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Öğe The effect of tyrosol on diclofenac sodium-induced acute nephrotoxicity in rats(Wiley, 2024) Comez, Mehmet; Cellat, Mustafa; Kuzu, Muesluem; Uyar, Ahmet; Turk, Erdinc; Kaya, Yusuf Selim; Etyemez, MuhammedAlthough diclofenac (DCF) is a nonsteroidal anti-inflammatory drug that is considered safe, its chronic use and overdose may show some toxic effects. The protective effect of tyrosol (Tyr) pretreatment against DCF-induced renal damage was investigated in this study. The 32 rats used in the study were randomly divided into four groups of eight rats each. According to the data obtained, it was determined that creatinine, urea, and blood urea nitrogen (BUN) levels increased in serum samples of the DCF group. Besides, the levels of reduced glutathione (GSH) and glutathione peroxidase (GPx) activity decreased and the malondialdehyde (MDA) level increased in the kidney tissue. However, no change was observed in catalase (CAT) activity. Cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-kappa B), and tumor necrosis factor-alpha (Tnf-alpha) levels increased and nuclear factor erythroid 2-related factor 2 (Nrf-2) levels decreased. No change was detected in the level of interleukin 1 beta (IL-1 beta). When the DCF+Tyr group and the DCF group were compared, it was assessed that Tyr had a curative effect on all biochemical parameters. Also, kidney damages, such as degeneration and necrosis of tubular epithelium and congestion of veins, were obviated by treatment with tyrosol in histopathological examinations. It was determined that Tyr pretreatment provided a protective effect against nephrotoxicity induced by DCF with its anti-inflammatory and antioxidant properties.Öğe Effect of Xylazine on Pharmacokinetics and Physiological Efficacy of Intravenous Carprofen in Castrated Goats Kids(Mdpi, 2023) Uney, Kamil; Yuksel, Murat; Corum, Duygu Durna; Coskun, Devran; Turk, Erdinc; Dingil, Hasan Basri; Corum, OrhanCarprofen can be used in the castration process of male goats due to its low side effects, long elimination half-life, and long-term effect. However, no studies were found on the pharmacokinetics and physiological efficacy of carprofen when employed for castration in male goats. The aim of this study was to determine the effect of xylazine (0.05 mg/kg, intramuscular) on the pharmacokinetics and physiological efficacy following intravenous administration of carprofen (4 mg/kg, intravenous) in male goat kids castrated using the burdizzo method. Thirty male Kilis goat kids (5-6 months and 18-30 kg of body weight) were randomly assigned to five groups (n = 6) as follows: healthy control (HC), castration control (CAST), castration+carprofen (CAST+CRP), castration+xylazine (CAST+XYL), and castration+xylazine+carprofen (CAST+XYL+CRP). Plasma concentrations of carprofen were analyzed via a non-compartmental method. Physiological parameters including serum cortisol, scrotal temperature, rectal temperature, and scrotal circumference were determined. Xylazine caused a decrease in the volume of distribution and clearance and an increase in the area under the curve of carprofen in CAST+XYL+CRP group (p < 0.05). The mean cortisol concentrations in CAST+CRP and CAST+XYL remained lower compared to CAST (p < 0.05). The mean cortisol concentrations in CAST+XYL+CRP were lower than in CAST+CRP and CAST+XYL (p < 0.05). In addition, the effect of carprofen administration alone on reducing the initial cortisol response to castration was observed from 6 to 48 h, while in combination with xylazine, it was observed immediately up to 48 h. No treatment differences were observed in rectal temperature, scrotal temperature, and scrotal circumference (p > 0.05). Xylazine caused an increase in plasma concentration and a decrease in clearance of carprofen after co-administration. However, when the effect of the combined administration of carprofen with xylazine on cortisol is evaluated, their combined use in castration process may be beneficial.Öğe 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, IshakIncreased 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.