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Öğe ANTI-INFLAMMATORY ACTIVITY OF TURKEY SOURCE PUMPKIN SEED OIL IN RAT EDEMA MODEL(Polskie Towarzystwo Farmaceutyczne, 2020) Arslanbas, Emre; Kara, Haki; Karayigit, Mehmet Onder; Dogan, Halef Okan; Yildiz, Seyma NurThis study aimed to determine the effects of Turkey-sourced pumpkin seed oil (PSO), administered orally to rats in different dosages, to research its anti-inflammatory effect in rat edema model, induced by carrageenan, based on different dosages, and to evaluate its effects comparatively with indomethacin. The study was conducted on 42 rats in total, divided into 7 groups (control, carr, PSO40, PSO100, PSO40+carr,PSO100+carr and indo+carr). In the study, doses of 40 and 100 mg/kg of PSO were found to significantly sup-press rat paw edema in time, and it was observed that this effect was more pronounced in the fourth hour. It was found that MDA and cytokine (TNF-alpha, IL-6, IL-1 beta) levels were inhibited, and GPX and SOD activities were enhanced in groups that received PSO and indo+carr groups. Histopathological examinations also support these findings. As a result of the study, the significant anti-inflammatory effect of Turkey-sourced PSO was attributed to the existence of unsaturated fatty acids and enriched phytochemical compounds.Öğe Canine Parvoviral Enteritis- The Role of MMP-9 and TIMP-1 in the Pathogenesis of Intestinal Inflammation(Univ Fed Rio Grande Do Sul, 2024) Karayigit, Mehmet Onder; Aydogan, Ahmet; Haligur, Mehmet; Basbug, Onur; Karatas, OzhanBackground: Canine parvoviral enteritis is a highly contagious infection in the intestines caused great morbidity and mortality in untreated dogs younger than 6 months. Matrix metalloproteinases consist of zinc- and calcium-dependent extracellular matrix-degrading endopeptidases that are tightly controlled by endogenous metalloproteinase tissue inhibitors. Canine parvoviral enteritis is common in Turkey. The aim of this study was to examine the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in natural canine parvoviral enteritis infection of 25 dogs diagnosed with parvoviral enteritis by clinical tests and histopathology. Materials, Methods & Results: The study material consists of dog's small intestine, which was brought to Cumhuriyet University Faculty of Veterinary Medicine pathology department for necropsy and diagnosed with parvoviral enteritis. This investigation was suported by the Comission of Scientific Research Projects of Cumhuriyet University (Project No: V-086). For the study, sections of 5 mu m were taken from small intestine blocks consisting of duodenum, jejunum and ileum, fixed in 10% buffered formalin solution and embedded in paraffin, and stained with hematoxylin-eosin and MMP-9 and TIMP-1 antibodies using immunohistochemical procedure. On histopathology, shedding and blunting of the villi epithelium, severe mononuclear inflammation in the lamina propria and locally enlarged crypts with lymphocytolysis in peyer's patches were noted in the ileum. Immunohistochemically, strong expression for MMP-9 and moderate expression for TIMP-1 were observed in the crypt epithelium and inflammatory cells in the small intestines of infected animals compared controls (P < 0.001). Discussion: In the present study, immunohistochemical expressions of MMP-9 and TIMP-1 in intestinal tissues were investigated in canine parvoviral enteritis, which is an important viral disease in veterinary medicine. Statistically strong expression for MMP-9 and moderate expression for TIMP-1 were observed in the crypt epithelium and inflammatory cells in the small intestines of infected animals. As a result, high levels of MMP-9 may be one of the factors that trigger the inflammatory process in the disease. It is thought that the increase in MMP-9 may be directly proportional to the severity of inflammation in the tissue. In addition, it is suggested that the level of its inhibitor, TIMP-1, may increase at similar rates in response to this increase in MMP-9 levels. As a result, severe increases MMP-9 and TIMP-1 may indicate the presence of inflammation of similar severity in that tissue. Immunohistochemical data obtained from the study showed that MMP-9 expression was found to increase in inflammatory and degenerative changes in parvoviral enteritis. This may have triggered extracellular matrix degradation, intestinal permeability, degenerative changes and inflammation. Abnormal increase in MMP-9 levels is thought to contribute significantly to the intestinal lesions in parvoviral enteritis. It was observed that TIMP-1 levels increased similarly in response to this increase but weaker expression of TIMP-1 as its inhibitor in canine parvoviral enteritis may determine the development of the disease. In this regard, matrix metalloproteinases appear to be potential therapeutic targets in canine parvoviral enteritis, and the use of their inhibitors can significantly reduce disease progression. However, current findings need to be confirmed by more detailed studies in the future.