unpredictable Stress Model on Spermatogenesis in Rats
    (Wiley, 2022) Gokcek, Ishak; Aydin, Leyla; Cellat, Mustafa; Yavas, Ilker
    [Abstract Not Available]
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    Effects of thymol and carvacrol on sperm quality and oxidant/antioxidant balance in rats
    (Taylor & Francis Ltd, 2019) Guvenc, Mehmet; Cellat, Mustafa; Gokcek, Ishak; Yavas, Ilker; Ozsoy, Yule Yurdagul
    In this study, we have investigated the effects of different doses of thymol (T) and carvacrol (C) on sperm quality oxidative stress and antioxidant system. For this purpose, 49 rats were divided into seven groups (7 rats in each group): 1st Group (control); 2nd Group T-10 (thymol 10?mg/kg), 3rd Group T-20 (thymol 20?mg/kg), 4th Group C-10 (carvacrol 10?mg/kg), 5th Group C-20 (carvacrol 20?mg/kg), 6th Group T?+?C-10 (thymol 10?mg/kg?+?carvacrol 10?mg/kg) and 7th Group T?+?C-20 (thymol 20?mg/kg?+?carvacrol 20?mg/kg). The duration of the experiment was 10?weeks for all animals. During the study, sperm quality parameters (motility, concentration, abnormal spermatozoa and live?dead sperm ratio), biochemical parameters [malondialdehyde (MDA), reduced glutathione(GSH), glutathione peroxidase (GSH-Px), catalase (CAT), AST, ALT, GGT, urea and creatinine] were analysed, and histopathological examination was performed. The study results showed that monotherapies of thymol and carvacrol significantly decreased MDA levels in testicles, liver and kidney tissues compared to the control group (p?
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    Inula viscosa ameliorates acetic acid induced ulcerative colitis in rats
    (Taylor & Francis Ltd, 2023) Cellat, Mustafa; Tekeli, Ibrahim Ozan; Turk, Erdinc; Aydin, Tuba; Uyar, Ahmet; Isler, Cafer Tayer; Gokcek, Ishak
    Increased pro-inflammatory cytokines and oxidative stress contribute to the pathophysiology of ulcerative colitis (UC). Inula viscosa is a plant with antioxidant and anti-inflammatory properties. We investigated the effect of an ethanolic extract of I. viscosa on an experimental UC model created using acetic acid. Rats were divided into four groups of eight: group 1, control; group 2, 3% acetic acid group; group 3, 100 mg/kg sulfasalazine + 3% acetic acid group; group 4, 400 mg/kg I. viscosa + 3% acetic acid. I. viscosa and sulfasalazine were administered by oral gavage and 3% acetic acid was administered per rectum. We found that I. viscosa treatment decreased colon malondialdehyde, tumor necrosis factor-alpha, interleukin-1 beta and nuclear factor kappa B levels; it increased reduced glutathione, nuclear factor erythroid 2-related factor 2, heme oxygenase-1 and kelch-like ECH-associated protein 1 levels and glutathione peroxidase enzyme activity. Group 1 colon exhibited normal histological structure. Slight inflammatory cell infiltration and edema and insignificant slight erosion in crypts were detected in colon tissues of group 4. We found that I. viscosa reduced oxidative stress and inflammation, which was protective against UC by inducing the Nrf-2/Keap-1/HO-1 pathway in the colon.
