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Öğe Doxycycline and meloxicam can treat neuroinflammation by increasing activity of antioxidant enzymes in rat brain(Univ Karachi, 2019) Dik, Burak; Coskun, Devran; Bahcivan, Emre; Er, AyseThe aim of this study is to determine the effects of alone or combined usage of doxycycline and meloxicam on brain superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and matrix metalloproteinase (MMP)-9 levels of lipopolysaccharide (LPS)-induced brain inflammation. Totally 78 rats were divided into 5 groups; Healthy control (n=6), LPS (n=18, 0.05 mu g/mu L/rat, intracranially), LPS+D (n=18, LPS 0.05 mu g/mu L/rat, intracranially and doxycycline 40 mg/kg, intraperitoneally), LPS+M (n=18, LPS 0.05 mu g/mu L/rat, intracranially and meloxicam 2 mg/kg, intraperitoneally), LPS+Combination (n=18, LPS 0.05 mu g/mu L/rat, intracranially and simultaneously both drug combination) groups. Animals were euthanized at 1, 3 and 6 hours following injections and the brains were removed. Brain SOD, CAT, MDA and MMP-9 levels were determined by ELISA reader. Parameters of LPS groups generally different from Healthy control group. When compared to LPS group, increased SOD level of LPS+D at 3 hours and CAT levels of LPS+M and LPS+D groups were determined (P<0.05) at 3 and 6 hours, respectively. In addition, all treatments statistically significantly (P<0.05) decreased MMP-9 levels at 6 hours. In conclusion, doxycycline and meloxicam may show antioxidant effect via increasing antioxidant enzyme production in the brain; however combined usage of drugs may show more beneficial effect for neuroinflammation.Öğe Effect of doxycycline and meloxicam on cytokines, brain-derived neurotrophic factor, matrix metalloproteinase-3, tissue inhibitor of metalloproteinase-3 and cyclooxygenase-2 in brain(Mashhad Univ Med Sciences, 2020) Er, Ayse; Coskun, Devran; Bahcivan, Emre; Dik, BurakObjective(s): Prevention of inflammation in early stages will be useful in maintaining vitality of the organism. The objective of this study was to evaluate the effects of doxycycline (DOX) or meloxicam (MLX) monotherapy and combination therapy on the levels of inflammatory mediators in the brain tissues of rats with Escherichia coli lipopolysaccharide (LPS)-induced brain inflammation. Materials and Methods: Seventy-eight rats were divided into the following groups: control (n=6), LPS (0.5 mu g/10 mu l intracranial) (n=18), LPS (0.5 mu g/10 mu l intracranial)+DOX (40 mg/kg intraperitoneal) (n=18), LPS (0.5 mu g/10 mu l intracranial)+MLX (2 mg/kg intraperitoneal) (n=18) and LPS (0.5 mu g/10 mu l intracranial)+DOX (40 mg/kg intraperitoneal)+MLX (2 mg/kg intraperitoneal) (n=18) groups. Brain tissues were harvested from all rats in the control group and from six rats each in the four experimental groups at 1, 3 and 6 hr under anaesthesia. The levels of tumor necrosis factor alpha (TNF alpha), interleukin 4 (IL-4), IL-6, IL-10, IL-17, brain-derived neurotrophic factor (BDNF), matrix metalloproteinase 3 (MMP-3), tissue inhibitor of metalloproteinase 3 (TIMP-3) and cyclooxygenase 2 (COX-2) in the brain tissues were measured using ELISA kits with ELISA device. Results: LPS administration increased proinflammatory cytokines (TNF, IL-6, IL-17), and MMP-3 levels and decreased anti-inflammatory cytokines (IL-10, IL-4), and BDNF levels. The lowest TNF alpha levels were detected in the LPS+MLX group (P<0.05). All the drug treatment groups showed decreased IL-17 and COX-2 levels compared to the LPS groups. Conclusion: DOX or MLX monotherapy exerts neuroprotective effects against brain inflammation by decreasing proinflammatory cytokine levels and by increasing anti-inflammatory cytokines levels.