Öğe Pharmacokinetics of letrozole and effects of its increasing doses on gonadotropins in ewes during the breeding season(Wiley, 2024) Kivrak, Mehmet Bugra; Corum, Orhan; Yuksel, Murat; Turk, Erdinc; Corum, Duygu Durna; Tekeli, Ibrahim Ozan; Uney, KamilLetrozole is a non-steroidal, third-generation aromatase inhibitor used in humans. Although letrozole is not approved for use in animals, it is used off-label in cases of synchronization and infertility. The aim of this study was to determine the pharmacokinetics of letrozole after a single intravenous administration at three different doses in ewes during the breeding season and its effect on gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) at the beginning of proestrus. The study was carried out on 24 healthy Merino ewes. Ewes were randomly divided into four groups (n = 6) as control, 0.5, 1, and 2 mg/kg. Plasma concentrations of letrozole were measured using HPLC-UV and were analyzed by non-compartmental analysis. LH and FSH concentrations were measured with a commercial ELISA kit. The terminal elimination half-life (t(1/2 lambda z)) was significantly prolonged from 11.82 to 18.44 h in parallel with the dose increase. The dose-normalized area under the concentration-time curve (AUC) increased, and total body clearance (Cl-T) decreased at the 1 and 2 mg/kg doses (0.05 L/h/kg) compared with the 0.5 mg/kg dose (0.08 L/h/kg). There were no differences in the volume of distribution at steady-state and initial (C-0.083h) plasma concentration values between dose groups. The decreased ClT, prolonged t(1/2 lambda z), and increased AUC at increasing doses showed the nonlinear kinetic behavior of letrozole. Letrozole significantly reduced LH concentration without affecting FSH concentration at all doses. As a result, letrozole has the potential to be used in synchronization methods and manipulation of the follicular waves due to its effect on LH secretion.Öğe The protective effect of esculetin against aluminium chloride-induced reproductive toxicity in rats(Wiley, 2021) Turk, Erdinc; Ozan Tekeli, Ibrahim; Ozkan, Huseyin; Uyar, Ahmet; Cellat, Mustafa; Kuzu, Muslum; Yavas, IlkerOne of the prominent health problems caused by Aluminium was the decrease in male fertility rates. In the study, the protective effect of Esculetin (ESC) against the reproductive toxicity induced by Aluminium chloride (AlCl3) was investigated. For this purpose, AlCl3 was administrated to Wistar Albino rats at a dose of 34 mg/kg and ESC was administrated at a dose of 50 mg/kg for 70 days. It was determined that AlCl3 treatment reduced sperm motility and concentration, increased dead/live rate and abnormal sperm rate. It decreased serum testosterone level, and co-treatment of ESC significantly regulated these values. In the AlCl3-treated group, MDA level increased and GSH level, GPx and CAT activities decreased compared with those of the control group. However, co-treatment of ESC showed an amelioratory effect on the values except for CAT activity. It was observed that the expression level of NRF-2 increased in the ESC and AlCl3 + ESC groups, and NF-kappa B increased in the AlCl3 group with the control group. It was determined that Caspase-3 expression decreased, and Bcl-2 expression increased in AlCl3 + ESC group compared to AlCl3 group. It was also determined that AlCl3-induced tissue injury was significantly prevented by ESC co-treatment.Öğe Protective effect of morin on doxorubicin-induced hepatorenal toxicity in rats(Elsevier Ireland Ltd, 2019) Kuzu, Muslum; Yildirim, Serkan; Kandemir, Fatih Mehmet; Kucukler, Sefa; Caglayan, Cuneyt; Turk, Erdinc; Dortbudak, Muhammet BahaeddinAlthough Doxorubicin (DOX) is a widespread drug used in the treatment of cancer, its clinical use is restricted due to its common side effects. In addition, administrating DOX with an antioxidant has recently become a new strategy in preventing the side effects of DOX. The protective effects of morin, a natural flavonoid, against DOX-induced liver and kidney damage in rats were investigated biochemically, immunohistochemically and histopathologically in this study. The experimental procedure was planned as 10 days, and 5 groups consisting of seven rats were formed. Morin was given orally to rats at a dose of 50 and 100 mg/kg for 10 days and DOX was given a single dose of 40 mg/kg intraperitoneally on day 8. In order to determine the protective effect of morin against oxidative stress caused by DOX, reduced glutathione (GSH) and malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzyme activities were measured in liver and kidney tissues. Liver and kidney tissue damage were determined both histopathologically and by serum alanine transaminase (ALT), aspartate transaminase (AST), urea and creatinine analysis. In order to determine the effect of DOX-induced inflammation and against the effect of morin, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and nuclear factor kappa B (NF-kappa B) levels were determined in both tissues. Liver and kidney B-cell lymphoma-2 (Bcl-2) levels were determined biochemically. In addition, Bax expression in liver tissue and aquaporin-2 (AQP-2) and nephrin expression in renal tissue were determined immunohistochemically. It was determined that oxidative damage caused by DOX decreased and improvement of liver and kidney function markers were observed in the groups that were treated with morin. In addition, pre-treatment of morin showed a regulatory effect on TNF-alpha, IL-1 beta and NF-kappa B levels. It prevented the increase in DOX-induced Bax expression and decrease in Bcl-2 level, AQP-2 and nephrin expression. Histopathological examination revealed that it prevented tissue damage in liver and kidney tissues.