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    Nobiletin attenuates acetaminophen-induced hepatorenal toxicity in rats
    (Wiley, 2020) Guvenc, Mehmet; Cellat, Mustafa; Gokcek, Ishak; Ozkan, Huseyin; Arkali, Gozde; Yakan, Akin; Ozsoy, Sule Yurdagul
    The study aimed to examine the effects of nobiletin on the toxicity model induced with acetaminophen (APAP). For this purpose, 24 adult male rats were equally divided into four groups. The groups were the control group (group 1); dimethyl sulfoxide only, the APAP group (group 2) received a single dose of APAP 1000 mg/kg on the 10th day of experiment; the Nobiletin group (group 3), nobiletin (10 mg/kg) for 10 days; and the APAP + Nobiletin group (group 4), nobiletin (10 mg/kg) for 10 days with a single dose of APAP (1000 mg/kg) administered on the 10th day and the experiment ended after 48 hours. At the end of the study, a significant increase in malondialdehyde, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels and a significant decrease in glutathione levels, glutathione peroxidase activities and nuclear factor erythroid-derived 2-like 2 (Nrf-2) and heme oxygenase-1 (HO-1) expressions were observed with APAP application in liver and kidney tissues. Serum aspartate transaminase (AST), alanine transaminase (ALT), urea, and creatinine levels were also significantly increased in the APAP group. However, nobiletin treatment in group 4 reversed oxidative stress and inflammatory and histopathological signs caused by APAP. It is concluded that nobiletin may be a beneficial substance that confers hepatorenal protection to APAP-induced toxicity via antioxidant and anti-inflammatory mechanisms.
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    Nobiletin Protects from Renal Ischemia-Reperfusion Injury in Rats by Suppressing Inflammatory Cytokines and Regulating iNOS-eNOS Expressions
    (Springer/Plenum Publishers, 2020) Guvenc, Mehmet; Cellat, Mustafa; Uyar, Ahmet; Ozkan, Hueseyin; Gokcek, Ishak; Isler, Cafer Tayer; Yakan, Akin
    Ischemia-reperfusion injury is an organ failure caused by hypoxia and reperfusion, which is closely associated with oxidative stress and inflammation. In this study, we investigated whether nobiletin had protective effects on inflammatory parameters, oxidative damage, iNOS-eNOS expressions, and histopathological structure of renal tissue in rats with renal ischemia-reperfusion injury. For this purpose, 24 rats were divided into 4 groups: group 1 (Control), group 2 (Ischemia-Reperfusion-IR), group 3 (Nobiletin-10 mg/kg p.o.), group 4 (Nobiletin + IR). The study was continued for 7 days. At the end of the study, urea (p < 0.05), creatine (p < 0.05), MDA (p < 0.001), TNF-alpha (p < 0.001), IL-1 beta (p < 0.05), and IL-6 (p < 0.001) levels increased in the IR group; however, a significant decrease occurred in group 4 (Nobiletin + IR) and it reached the control group levels. In the IR group, GSH (p < 0.01) levels, and GSH.Px (p < 0.01) and CAT (p < 0.05) activities decreased whereas they increased significantly in group 4 (Nobiletin + IR) and reached the same levels as the control group. In histopathological analyses, destruction and increased iNOS-eNOS expressions in the IR group showed a significant decrease in group 4 (Nobiletin + IR). As a result, the application of nobiletin has shown that it has protective effects by reducing kidney damage caused by IR injury.
