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Öğe Assessment of the protective effects of pomegranate peel extract and N-acetyl cysteine alone or in combination with Ornipural® against Cadmium-induced bone toxicity in rat(2024) Hatipoglu, Durmus; Demircioglu, İsmail; Filikci, Kursat; Korkmaz, Yasemin; Gungor, Huseyin; Demircioglu, Muhammed; Dik, BurakAim: The present study was conducted to determine the effects of pomegranate peel extract (PPE) and N-acetyl Cysteine (NAC) alone or in their treatment combinations with commercial preparation Ornipural® (ORN) on bone metabolism against experimentally cadmium (Cd)-induced toxicity in rats. Materials and Methods: Totally 36 animals were used in the study including 6 Wistar Albino rats in each group. The animals were assigned to control, Cd, Cd+PPE, Cd+NAC, Cd+PPE+ORN and Cd+NAC+ORN groups. The animals in the groups were euthanized after their blood samples were taken at the end of the 8th week. The bones were subjected to maceration for morphometric and histopathological examinations after euthanasia. Results: The statistically significant differences were determined between the treatment groups and Cd group in terms of histopathological changes (osteoporotic alterations and changes in red bone marrow) and biomarkers (Ca, P and Mg) (P<0.05). Conclusion: Although PPE, NAC and treatment combinations with ORN applied against experimentally induced cadmium toxicity were determined to have positive effects on bone metabolism, it has been thought that carrying out trials by increasing treatment duration and dose would be beneficial to determine definite efficacy of the applied treatment protocols.Öğe Cherry stem phenolic compounds: Optimization of extraction conditions and in vitro evaluations of antioxidant, antimicrobial, antidiabetic, anti-inflammatory, and cytotoxic activities(Wiley, 2020) Demir, Tugba; Akpinar, Ozlem; Kara, Haki; Gungor, HuseyinThe present study reported the optimization of extraction of phenolic and flavonoid compounds from the cherry stem and biological activities of the extract. The extraction parameters were optimized employing a response surface methodology, and they were determined as 79 degrees C, 35% (vol/vol) of ethanol percentage and 119 min. It was found that the extract obtained at the optimum conditions contained high amounts of sinapic acid and quercetin followed by caffeic and ferulic acid. It had a high antioxidant capacity and showed antimicrobial activities againstEscherichia coli,Enterococcus fecalis,Staphylococcus aureus,Aspergillus flavus,andAspergillus niger. The extract inhibited alpha-amylase, alpha-glucosidase, lipoxygenase, and xanthine oxidase enzymes which indicated that the extract had antidiabetic and anti-inflammatory effects. It also showed cytotoxic activities on the breast and bone cancer cells. The results showed that cherry stems might be potentially useful in food or nonfood applications and an important natural source for bioactive compounds. Practical applications The cherry stem extract showed the high antioxidant, antimicrobial, antidiabetic, and anti-inflammatory activities. It displayed cytotoxicity against MCF-7 and MG-63 cells. It can replace the chemical compounds in food and nonfood formulations to control the oxidative change and undesirable microbial activity and can reduce the blood glucose levels, inflammation and the risk of cancer, and it can meet the increasing consumer demand to the natural products.Öğe Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of d-galactose-induced aging mice(TAYLOR & FRANCIS LTD, 2016) Turgut, Nergiz Hacer; Mert, Derya Guliz; Kara, Haki; Egilmez, Hatice Reyhan; Arslanbas, Emre; Tepe, Bektas; Gungor, Huseyin; Yilmaz, Nese; Tuncel, Necati BarisContext: Morus nigra L. (Moraceae) has various uses in traditional medicine. However, the effect of M. nigra on cognitive impairment has not been investigated yet. Objective: The objective of this study is to determine the phenolic acid content and DNA damage protection potential of M. nigra leaf extract and to investigate the extract effect on cognitive impairment and oxidative stress in aging mice. Materials and methods: Phenolic acid content was determined by quantitative chromatographic analysis. DNA damage protection potential was evaluated on pBR322 plasmid DNA. Thirty-two Balb-C mice were randomly divided into four groups (control, d-galactose, d-galactose + M. nigra 50, and d-galactose + M. nigra 100). Mice were administered d-galactose (100 mg/kg, subcutaneous) and M. nigra (50 or 100 mg/kg, orally) daily for 8 weeks. Behavioral responses were