Öğe Potential antidiabetic activity of benzimidazole derivative albendazole and lansoprazole drugs in different doses in experimental type 2 diabetic rats(Tubitak Scientific & Technological Research Council Turkey, 2021) Dik, Burak; Coskun, Devran; Bahcivan, Emre; Uney, KamilAim: The aim of this study is to determine the effects of different concentrations of albendazole and lansoprazole, which were benzimidazole derivatives, on endocrinologic and biochemical parameters in experimental type 2 diabetic (T2D) rats. Materials and methods: In this study, 46 male Wistar Albino rats were used. Animals were divided as healthy control (0.1 mL/rat/day saline, s.c, n = 6), diabetes control (0.1 mL/rat/day saline, s.c, n = 8), diabetes+low-dose albendazole (5 mg/kg, oral, n = 8), diabetes+high-dose albendazole (10 mg/kg, oral n = 8), diabetes+low-dose lansoprazole (15 mg/kg, subcutaneous, n = 8), and diabetes+high-dose lansoprazole (30 mg/kg, subcutaneous, n = 8). All groups were treated for 8 weeks. The blood samples were analyzed by autoanalyzer and ELISA kits for biochemical and endocrinological parameters, respectively. Results: Glucose, HbA1c, triglyceride, low density cholesterol (LDL), leptin, and Homeostatic Model Assessment for insulin resistance (HOMA-IR) levels increased and insulin and HOMA-beta levels decreased in the diabetic rats compared to the healthy control group. The glucose, HbA1c, and triglyceride levels were partially decreased; however, insulin and HOMA-beta levels were increased by low-dose albendazole therapy. The high dose of lansoprazole treatment increased insulin level. Conclusion: The lansoprazole and albendazole treatments can be a potential drug or combined with antidiabetic drugs in T2D treatment by Adenosine 5'-monophosphate activated protein kinase (AMPK), peroxisome proliferator-activated receptor (PPAR), incretin-like effect and other antidiabetic mechanisms. It may be beneficial to create an effective treatment strategy by developing more specific substances with benzimidazole scaffold.Öğe The impact of ambroxol on the anti-inflammatory effect of azithromycin in lung tissue(Univ Zagreb Vet Faculty, 2021) Er, Ayse; Dik, Burak; Coskun, Devran; Faki, Hatice Eser; Bahcivan, EmreThe aim of this study was to compare the effects of two different doses of ambroxol (AMB) co-administered with azithromycin (AZIT) on the concentrations of bronchoalveolar lavage fluid (BALF) cytokines and serum biochemical parameters in an lipopolysaccharide (LPS)-induced acute lung injury mouse model. A total of 78 male Swiss albino mice were used for this investigation. After six mice had been separated as the control group (0 hours), the remaining animals were divided into the following three equal groups: LPS, LPS+AZIT+AMB30 and LPS+AZIT+AMB70. LPS, AZIT and AMB were administered intraperitoneally. BALF and serum samples were collected before (0 hour) and after applications at 4, 8, 16 and 24 hours under general anaesthesia, and then all mice were euthanised by cervical dislocation. Concentrations of tumor necrosis factor (TNF)alpha, interleukin (IL)-6 and IL-10 in BALF and aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea and creatinine concentrations in serum were determined. Elevated TNF alpha and IL-6 concentrations in the LPS group were prevented at 8 and 16 hours in LPS+AZIT+AMB30 group. In addition, both treatment groups inhibited elevated IL-6 concentrations in the LPS group at 16 hours. LPS+AZIT+AMB30 and LPS+AZIT+AMB70 increased IL-10 concentrations at 16 and 4 hours, respectively. LPS caused significant elevations in urea concentrations at all sampling times and statistical fluctuations in other parameters at different sampling times. The increased ALP concentration in LPS group decreased in the treatment groups at 8 hours. In conclusion, the combination of low-dose AMB and AZIT may achieve beneficial effects in pulmonary infections by influencing the cytokine network.