Öğe Estrogen and Progesterone Synthesis with Cellular Response in a C57BL/6 Mouse Model of Cuprizone-lnduced Demyelination(Univ Fed Rio Grande Do Sul, 2018) Karayigit, Mehmet Onder; Yarim, MuratBackground: Demyclination refers to the degradation or loss of myelin sheath. In demyelination model studies, it has been reported that demyclination is regressed by giving steroid hormones such as estrogen and progesterone. However, there are not many studies investigating the synthesis of these two hormones by the brain during demyelination and remyelination. Neurosteroids arc steroid hormones synthesized by the brain independently from peripheral tissues. In this study, it was aimed to have knowledge about the synthesis of these two hormones by the brain in experimentally formed demyelination process in brains of C57BL/6 mice and their role in the cellular response formed in the region. Materials, Methods & Results: In the study, 36 C57BL/6 mice were used: 12 mice were fed normal diet for 12 weeks as control group (Group I); 12 of them were fed 0.2% cuprizone diet for 8 weeks (Group II) and 12 mice were fed normal diet for 4 weeks after feeding cuprizone diet for 8 weeks (Group III). At the end of the experiment, mice were perfused with 4% paraformaldehyde and brain tissues were blocked in paraffin. 6 mu m-thick section was taken from each block. Sections were stained histologically with LFB staining and immunohistochemically with MBP staining in order to determine the demyelination in sections. All sections were also immunohistochemically stained with GFAP to detect astrocytes, with NG2 to detect young OPCs, with aromatase for estrogen synthesis and with 3 beta HSD antibodies for progesterone synthesis. At the end of the study, complete myelination was observed in group I, while severe demyelination was determined in group II as a result of blind evaluation of LFB and MBP staining by two pathologists. In group III, demyelination was found to be mild. In immunostaining with GFAP and NG2 antibodies, the number of GFAP and NG2 positive cells in Group II was found to be increased compared to the control group. The difference between these two groups was statistically significant (P < 0.01). In group III, the number of GFAP and NG2 positive cells were found to be increased compared to the control group; however, it was found to be lower than that in experimental group II (P < 0.01). In immunohistochemical staining with aromatase and 3 beta HSD antibody, there was no staining observed in the control groups. While an intense staining was observed in experimental group II, fewer glial staining was noticed in experimental group III when compared to the experimental group II. The difference between these two groups was found to be statistically significant (P < 0.01). Discussion: Aromatase is an enzyme that converts testosterone into estrogen. On the other hand, 3 beta HSD is an enzyme that converts pregnenolone to progesterone. Expression of aromatase from tissues refers to the synthesis of estrogen and expression of 3 beta HSD refers to progesterone synthesis. In previous demyelination studies carried out with cuprizone, it has been reported that demyelination is regressed by giving estrogen and progesterone during demyelination. In the presented study, we observed that enzyme levels that catalyze the synthesis of estrogen and progesterone increased during demyelination. In the study, it was determined that estrogen and progesterone levels were increased in the region by enzymes released from the glial cells of the brain as a response to damage formed during demyelination. Interestingly, during the period in which cuprizone was excluded from the diet, it was observed that remyelination began to be formed again and that enzyme levels synthesizing these hormones started to decrease. These results suggested that estrogen and progesterone may be synthesized in the brain after a damage and may contribute to remyelination by initiating a number of cell to cell signaling steps.Öğe IL-22 and Reg3? overexpression affects Experimental Autoimmune Encephalomyelitis Severity(Amer Assoc Immunologists, 2019) Eken, Ahmet; Yetkin, Mehmet Fatih; Okus, Fatma Zehra; Cakir, Mustafa; Karayigit, Mehmet Onder; Erdem, Serife; Haliloglu, Yesim[Abstract Not Available]Öğe Immunohistochemical expression of MMP-2 and MMP-9 in the brain tissue of sheep naturally infected with Listeria monocytogenes and relationship with cell death in the Listerial encephalitis(Univ Zulia, Facultad Ciencias Veterinarias, 2024) Karayigit, Mehmet Onder; Haligur, Mehmet; Ekici, MehmetListeria monocytogenes is an intracellular, food-borne bacterium. Silage is an important source of this pathogen causing listeriosis. Listeriosis is an important health problem for both animals and humans in the world. The disease comprises three clinical syndromes: meningoencephalitis, septicemia and metritis with abortion. Encephalitis is frequently observed and the factors that play a role in its pathogenesis are the subject of research. In this study, the immunohistochemical expression of MMP-2 and MMP-9 together with TUNEL staining was investigated in the pathogenesis of meningoencephalitis in sheep naturally infected with L. monocytogenes. The brains of 25 sheep with Listerial meningoencephalitis were used in this study. Brain material from 10 sheep provided from the slaughterhouse was also used as a control. Tissue sections were stained immunohistochemically with L. monocytogenes, MMP-2 and MMP-9 antibodies. Additionally, TUNEL staining was performed to determine apoptosis in the disease. As a result of the study, it was observed that TUNEL staining in neurons and glial cells, MMP-2 and MMP-9 expressions in vascular endothelial cells, inflammatory cells, microglia and especially neurons in the infected brain tissue were significantly increased compared to controls. These results suggested that MMP-2 and MMP-9 play an active role in the neurodegeneration and cell death that occur in Listerial encephalitis.