Öğe 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, ErdincThe 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.Öğe Protective effect of Smilax excelsa L. pretreatment via antioxidant, anti-inflammatory effects, and activation of Nrf-2/HO-1 pathway in testicular torsion model(Wiley, 2022) Cellat, Mustafa; Isler, Cafer Tayer; Uyar, Ahmet; Kuzu, Muslum; Aydin, Tuba; Etyemez, Muhammed; Turk, ErdincThe protective effects of the ethanol extract of Smilax excelsa L. (SE) leaves were investigated on testicular tissue of rats with a torsion model in this study. The chemical composition of the extract was detected by means of liquid chromatography with tandem mass spectrometry (LC-MS/MS). SE extract was given for 21 days before torsion was created in the treatment group. The sperm parameters of the torsion group were impaired, and there was an increase in MDA level as well as a decrease in GSH level and GPx activity compared to the control group. TNF-alpha and NF-kappa B levels in the torsion group increased as compared to those in the control group. The expression levels of Nrf-2 and HO-1 were lower in the torsion group than those in the control group. The SE pretreatment group has improved sperm, oxidative stress, and inflammatory markers when compared to the torsion group, and the Nrf-2/HO-1 pathway was activated. Practical applications Smilax excelsa L. is a plant with economic value used in traditional medicine in the treatment of stomachache, bloating, and breast cancer in Northwest Anatolia. It has an antioxidant effect due to the flavonoids and anthocyanins it contains. The protective effect against ischemia-reperfusion-induced tissue and reproductive damage in testicular tissue were demonstrated with the study. When the histological examinations of the tissues were evaluated, it was found that morphological structure of the tissues was retained in the treatment group. The findings indicate that SE prevents tissue damage in the torsion model by antioxidant and anti-inflammatory effects and activating Nrf-2/HO-1 pathway.Öğe Zingerone protects liver and kidney tissues by preventing oxidative stress, inflammation, and apoptosis in methotrexate-treated rats(Taylor & Francis Ltd, 2022) Turk, Erdinc; Guvenc, Mehmet; Cellat, Mustafa; Uyar, Ahmet; Kuzu, Muslum; Aggul, Ahmet Gokhan; Kirbas, AkinThe clinical use of drugs used in the treatment of diseases is limited due to the toxic side effects, and many studies have been conducted to benefit from herbal adjuvant therapies recently to eliminate these effects. In this study, the protective effect of zingerone against liver and kidney damage generated in rats through methotrexate (MTX). Histopathological investigations were performed to determine tissue damage caused by MTX and the healing effect of zingone and liver function markers such as serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and renal function markers such as urea, creatine, and aquaporin-1 (AQP-1) were measured. The effects of MTX and protective properties of zingerone on oxidative stress were investigated through the measurement of malondialdehyde and reduced glutathione (GSH) levels, catalase (CAT), and glutathione peroxidase (GPx) enzyme activities. The anti-inflammatory effect of zingerone was determined by measuring the cytokine levels causing inflammation such as nuclear factor-kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), and its effects on apoptosis were determined by immunohistochemical analysis of caspase-3 and B-cell lymphoma-2 (Bcl-2) expression levels. According to the results obtained within the scope of the study, it was determined that zingerone treatment prevented the increase in MTX-induced liver and kidney function markers, showed healing effects on antioxidant parameters degraded in both tissues, and decreased the inflammation parameters. It was determined that it also prevented apoptosis and possessed a protective effect on disrupted tissue architecture by decreasing the increased caspase-3 expression and increasing the decreased Bcl-2 level.
