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Öğe The ameliorating effect of cannabinoid type 2 receptor activation on brain, lung, liver and heart damage in cecal ligation and puncture-induced sepsis model in rats(Elsevier, 2020) Cakir, Murat; Tekin, Suat; Okan, Asli; Cakan, Pinar; Doganyigit, ZuleyhaUncontrolled infection and increased inflammatory mediators might cause systemic inflammatory response. It is already known that Cannabinoid Type 2 (CB2) receptors, which are commonly expressed in immune cells and in many other tissues, have an effect on the regulation of immune response. In the present study of ours, the effects of CB2 receptor agonist JWH-133 was investigated on cecal ligation and puncture (CLP)-induced polymicrobial sepsis model in rats. In the present study, Sprague-Dawley rats were divided into 5 groups (i.e. the Sham, CLP, JWH-133 0.2 mg/kg, JWH-133 1 mg/kg, and JWH-133 5 mg/kg Groups). Except for the Sham Group, the CLP-induced sepsis model was applied to all groups. The histopathological damage in brain, lung, liver and, heart was examined and the caspase-3, p-NF-kappa B, TNF-alpha, IL-1 beta and IL-6 levels were determined immunohistochemically. The serum TNF-alpha, IL-1 beta, IL-6, IL-10 levels were examined with the ELISA Method. The JWH-133 treatment decreased the histopathological damage in brain, heart, lung, and liver and reduced the caspase-3, p-NF-kappa B, TNF alpha, IL-1 beta, IL-6 levels in these tissues. In addition to this, JWH-133 treatment also decreased the serum TNF-alpha, IL-1 beta, IL-6 levels, which were increased due to CLP, and increased the anti-inflammatory cytokine IL-10 levels. In the present study, it was determined that the CB2 receptor agonist JWH-133 decreases the CLP-induced inflammation, and reduces the damage in brain, lung, liver and heart. Our findings show the therapeutic potential of the activation of CB2 receptors with JWH-133 in sepsis.Öğe Cannabinoid Type 2 Receptor Activation Reduces Inflammation and Apoptosis in the Lung in Model of Sepsis Induced by Cecal Ligation Puncture(Wiley, 2019) Cakir, Murat; Tekin, Suat; Doganyigit, Zuleyha; Oflamaz, Asli Okan[Abstract Not Available]Öğe Cannabinoid type 2 receptor agonist JWH-133, attenuates Okadaic acid induced spatial memory impairment and neurodegeneration in rats(Pergamon-Elsevier Science Ltd, 2019) Cakir, Murat; Tekin, Suat; Doganyigit, Zuleyha; Erden, Yavuz; Soyturk, Merve; Cigremis, Yilmaz; Sandal, SuleymanAim: Cannabinoid system has various physiological roles such as neurogenesis, synaptic plasticity and emotional state regulation in the body. The presence of cannabinoid type 2 receptor (CB2), a member of the cannabinoid system, was detected in different regions of the brain. CB2 receptor plays a role in neuroinflammatory and neurodegenerative processes. We aimed to determine the possible effect of CB2 agonist JWH-133 in Okadaic acid (OKA)-induced neurodegeneration model mimicking Alzheimer's Disease (AD) through tau pathology. Materials and methods: In this study, 40 Sprague Dawley male rats were divided into 4 groups (Control, Sham, OKA, OKA + JWH-133). Bilateral intracerebroventricular (icv) injection of 200 ng OKA was performed in the OKA group. In the OKA + JWH-133 group, injection of JWH-133 (0.2 mg/kg) was performed intraperitoneally for 13 days different from the group of OKA. Morris water maze test was used to evaluate the spatial memory. Levels of caspase-3, phosphorylated tau (ser396), amyloid beta (A beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) levels in brain cortex; and the hippocampus regions were examined by immunohistochemical methods. Key findings: In the OKA group, caspase-3, phosphorylated tau (ser396), A beta, IL-1 beta levels were higher in the cortex and hippocampus than in the other groups. The implementation of the JWH-133 reversed the increments in these parameters, and also prevented spatial memory impairment.Öğe Effect of Cannabinoid Type 2 Receptor Activation in Okadaic Acid Induced Rat Alzheimer's Disease Model(Wiley, 2018) Cakir, Murat; Doganyigit, Zuleyha; Tekin, Suat; Erden, Yavuz; Cigremis, Yilmaz; Sandal, Suleyman[Abstract Not Available]Öğe The protective effect of cannabinoid type 2 receptor activation on renal ischemia-reperfusion injury(Springer, 2019) Cakir, Murat; Tekin, Suat; Doganyigit, Zuleyha; Cakan, Pinar; Kaymak, EminKidney ischemia reperfusion (IR) injury is an important health problem resulting in acute renal failure. After IR, the inflammatory and apoptotic process is triggered. The relation of Cannabinoid type 2 (CB2) receptor with inflammatory and apoptotic process has been determined. The CB2 receptor has been shown to be localized in glomeruli and tubules in human and rat kidney. Activation of CB2 receptor with JWH-133 has been shown to reduce apoptosis and inflammation. In this study, it was investigated whether CB2 activation with selective CB2 receptor agonist JWH-133 was protective against renal IR injury. Male Sprague-Dawley rats were divided into 5 groups (n=45). Bilateral ischemia was treated to the IR group rat's kidneys for 45 min and then reperfusion was performed for 24 h. Three different doses of JWH-133 (0.2, 1 and 5 mg/kg) were administered to the treatment groups at the onset of ischemia. The JWH-133 application at three different doses decreased the glomerular and tubular damage. Additionally, in the renal tissue, nuclear factor-kappa B, tumour necrosis factor alpha, interleukin-1beta, and caspase-3 levels decreased immunohistochemically. Similarly, JWH-133 application decreased the serum tumour necrosis factor alpha, blood urea nitrogen, creatinine, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, Cystatin C, interleukin-18, interleukin-1beta, interleukin-6, and interleukin-10 levels. We found that JWH-133 and CB2 receptor activation had a curative effect against kidney IR damage. JWH-133 may be a new therapeutic agent in preventing kidney IR damage.