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    Protective effect of oleuropein on ketamine-induced cardiotoxicity in rats
    (Springer, 2020) Comez, Mehmet Selim; Cellat, Mustafa; Ozkan, Huseyin; Borazan, Yakup; Aydin, Tuba; Gokcek, Ishak; Turk, Erdinc
    The antioxidant and cardioprotective effects of oleuropein have been reported in several studies; however, its effect on ketamine cardiotoxicity has not been known yet. The aim of this study was to investigate the effects of oleuropein in ketamine-induced cardiotoxicity model in rats. A total of 28 male Wistar Albino rats were included in the study and they were randomly divided into four groups, each having seven rats. Group 1 (control): rats were given 1 mL of DMSO by oral gavage method for 7 days. Group 2 (ketamine): on the seventh day of the study, 60 mg/kg ketamine was administered intraperitoneally. Then, 60 mg/kg ketamine was administered intraperitoneally every 10 min for 3 h. Group 3 (oleuropein): rats were given 200 mg/kg/day oleuropein by oral gavage method for 7 days. Group 4 (oleuropein + ketamine): rats were given 1 x 200 mg/kg oleuropein by oral gavage method for 7 days. Furthermore, 60 mg/kg ketamine was administered intraperitoneally on the seventh day of the experiment. Then, 60 mg/kg ketamine was administered intraperitoneally every 10 min for 3 h. Serum cardiac marker (TnI, CK-MB and CK) levels were measured. Histopathological analysis was performed on a portion of the cardiac tissue. Cardiac tissue oxidative stress and antioxidant markers (MDA, GSH, GSH.Px and CAT), TNF-alpha, IL-6, NF-kappa B, COX-2 and Nrf-2 gene expressions, and protein conversion levels of related genes were determined. Data obtained showed that ketamine administration increased MDA (p < 0.001), TNF-alpha (p < 0.01), IL-6 (p < 0.01), COX-2 (p < 0.001) and NF-kappa B (p < 0.001) levels, as well as serum TnI (p < 0.001), CK-MB (p < 0.001) and CK (p < 0.01) levels whereas decreased GSH (p < 0.05) and Nrf-2 (p < 0.05) levels, as well as GSH-Px (p < 0.001) and CAT (p < 0.05) enzyme activities. Oleuropein administration was observed to decrease MDA, TNF-alpha, IL-6, COX-2, NF-kappa B, TnI, CK-MB and CK levels close to the control group and to increase GSH levels and GSH-Px and CAT enzyme activities close to the control group. This study showed that oleuropein administration reversed the increased oxidative stress and inflammation as a result of the use of ketamine and had protective effects on the heart.
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    Protective Effects of Tyrosol Against DSS-Induced Ulcerative Colitis in Rats
    (Springer/Plenum Publishers, 2019) Guvenc, Mehmet; Cellat, Mustafa; Ozkan, Huseyin; Tekeli, Ibrahim Ozan; Uyar, Ahmet; Gokcek, Ishak; Isler, Cafer Tayer
    In this study, the effects of tyrosol were investigated in DSS-induced experimental ulcerative colitis model. For this purpose, rats were divided into five groups of seven rats in each: control group, colitis group (DSS-4%), tyrosol group (tyrosol 20 mg/kg), sulfasalazine (sulfasalazine+DSS 100 mg/kg), and treatment group (tyrosol+DSS 20 mg/kg). In the study, the active substances were administered to all animals for a period of 21 days. At the end of the study, malondialdehyde (MDA) levels increased (p < 0.001); GSH level (p < 0.05) along with GSH.Px (p < 0.01) and CAT (p < 0.001) activities decreased in the DSS-induced colitis group. However, with the administration of tyrosol, MDA and GSH levels along with GSH.Px and CAT activities came to the same levels as the control group. In the colitis group, an increase occurred in IL-6, COX-2, and NF-kappa B parameters, which created a significant difference compared to the control group (p < 0.001). Similarly, TNF-alpha levels also significantly increased with the administration of DSS (p < 0.05) which created a significant difference compared to the control group, while there was no difference among the other groups. As for the Nrf-2 data, it decreased with the administration of DSS which created a significant difference compared to the control group (p < 0.05), while there was no difference in other groups. In the colitis-induced group, IL-6, COX-2, and NF-kappa B gene expression levels also similarly increased but returned to the normal levels with the administration of tyrosol. In the histopathological scoring, the negativity that increased with the administration of DSS returned to the normal levels with the administration of tyrosol+DSS. In conclusion, according to the data obtained, tyrosol fixed the destruction picture in the DSS-induced colitis model, giving rise to thought that it has a protective effect.