Öğe Nitric Oxide Synthase Expression in Naturally Infected Sheep Brain with Listeria monocytogenes and Relationship with Cell Death(Univ Fed Rio Grande Do Sul, 2018) Karayigit, Mehmet OnderBackground: Nitric oxide is synthesized from L-arginine and catalyzed by a family of NOS. There are three different NOS isoforms: neuronal (nNOS), inducible (iNOS) and endothelial (eNOS). Nitric oxide is an important apoptosis regulator in mammalian system that can induce and prevent apoptosis depending on levels of NO production and environmental conditions of the cell. NOS expression and its relationship with apoptosis has not been well elucidated in listerial meningoencephalitis in sheep. The aim of this study was to investigate eNOS and iNOS expressions in the brain of sheep with natural listeriosis and to compare them with apoptosis which is shaped in the region. Materials, Methods & Results: In the study, formalin fixed and paraffin embedded brainstem tissue from 25 sheep naturally infected with LM were used from archives. Five Lan-thick section was taken from each block. Histopathologically, sections were stained with H&E. Five normal sheep brain tissues were used as control. At the end of the study, Histopathologically in brainstem tissue infected with LM, multifocal microabscesses in different sizes mixed with neutrophils and macrophages were detected and perivascular mononuclear cell infiltration and meningitis characterized by mononuclear cell infiltration were found. All sections were also immunohistochemically stained with I,M, eNOS and iNOS antibodies. In addition, TUNE!, method was used to determine apoptosis in brain tissues. As a result of immunostaining, listeria immunorcactivity was observed in microabscesses. The Listeria antigens were detected mainly in the cytoplasm of the neutrophils and macrophages and located extracellulary in microabscesses. Both eNOS and iNOS immunoreactivity were observed in very few neurons and glial cells in normal control sheep. Neurons and glial cells in brain tissues of infected animals stained with eNOS and iNOS. But, eNOS and iNOS expressions in listeriosis animals more higher than in control and the this difference was statistically significant (P < 0.05). At the same time, TUNEL immunopositivity was observed mainly in the nuclei of neuron and glial cells and this findings was found to be significantly increased compared to the control group (P < 0.05). Discussion: The pathogenesis of listerial meningoencephalitis depends on many factors and is still a subject of research. NO is a pluripotent regulator of diverse cellular functions. NOS can trigger cellular damage. However, there are studies suggesting that it can prevent oxidative stress. eNOS and iNOS expressions may vary depending on disease and animal species. Increased levels of NO have been reported to induce apoptosis in many diseases. However, there are studies indicating that NO is able to prevent apoptosis according to the isoform in which it is synthesized. eNOS and iNOS have not been reported together expressions and with their relationship apoptosis in sheep brain with listerial meningoencephalitis. This is the first study of eNOS and iNOS expression and and its relation to cell death in sheep brain infected with LM. Our findings are consistent with previous studies suggesting that NO expression is effective on the pathogenesis of some disease in the central nervous system. However, there are studies that do not match the findings of the present study. This suggests that the role of NO synthesis in the pathogenesis of diseases may vary according to the amount of expression, type of disease and tissue, or animal species. In the present study showed that the expression of both eNOS and iNOS with increased TUNEL positive cells was statistically significant in the listeriosis compared the control brain tissue. These results suggests that eNOS and iNOS can be expressed by diverse brain cells in the pathogenesis of listeriosis in sheep. In addition this, synthesis of NO can induce the apoptosis in sheep brain with listerial meningoencephalitis.Öğe Schisandrin B and Alantolactone ameliorates experimental autoimmune encephalomyelitis in mice(Amer Assoc Immunologists, 2020) Eken, Ahmet; Cakir, Mustafa; Karayigit, Mehmet Onder; Altuntas, Hamiyet Donmez[Abstract Not Available]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.