evaluated with Morris water maze. Activities of antioxidant enzymes and levels of malondialdehyde (MDA) were assayed in serum, brain, and liver. Results: In extract, vanillic (632.093 mu g/g) and chlorogenic acids (555.0 mu g/g) were determined. The extract between 0.02 and 0.05 mg/mL effectively protected all DNA bands against the hazardous effect of UV and H2O2. Morus nigra significantly improved learning dysfunctions (p< 0.01), increased memory retention (p < 0.01), reduced MDA levels (p < 0.05), and elevated SOD, GPx, and CAT activities (p < 0.05) compared with the d-galactose group. Discussion and conclusion: These results show that M. nigra has the potential in improving cognitive deficits in mice and that M. nigra may be useful to suppress aging, partially due to its scavenging activity of free radicals and high antioxidant capacity.Öğe Effects of apixaban, rivaroxaban, dabigatran and enoxaparin on histopathology and laboratory parameters in Achilles tendon injury: An in vivo study(Wolters Kluwer Medknow Publications, 2021) Avci, Sema; Gungor, Huseyin; Kumru, Alper Serhat; Sahin, Mahmut; Gezer, Arzu; Gok, Uzeyir; Kara, HakiObjectives: To compare the effects of apixaban, rivaroxaban, dabigatran and enoxaparin on histopathology and blood parameters in rats with Achilles tendon injury. Materials and Methods: Thirty adult, male Wistar albino rats weighting 220-240 g were randomly divided into five (one control and four treatment) groups and placed in a controlled environment. The Achilles tendon was incised and re-sutured in each rat, after which each group was provided the following treatment for 28 days: a) 2 ml saline to the control group, b) apixaban in 1 ml of saline (10 mg/kg/day) +1 ml of saline, c) rivaroxaban in 1 ml of saline (2 mg/kg/day) +1 ml saline, d) dabigatran in 1 ml of saline (30 mg/kg/day) +1 ml of saline, e) enoxaparin (80 mu g/kg/day) + 2 ml of saline. Results: Hemogram, biochemical and coagulation parameters differed significantly between the control and treatment groups (P < 0.05). Compared with the control group, in the apixaban group, type I and type III collagen immunoreactivity were severe and moderate, respectively. In the rivaroxaban and dabigatran groups, both type I and type III collagen immunoreactivity were medium and severe, respectively. In the enoxaparin group, type I and type III collagen immunoreactivity were mild and severe, respectively. Conclusion: The higher concentration of type I collagen in the apixaban and dabigatran indicates faster tendon healing in these groups, and the higher concentration of the type III collagen in the enoxaparin group indicates slower healing in this group.Öğe Effects of selenium, zinc, insulin and metallothionein on cadmium-induced oxidative stress and metallothionein gene expression levels in diabetic rats(De Gruyter, 2020) Gungor, Huseyin; Kara, HakiThe aim of this study was to investigate the effects of selenium, zinc, insulin, and metallothionein on oxidative damage and metallothionein (MT) gene expression levels in streptozotocin (STZ)-induced type 1 diabetic rats exposed to Cd. Rats were categorized under eight groups (control, STZ, Cd, STZ + Cd, Group 5, Group 6, Group 7, and STZ + Cd + MT [n:8/group]) were used. After diabetes was induced by STZ (55 mg/kg, i.p.), Cd was administered (1 mg/kg CdCl, orally) for 4 weeks. In cadmium-treated groups selenium (Na2SeO3 1.5 mg/kg, i.p.), zinc (ZnSO4 10 mg/kg via oral gavage), insulin (insulin glargine, 2U/day, s.c.), and MT (1mg/kg, every other 10 days, s.c.) were administered. MT gene expression levels, MDA levels, GPx, SOD, and CAT activity levels were determined in liver and kidney tissues. MT gene expression and MDA levels increased (p < 0.05) while GPx and SOD activity levels decreased (p < 0.05) in STZ, Cd, and STZ + Cd groups. In Group 5, Group 6, Group 7, and Group 8 groups MT gene expression and MDA levels were decreased while GPx and SOD activity levels were increased (p < 0.05). CAT activity significantly increased (p < 0.05) in STZ + Cd group while there were no significance in other groups (p > 0.05). Compared to the control, Group 5, Group 6, Group 7, and Group 8 groups provided no difference for alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine levels (p > 0.05). Our results suggest that Se, insulin, Zn and MT may have protective effects against hepatotoxicity and nephrotoxicity caused by Cd exposure in diabetic rats by reducing oxidative stress and MT gene expression levels. © 2020 2020 Walter de Gruyter GmbH, Berlin/Boston.