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AIM: Cardiac damage caused by radiation in the long term varies according to the radiation dose received by the heart. In this study, it was aimed to evaluate the damage caused by different radiation doses in the heart, together with hemodynamic parameters, immunhistochemistry, and histopathological analyzes for long term. METHOD AND MATERIALS: The animals were divided into four groups: The rats in control group (Group 1) were not irradiated; the rats in group 2 were irradiated with 5 Gy; the rats in group 3 were irradiated with 10 Gy and the rats in group 4 were irradiated with 20 Gy. Hemodynamic parameters and indices were determined from the impedance cardiography (ICG) recording in the whole groups before they were irradiated with RT and 180 days after RT. And then, interleukin-1ß, interleukin-10, TNF-α, apopthosis were determined in all groups. In addition, histological changes of heart and aorta were evaluated. RESULTS: Histopathologic, cytokine and hemodynamic findings supported that cardiac damage increased with increasing radiation dose. CONCLUSION: it is important in terms of being an alternative and supportive method to other methods to be able to detect heart diseases caused by RT with the ICG method.
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Cardiografía de Impedancia , Oncología por Radiación , Ratas , Animales , Impedancia Eléctrica , CorazónRESUMEN
INTRODUCTION: We aimed to investigate the efficacy of local boric acid (BA) and teicoplanin in prosthetic vascular graft infection (PVGI) caused by methicillin-resistant Staphylococcus aureus (MRSA) in a rat model. METHODOLOGY: Fourty rats were divided into five groups. Group 1 received no treatments (control group); group 2 was uncontaminated polytetrafluoroethylene (PTFE) graft group; group 3 was untreated and the PTFE graft was contaminated with 2×107 CFU/mL MRSA; group 4 received local BA (8 mg/kg) and was contaminated with with 2×107 CFU/mL MRSA; group 5 received local BA (8 mg/kg) and intraperitoneal teikoplanin (10 mg/kg), and was contaminated with 2×107 CFU/mL MRSA; On the 3rd day, grafts and serums were removed for microbiological, histological and serological tests. RESULTS: The amounts of culture growth in groups 4 and 5 were significantly lower compared to group 3 (p < 0.001). TNF-α was significantly higher in Group 3 than the other groups (p = 0.001). There was no significant difference between the groups in serum IL-1 levels (p = 0.138). Monocyte chemotactic protein-1 (MCP-1) was not significantly different between groups 3, 4, and 5, but it was significantly higher than groups 1 and 2 (p < 0.001). The severity of inflammation was significantly higher in group 3 than the other groups, and fibroblastic proliferation, granulation tissue and collagen synthesis were significantly lower (p < 0.05). CONCLUSIONS: Our study showed that local BA and combined teicoplanin treatment is effective in preventing PVGI.
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Staphylococcus aureus Resistente a Meticilina , Infecciones de los Tejidos Blandos , Infecciones Estafilocócicas , Ratas , Animales , Teicoplanina/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Prótesis Vascular/efectos adversos , Prótesis Vascular/microbiología , Politetrafluoroetileno , Antibacterianos/uso terapéuticoRESUMEN
This study aimed to establish the relationship between two endoplasmic reticulum (ER) stress proteins, glucose-regulated protein 78 (GRP78/BiP) and PKR-like endoplasmic reticulum kinase (PERK), and oxidative stress markers in cisplatin (CIS)-induced and gentamicin (GEN)-induced nephrotoxicity.The study consisted of five groups: control (saline solution only), CIS D2 (2.5 mg/kg for 2 days), CIS D7 (2.5 mg/kg for 7 days), GEN D2 (160 mg/kg for 2 days), and GEN D7 (160 mg/kg for 7 days). All rats were sacrificed 24 h after the last injection for standard clinical chemistry, and ultrastructural and histological evaluation of the kidney.CIS and GEN increased blood urea nitrogen (BUN) and serum creatinine (Cr) levels, as well as total oxidant status (TOS), while decreasing total antioxidant status (TAS) level in CIS D7 and GEN D7 groups. Histopathological and ultrastructural findings were also consistent with renal tubular damage. In addition, expression of markers of renal inflammation (tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß)) and ER stress markers (GRP78 and PERK) was significantly increased in the kidney tissue of rats treated with CIS and GEN for 7 days.These findings suggest that CIS and GEN administration for 7 days aggravates nephrotoxicity through the enhancement of oxidative stress, inflammation, and ER stress-related markers. As a result, the recommended course of action is to utilize CIS and GEN as an immediate but brief induction therapy, stopping after 3 days and switching to other drugs instead.
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Cisplatino , Chaperón BiP del Retículo Endoplásmico , Animales , Ratas , Cisplatino/toxicidad , Retículo Endoplásmico , Gentamicinas/toxicidad , Gentamicinas/metabolismo , Inflamación/tratamiento farmacológico , Riñón , Estrés Oxidativo , Estrés del Retículo EndoplásmicoRESUMEN
To assess the potential therapeutic role of antilipidemic ezetimibe on endometriosis in an experimental rat model. A standard experimental endometriosis model was created with 18 Whistar-Albino rats, and after 1 month, the sizes of the endometriotic explants were measured. The rats were randomized as study and control groups. A total of 1 mg/kg/day ezetimibe and 1 ml/kg/day saline were administered orally to the study and control groups respectively for 28 days. At the end of 28 days, the explants were measured again, excised, and sent for histopathologic assessment for expression of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) and number of mast cells. At the end of the study period, the size of the endometriotic explants decreased significantly in the study group; but not in the control group (from 145.3 ± 120.5 to 89.8 ± 60.1 vs 174.72 ± 88.3 to 87.65 ± 27.1 cm3 respectively); however, the amount of post- and pretreatment differences in explant sizes was similar in the groups. The median TNF-α and VEGF levels were significantly lower in the ezetimibe group when compared to the control group (4 [3-4] vs 2 [1-3], p 0.029; 4 [3-4] vs 2 [2-3], p 0.002; respectively). And numbers of mast cells in all uterine layers were also lower in the ezetimibe group. Ezetimibe decreased the size of the endometriotic explants with its anti-inflammatory and anti-angiogenic properties. This agent alone or with combination of other agents may have a potential role in the treatment of endometriosis.
