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    Anti-inflammatory properties of Liposome-encapsulated clodronate or Anti-Ly6G can be modulated by peripheral or central inflammatory markers in carrageenan-induced inflammation model
    (Springer Basel Ag, 2019) Mert, Tufan; Şahin, Mehmet; Şahin, Emel; Yaman, Selma
    Overproduction of inflammatory markers by immune cells, such as macrophages and neutrophils, is one of the main reasons for many inflammatory conditions and inhibiting or suppressing of their production by cell depletion may provide new therapeutic targets or approaches to prevent a variety of inflammatory conditions. In this study, we examined the possible effects of anti-Ly6G-mediated systemic neutrophil depletion and liposome-encapsulated clodronate (LEC)-mediated systemic macrophage depletion on the inflammatory signs (thermal hyperalgesia, mechanical allodynia, oedema and fever) and measured the levels of various inflammation markers (tumour necrosis factor- (TNF-), interleukins (IL)-1, IL-4, IL-10, macrophage inflammatory protein-1 alpha (MIP-1/CCL3) and myeloperoxidase (MPO) in paw and spinal cord tissues in carrageenan (CG)-induced hindpaw inflammation model in rats. CG injection into the paw caused inflammation characterized by redness, swelling, heat and pain hypersensitivities. Anti-Ly6G or LEC significantly ameliorated the pain behaviours, and decreased the oedema and fever. Efficacies of anti-Ly6G or LEC on inflammatory responses changed depend on the degree of inhibition in inflammatory markers of inflamed paw or spinal cord. Anti-inflammatory properties of anti-Ly6G or LEC suggest that macrophages and/or neutrophil-mediated inflammatory cascade in inflamed site and spinal cord which can play key roles in inflammatory pain responses. These systemic or peripheral inflammatory mediators may be therapeutic targets in the treatment of many inflammatory conditions and related various diseases.
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    Antiinflammatory properties of antiLy6G antibody disappear during magnetic field exposure in rats with carrageenan induced acute paw inflammation
    (Springer, 2020) Mert, Tufan; Metin, Tuba Özcan; Şahin, Mehmet; Yaman, Selma
    Antiinflammatory properties of pulsed magnetic field (PMF) treatments or administration of antiLy6G antibody have been previously reported. In this study, we hypothesized that, the combination of PMF treatments and antiLy6G administration may synergistically potentiate their antiinflammatory actions. The effects of the combination of PMF treatments and antiLy6G administration were investigated by examining the inflammatory signs, histopathological properties of the inflamed site, and measuring the macrophage inflammatory protein-1 alpha (MIP-1 alpha/CCL3) and myeloperoxidase (MPO) levels of inflamed paw tissues in rats with carrageenan-induced acute paw inflammation. In this present study, PMF treatments alone or administration of antiLy6G alone ameliorated the acute inflammation. However, their combination exacerbated the inflammatory signs, hyperalgesia, allodynia, edema and fever, and aggravated the inflammatory conditions by excessive infiltration of inflammatory cells to the inflamed site. These opposing effects of the combined treatments may correlate with enhanced levels of MIP-1 alpha and MPO in inflamed paws. Present results indicated that the combination of the PMF treatments and antiLy6G administration may not provide additional benefits and may actually cause an aggravation of the acute inflammatory process. Findings may also suggest that during neutrophil or immune cell-targeted treatments for inflammatory states, magnetic field exposure may cause unexpected negative consequences.
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    Effects of immune cell-targeted treatments result from the suppression of neuronal oxidative stress and inflammation in experimental diabetic rats
    (Springer, 2020) Mert, Tufan; Şahin, Emel; Yaman, Selma; Şahin, Mehmet
    In this study, we hypothesized that reduction of immune cell activation as well as their oxidant or inflammatory mediators with minocycline (MCN), liposome-encapsulated clodronate (LEC), or anti-Ly6G treatments can be neuroprotective approaches in diabetic neuropathy. MCN (40 mg/kg) for reduction of microglial activation, LEC (25 mg/kg) for of macrophage inhibition, or anti-Ly6G (150 mu g/kg) for neutrophil suppression injected to streptozotocin (STZ)-induced diabetic rats twice, 3 days, and 1 week (half dose) after STZ. Animal mass and blood glucose levels were measured; thermal and mechanical sensitivities were tested for in pain sensations. The levels of chemokine C-X-C motif ligand 1 (CXCL1), CXCL8, and C-C motif ligand 2 (CCL2), CCL3, and total oxidant status (TOS) and total antioxidant status (TAS) were measured in the spinal cord and sciatic nerve tissues of rats. LEC significantly reduced the glucose level of diabetic rats compared with drug control. However, MCN or anti-LY6G did not change the glucose level. While diabetic rats showed a marked decrease in both thermal and mechanical sensations, all treatments alleviated these abnormal sensations. The levels of chemokines and oxidative stress parameters increased in diabetic rats. All drug treatments significantly decreased the CCL2, CXCL1, and CXCL8 levels of spinal cord tissues and ameliorated the neuronal oxidative stress compared with control treatments. Present findings suggest that the neuroprotective actions of MCN, LEC, or anti-Ly6G treatments may be due to the modulation of neuronal oxidative stress and/or inflammatory mediators of immune cells in diabetic rats with neuropathy.