Öğe Enoxaparin pretreatment alleviates pentylenetetrazol-induced epileptic seizures in Wistar rats(Univ Zulia, Facultad Ciencias Veterinarias, 2024) Gungor, Huseyin; Turgut, Nergiz HacerEpilepsy, is a prevalent neurological disorder characterized by recurring seizures. A low molecular weight heparin enoxaparin has multifaceted properties. In addition to its anticoagulant activity, enoxaparin has demonstrated anti-inflammatory, antioxidant and anti-apoptotic effects. Accordingly, the purpose of this study was to evaluate the protective effect of enoxaparin against seizures, oxidative stress, proinflammatory cytokines, apoptosis, brain-derived neurotropic factor (BDNF) concentrations and cognitive impairment in pentylenetetrazole (PTZ) induced kindling in Wistar rats. Twenty-four rats divided into 4 groups (Control, PTZ, ENX250+PTZ, ENX500+PTZ) were used. Enoxaparin (250 and 500 IUkg(-1) , intraperitoneal-ip-) or vehicle (saline) were given to rats for 5 days. On the fifth day, 30 min after drug administration, PTZ (45 mgkg(-1) , ip) was given to cause seizures. Behavioral seizure parameters were evaluated by video recording. A behavioral test, passive avoidance test was performed. PTZ administration decreased total antioxidant status (TAS) while increased total oxidant status (TOS) both in hippocampus and cortex. Furthermore, PTZ induced elevated levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), BDNF, caspase-3, and caspase-9. Pretreatment with enoxaparin decreased the levels of these parameters and TOS, while increased TAS. Enoxaparin pretreatment significantly decreased the epileptic seizure scores according to the Racine scale, increased first myoclonic jerk (FMJ) time and the test trial time in passive avoidance test. These results indicate that enoxaparin (250 and 500 IUkg(-1)) at both doses has promising protective effect against PTZ induced epilepsy by improving memory impairment, inflammation, oxidative stress and apoptosis. This positive effect was more prominent at 500 IUkg(-1) dose of enoxaparin.Öğe The influence of quercetin on recognition memory and brain oxidative damage in a ketamine model of schizophrenia(TAYLOR & FRANCIS LTD, 2019) Mert, Derya Guliz; Turgut, Nergiz Hacer; Arslanbas, Emre; Gungor, Huseyin; Kara, HakiOBJECTIVE: The aims of this study were to investigate the protective effect of quercetin on changes in recognition memory as assessed by the novel object recognition (NOR) test, as well as on changes in the oxidative stress levels in the hippocampus and prefrontal cortex, produced in a model of memory impairment in schizophrenia induced by administration of a subanesthetic dose of ketamine. METHODS: A total of 40 Balb-C mice were randomly divided into five groups (Corn oil + Saline, Quercetin 50 + Saline, Corn oil + Ketamine, Quercetin 25 + Ketamine, Quercetin 50 + Ketamine). Corn oil and Quercetin (25 or 50 mg/kg/day) was given by orogastric gavage once daily for 21 days. Corn oil was chosen as the vehicle and administered at the same volume as quercetin. Ketamine was injected at a dose of 25 mg/kg intraperitoneally (i.p.) for a period of 7 days starting from the 15th day. Behavioural responses were evaluated with the NOR test. The activity levels of antioxidant enzymes and levels of malondialdehyde (MDA) were assayed in the prefrontal cortex and hippocampus. RESULTS: The time of exploration of the novel object was longer than T-F (time to explore the familiar object) in the Corn oil + Saline and Quercetin 50 + Saline groups in NOR Test-1 (p < .05). The discrimination ratios of the Quercetin 50 + Ketamine and Corn oil + Ketamine groups were significantly lower than that of the Quercetin 50 + Saline group (p < .05). The discrimination ratios of the Quercetin 50 + Ketamine and Corn oil + Saline groups were significantly lower than that of the Quercetin 50 + Saline group (p < .05). The time of exploration of the novel object was longer than T-F in the Corn oil + Saline and Quercetin 50 + Ketamine groups in NOR Test-2 (p < .05). The discrimination ratios of the Corn oil + Ketamine and Quercetin 25 + Ketamine groups were significantly lower than those of the Quercetin 50 + Ketamine group (p < .05). Quercetin at 50 mg/kg reduced the MDA levels and elevated the SOD and GPx activity compared to the Corn oil + Ketamine group. CONCLUSION: These results show that quercetin has the potential to improve cognitive deficits in mice and that quercetin may be useful for treating the symptoms of schizophrenia, partially due to its ability to scavenge free radicals and its high antioxidant capacity.