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    Protective Effects of Tyrosol Against DSS-Induced Ulcerative Colitis in Rats (vol 42, pg 1680, 2019)
    (Springer/Plenum Publishers, 2019) Guvenc, Mehmet; Cellat, Mustafa; Ozkan, Huseyin; Tekeli, Ibrahim Ozan; Uyar, Ahmet; Gokcek, Ishak; Isler, Cafer Tayer
    [Abstract Not Available]
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    Tyrosol improves ovalbumin (OVA)-induced asthma in rat model through prevention of airway inflammation
    (Springer, 2021) Cellat, Mustafa; Kuzu, Muslum; Isler, Cafer Tayer; Etyemez, Muhammed; Dikmen, Nursel; Uyar, Ahmet; Gokcek, Ishak
    Asthma is an inflammatory disease that affects many people around the world, especially persons at paediatric age group. The effectiveness of tyrosol, a natural phenolic compound, was examined in the asthma model induced by ovalbumin (OVA). For this purpose, four groups, each consisting of eight rats, were arranged. For 21 days, physiological saline solution was treated to the control group and OVA was treated to the groups of OVA, OVA + dexamethasone (Dexa) and OVA + tyrosol groups, intraperitoneally and through inhalation. Additionally, 0.25 mg/kg Dexa was treated to the OVA + Dexa group and 20 mg/kg tyrosol to the OVA + tyrosol group by oral gavage. Serum, blood, bronchoalveolar lavage fluid (BALF) and lung tissues of the rats were examined. It was observed that MDA level decreased, GSH level and GPx activity increased, and there was no change in CAT activity in lung tissues of the tyrosol treatment groups. It was also observed that NF-kappa B, TNF-alpha, IL-4, IL-5, IL-13, IFN-gamma and IgE levels decreased compared to the OVA group in lung tissue and serum samples except for serum NF-kappa B and IL-4. However, no effect on IL-1 beta level was observed. In addition, it was determined that tyrosol treatment increased the IL-10 level on both tissue samples. The results of the histopathological investigation of lung tissue showed that tyrosol significantly ameliorated OVA-induced histopathological lesions. Additionally, PAS staining showed that mucus hypersecretion was significantly reduced with the use of tyrosol. In addition, it was determined that the number of eosinophils decreased significantly in blood and BALF samples. The obtained results showed that tyrosol possessed antioxidant and anti-inflammatory features on OVA-induced rats and preserved tissue architecture.
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    Tyrosol improves ovalbumin (OVA)-induced asthma in rat model through prevention of airway inflammation (Jul, 10.1007/s00210-021-02117-y, 2021)
    (Springer, 2021) Cellat, Mustafa; Kuzu, Muslum; Isler, Cafer Tayer; Etyemez, Muhammed; Dikmen, Nursel; Uyar, Ahmet; Gokcek, Ishak
    [Abstract Not Available]
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    Tyrosol prevents AlCl3 induced male reproductive damage by suppressing apoptosis and activating the Nrf-2/HO-1 pathway
    (Wiley, 2020) Guvenc, Mehmet; Cellat, Mustafa; Gokcek, Ishak; Arkali, Gozde; Uyar, Ahmet; Tekeli, Ibrahim Ozan; Yavas, Ilker
    Aluminium is a ubiquitous element that occurs naturally in the soil making human exposure to it is unavoidable. Tyrosol is present in olive oil and is known to have antioxidant effects. Therefore, the present study explores the toxic effects of aluminium chloride (AlCl3) and evaluates the possible protection by tyrosol in male rats. Testicular injury was induced by the administration of AlCl3 (34 mg kg(-1) day(-1)). Rats were treated with either tyrosol (20 mg kg(-1) day(-1)) or AlCl3 (34 mg kg(-1) day(-1)). The experiment lasted for 10 weeks. Biochemical, histopathological and protein expression profiles were determined to decipher the role of tyrosol in protecting the cellular damage. Further, histomorphometric analyses of testes showed deranged architecture along with other noted abnormalities. AlCl3 group rats' testes showed decreased GSH levels, CAT activities, Nrf-2, HO-1, bcl-2 expressions and sperm motility whereas increased caspase-3 expressions, MDA levels, abnormal and dead/live sperm ratio. However, tyrosol treatment attenuated these changes. The present results demonstrate the beneficial role of tyrosol treatment in AlCl3 induced testicular toxicity alterations of rat.