  • Küçük Resim Yok
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    Magnetic field exposure modulates the anti-inflammatory efficiency of minocycline in rats with peripheral acute inflammation
    (Innovision Communications, 2020) Mert, Tufan; Şahin, Mehmet; Şahin, Emel; Yaman, Selma
    Background and Objective . Microglial activation in spinal cord is key contributor and its inhibition by Minocycline (MCN) can result in anti-inflammatory actions. Effect of pulsed magnetic field (PMF) in living system is a very complex process and many biological and cellular processes can play key roles. In this study aimed to reveal the roles of PMF exposure on anti-inflammatory potentials of MCN treatment by evaluating the inflammatory profiles of either inflamed site or spinal cord. Methods . In this study, we investigated the anti-inflammatory effects of PMF, MCN or their combination treatments in rats with carrageenan (CG)-induced peripheral inflammation by examining the cardinal signs, hyperalgesia, allodynia, edema and fever. The levels of various inflammation markers (tumor necrosis factor-alpha), interleukin (IL)-1 beta, IL-6, IL-17, IL-4, IL-10, C-C motif chemokine ligand3 (CCL3), C-X-C motif chemokine ligand1 and myeloperoxidase were also measured in paw and spinal cord tissues. Results . CG induced inflammation caused edema, fever, and hypersensitivities. MNC or PMF treatments ameliorated these responses by suppressing pro-inflammatory markers in both inflamed paw and spinal cord. Although anti-hypersensitive, anti-edematous and anti-pyretic actions of MCN or PMF, in combined treatments PMF exposure decreased the anti-hyperalgesic and anti-allodynic actions of MCN treatment. These may be associated with decreases in IL-4 and IL-10 levels and an increase in CCL3 level of spinal cord tissues. Conclusion . Present findings support that MCN or PMF has anti-inflammatory properties duo to the down-regulating central microglial and/or peripheral inflammatory markers. Our data showed here, for the first time, PMF exposure may suppress the anti-hypersensitive actions of MCN by modulating microglia function/ phenotype and microglial markers.
  • Küçük Resim
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    Pro-inflammatory or anti-inflammatory effects of pulsed magnetic field treatments in rats with experimental acute inflammation
    (Springer Heidelberg, 2020) Mert, Tufan; Yaman, Selma
    In this study, we evaluated the possible effects of sequenced pulsed magnetic fields (PMF) of 1-mT treatments with designed different frequencies (PMF-1-1, 3, 5, 7 Hz or PMF-2-7, 9, 12, 14 Hz) on the inflammatory signs such as abnormal pain behaviors, hyperalgesia and allodynia, edema, and fever in carrageenan (CG)-induced hind paw inflammation model in rats. Paw tissues were also histologically examined. PMF exposure was applied 3 times in 24 h. CG injection gradually decreased the thermal latencies and mechanical threshold and caused significant increases in temperature and mass of paw. PMF treatments significantly reduced the temperature and mass in the paw of rats with inflammation. PMF-1 treatments caused significant increases in the latencies and thresholds. However, administration of PMF-2 treatment was significantly decreased the latency and threshold. Furthermore, the histological pieces of evidence also suggested the anti-inflammatory effects of PMF-1 treatments or inflammatory actions of PMF-2 treatments. Findings presented in this paper suggest that 1-mT PMF treatments may have anti-edematous and antipyretics activities in inflamed rats. However, the effects of PMF treatments on abnormal pain hypersensitivities may be different. PMF treatments may make inflammatory pain relief or worse in inflamed rats depending on the PMF frequencies in sequence.
  • Küçük Resim
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    Pulsed magnetic field treatment ameliorates the progression of peripheral neuropathy by modulating the neuronal oxidative stress, apoptosis and angiogenesis in a rat model of experimental diabetes
    (Taylor & Francis Ltd, 2020) Mert, Tufan; Şahin, Emel; Yaman, Selma; Şahin, Mehmet
    Objective: The present study aimed to investigate the possible anti-neuropathic effects of daily pulsed magnetic field treatments (PMF) in streptozotocin (60 mg/kg) induced 4 weeks diabetic (type-1) wistar rats (6-8 months). Materials and methods: Body mass, blood glucose and thermal and mechanical sensations were evaluated during the PMF or sham-PMF in diabetic or non-diabetic rats (n = 7/group). After the measurements of motor nerve conduction velocities (MNCV), the levels of several biomarkers for oxidative stress, apoptosis and angiogenesis in spinal cord and sciatic nerve were measured. Results: PMF for 4 weeks significantly recovered the MCNV (96.9% and 63.9%) and almost fully (100%) restored to the latency and threshold. PMF also significantly suppressed the diabetes induced enhances in biochemical markers of both neuronal tissues. Conclusions: Findings suggested that PMF might prevent the development of functional abnormalities in diabetic rats due to its anti-oxidative, anti-apoptotic and anti-angiogenic actions in neuronal tissues.