Öğe Pharmacokinetics of meloxicam following intravenous administration at different doses in sheep(Wiley, 2024) Gungor, Huseyin; Corum, Orhan; Corum, Duygu Durna; Kumru, Alper Serhat; Yilmaz, Gokhan; Coskun, Devran; Coskun, AlparslanThe aim of this study is to determine the pharmacokinetic change after intravenous administration of meloxicam at doses of 0.5, 1 and 2 mg/kg to sheep. The study was carried out on six Akkaraman sheep. Meloxicam was administered intravenously to each sheep at 0.5, 1, and 2 mg/kg doses in a longitudinal pharmacokinetic design with a 15-day washout period. Plasma concentrations of meloxicam were determined using the high performance liquid chromatography-ultraviolet, and pharmacokinetic parameters were evaluated by non-compartmental analysis. Meloxicam was detected up to 48 h in the 0.5 mg/kg dose and up to 96 h in the 1 and 2 mg/kg doses. As the dose increased from 0.5 to 2 mg/kg, terminal elimination half-life, and dose normalized area under the concentration versus time curve increased and total clearance decreased. Compared to the 1 mg/kg dose, it was determined that V(dss )decreased and C-0.083h increased in the 2 mg/kg dose. Meloxicam provided the therapeutic concentration of >0.39 mu g/mL reported in other species for 12, 48 and 96 h at 0.5, 1 and 2 mg/kg doses, respectively. These results show that meloxicam exhibits non-linear pharmacokinetics and will achieve unpredictable plasma concentrations when administered IV for a rapid effect at dose of >= 1 mg/kg in sheep.Öğe The Protective Effect of Naringin against Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats(HINDAWI LTD, 2016) Turgut, Nergiz H.; Kara, Haki; Elagoz, Sahende; Deveci, Koksal; Gungor, Huseyin; Arslanbas, EmreThe aim of the current study was to investigate the protective effect of naringin on bleomycin-induced pulmonary fibrosis in rats. Twenty-four Wistar rats randomly divided into four groups (control, bleomycin alone, bleomycin + naringin 40, and bleomycin + naringin 80) were used. Rats were administered a single dose of bleomycin (5mg/kg; via the tracheal cannula) alone or followed by either naringin 40 mg/kg (orally) or naringin 80mg/kg (orally) or water (1mL, orally) for 14 days. Rats and lung tissue were weighed to determine the lung index. TNF-alpha and IL-1 beta levels, hydroxyproline content, and malondialdehyde (MDA) levels were assayed. Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were determined. Tissue sections were stained with hematoxylin-eosin, Masson's trichrome, and 0.1% toluidine blue. TNF-alpha, IL-1 beta, and MDA levels and hydroxyproline content significantly increased (p < 0.01) and GPx and SOD activities significantly decreased in bleomycin group (p < 0.01). Naringin at a dose of 80mg/kg body weight significantly decreased TNF-alpha and IL-1 beta activity, hydroxyproline content, and MDA level (p < 0.01) and increased GPx and SOD activities (p < 0.05). Histological evidence supported the results. These results show that naringin has the potential of reducing the toxic effects of bleomycin and may provide supportive therapy for conventional treatment methods for idiopathic pulmonary fibrosis.Öğe Protective effect of PDE4B subtype-specific inhibition in an App knock-in mouse model for Alzheimer's disease(Springernature, 2024) Armstrong, Paul; Gungor, Huseyin; Anongjanya, Pariya; Tweedy, Clare; Parkin, Edward; Johnston, Jamie; Carr, Ian M.Meta-analysis of genome-wide association study data has implicated PDE4B in the pathogenesis of Alzheimer's disease (AD), the leading cause of senile dementia. PDE4B encodes one of four subtypes of cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase-4 (PDE4A-D). To interrogate the involvement of PDE4B in the manifestation of AD-related phenotypes, the effects of a hypomorphic mutation (Pde4b(Y358C)) that decreases PDE4B's cAMP hydrolytic activity were evaluated in the App(NL-G-F) knock-in mouse model of AD using the Barnes maze test of spatial memory, 14C-2-deoxyglucose autoradiography, thioflavin-S staining of beta-amyloid (A beta) plaques, and inflammatory marker assay and transcriptomic analysis (RNA sequencing) of cerebral cortical tissue. At 12 months of age, App(NL-G-F) mice exhibited spatial memory and brain metabolism deficits, which were prevented by the hypomorphic PDE4B in App(NL-G-F)/Pde4b(Y358C) mice, without a decrease in A beta plaque burden. RNA sequencing revealed that, among the 531 transcripts differentially expressed in App(NL-G-F) versus wild-type mice, only 13 transcripts from four genes - Ide, Btaf1, Padi2, and C1qb - were differentially expressed in AppNL-G-(F)/Pde4bY358C versus App(NL-G-F) mice, identifying their potential involvement in the protective effect of hypomorphic PDE4B. Our data demonstrate that spatial memory and cerebral glucose metabolism deficits exhibited by 12-month-old AppNL-G-F mice are prevented by targeted inhibition of PDE4B. To our knowledge, this is the first demonstration of a protective effect of PDE4B subtype-specific inhibition in a preclinical model of AD. It thus identifies PDE4B as a key regulator of disease manifestation in the App(NL-G-F) model and a promising therapeutic target for AD.Öğe Reply to Letter to the Editor: Can ARNI Prevent Doxorubicin-Induced Cardiotoxicity?(Aves, 2022) Dindas, Ferhat; Gungor, Huseyin; Ekici, Mehmet; Akokay, Pinar; Erhan, Fusun; Dogdus, Mustafa; Yilmaz, Mehmet Birhan[Abstract Not Available]Öğe The Effect of Greater Celandine Active Ingredient Chelidonine on Isolated Rat Bladder and Trachea Smooth Muscles and Primary Lung and Kidney Cell Lines(Kafkas Univ, Veteriner Fakultesi Dergisi, 2020) Arslanbas, Emre; Kara, Haki; Turgut, Nergiz Hacer; Gungor, Huseyin; Dogan, Halef Okan; Atasoy, Mustafa Ozan; Kumru, Alper SerhatThis study aims to explore the pharmacodynamics of chelidonine, the active ingredient in greater celandine (Chelidonium majus L.), on in vitro rat bladder and trachea tissue, and evaluate its cell protective effects on primary lung and kidney cell lines. The study was carried out via repeated applications of acetylcholine, atropine, verapamil and oxybutynin, alongside Ca++ in a calcium-free environment, on urinary bladder tissue, and repeated applications of acetylcholine, atropine, carbachol and mecamylamine on trachea tissue. At the same time, cell viability and catalase and superoxide dismutase activity was measured on primary cell lines obtained from lung and kidney tissue samples. The study has shown that chelidonine has a relaxant effect on bladder and trachea tissues, and it may be mentioned that this effect is produced via muscarinic receptors. In addition, chelidonin caused a statistically insignificant increase in cell viability in primary lung and kidney cell lines at increasing doses (1 and 4 mu g/mL), but this increase remained at the control group level. In contrast, chelidonin caused a significant decrease in cell viability at the same cell lines at doses of 8 and 16 mu g/mL. In conclusion, it is suggested that greater celandine, which is used in folk medicine, and its active ingredient chelidonine might have beneficial effects on asthma, urinary incontinence and other urinary tract and respiratory diseases among others.Öğe Zingerone ameliorates oxidative stress and inflammation in bleomycin-induced pulmonary fibrosis: modulation of the expression of TGF-?1 and iNOS(Springer, 2020) Gungor, Huseyin; Ekici, Mehmet; Karayigit, Mehmet Onder; Turgut, Nergiz Hacer; Kara, Haki; Arslanbas, EmreIdiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with limited treatment options. Zingerone found in ginger (Zingiber officinale L.) has many pharmacological effects, especially antiinflammatory and antioxidant activity. However, the effect of zingerone on pulmonary fibrosis (PF) is not fully known. The aim of this study was to investigate the effect of zingerone on bleomycin (BLM)-induced PF and its underlying mechanisms. Wistar-albino rats were given single dose of BLM (5 mg/kg, intratracheal) or vehicle (saline). In treatment groups, zingerone (50 and 100 mg/kg, p.o.) was administered orally for 14 days after BLM administration. Rats and lung tissue were weighed to determine lung index. Antioxidant, antiinflammatory effects, and hydroxyproline content of zingerone were determined by ELISA method. Pulmonary inflammation, collagen deposition, and fibrosis score were determined with Hematoxylin-Eosin (HxE) and Masson's trichrome staining. Transforming growth factor-beta 1 (TGF-beta 1) and inducible nitric oxide synthase (iNOS) expressions were detected immunohistochemically. BLM administration increased lipid peroxidation (MDA) and decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. In addition, BLM caused increased levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in bronchoalveolar lavage fluid (BALF) and accumulation of collagen bundles. Zingerone administration decreased collagen accumulation, TNF-alpha and IL-1 beta levels, MDA level, TGF-beta 1, and iNOS expression and increased SOD and GPx activity. Histopathological findings supported the results. These results show that zingerone (50 and 100 mg/kg) at both doses significantly contributes to healing of PF by improving inflammation, oxidative stress, and histopathological alterations and by affecting TGF-beta 1 and iNOS signaling pathways.