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Endometriosis , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Modelos Animales de Enfermedad , Endometriosis/tratamiento farmacológico , Endometriosis/metabolismo , Endometriosis/patología , Ezetimiba/farmacología , Ezetimiba/uso terapéutico , Femenino , Humanos , Ratas , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Difficulty in the clinical practice of stem cell therapy is often experienced in achieving desired target tissue cell differentiation and migration of stem cells to other tissue compartments where they are destroyed or die. This study was performed to evaluate if mesenchymal stem cells (MSCs) may differentiate into desired cell types when injected after combined with an injectable cryogel scaffold and to investigate if this scaffold may help in preventing cells from passing into different tissue compartments. MSCs were obtained from fat tissue of the rabbits as autografts and nuclei and cytoplasms of these cells were labeled with BrdU and PKH26. In Group 1, only-scaffold; in Group 2, only-MSCs; and in Group 3, combined stem cell/scaffold were injected to the right malar area of the rabbits. At postoperative 3 weeks, volumes of the injected areas were calculated by computer-tomography scans and histopathological evaluation was performed. The increase in the volume of the right malar areas was more in Group 3. In histopathological evaluation, chitosan cryogel microspheres were observed microscopically within the tissue and the scaffold was only partially degraded. Normal tissue form was seen in Group 2. Cells differentiated morphologically into fat cells were detected in Groups 2 and 3. Injectable chitosan cryogel microspheres were used in vivo for the first time in this study. As it was demonstrated to be useful in carrying MSCs to the reconstructed area, help cell differentiation to desired cells and prevent migration to other tissue compartments, it may be used for reconstructive purposes in the future.
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Quitosano , Células Madre Mesenquimatosas , Adipocitos , Animales , Diferenciación Celular , Proliferación Celular , Criogeles , Conejos , Ingeniería de Tejidos/métodos , Andamios del TejidoRESUMEN
PURPOSE: Rapid development in mobile phone technologies increase the average mobile phone usage duration. This increase also triggers exposure to radiofrequency radiation (RF), which is a risk factor for the health. In this study, it was aimed to investigate the effect of mobile phone working with LTE-Advanced Pro (4.5 G) mobile network on the optic nerve, which is responsible for the transmission of visual information. MATERIAL AND METHODS: Thirty-two rats divided into two groups as control (no RF, sham exposure) and experimental (RF exposure using a mobile phone with LTE-Advanced Pro network; 2 hours/day, 6 weeks). The visual evoked potential (VEP) was recorded and determined amplitudes and latencies of VEP waves. Optic nerve malondialdehyde level, catalase and superoxide dismutase activities were determined. Furthermore, ultrastructural and morphometric changes of optic nerve were evaluated. RESULTS: In VEP recordings, the mean VEP amplitudes of experimental group were significantly lower than control group. In ultrastructural evaluation, myelinated nerve fibres and glial cells were observed in normal histologic appearance both in sham and experimental group. However, by performing morphometric analysis, in the experimental group, axonal diameter and myelin thickness were shown to be lower and the G-ratio was higher than in the sham group. In the experimental group, malondialdehyde level was significantly higher and superoxide dismutase and catalase activities were significantly lower than sham group. There was a high correlation between VEP wave amplitudes and oxidative stress markers. CONCLUSION: Findings obtained in this study support optic nerve damage. These results point out an important risk that may decrease the quality of life.
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Teléfono Celular , Traumatismos del Nervio Óptico/etiología , Nervio Óptico/efectos de la radiación , Ondas de Radio/efectos adversos , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta en la Radiación , Potenciales Evocados Visuales/efectos de la radiación , Humanos , Masculino , Nervio Óptico/patología , Traumatismos del Nervio Óptico/patología , Estrés Oxidativo/efectos de la radiación , RatasRESUMEN
It has been clearly indicated that osteoarthritis (OA) is an inflammatory and degenerative disease that could be promoted by Rho-kinase (ROCK); however, little is known about the role of ROCK/inhibitor κB alpha (IκB-α)/nuclear factor-κB (NF-κB) p65 pathway activation in interleukin-1ß (IL-1ß) induced inflammatory response and oxidative stress in primary human chondrocytes. To test this hypothesis, we focused on determining ROCK-II, IκB-α, p-IκB-α, NF-κB p65, p-NF-κB p65, IL-6, tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), p22phox, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subtype 4 (NOX4) protein expression, ROCK-II activity, NADPH oxidase levels, and total antioxidant capacity (TAC) in the presence and absence of ROCK-inhibitor fasudil. IL-1ß (2 ng·mL-1, 24 h) increased the expression of ROCK-II, p-IκB-α, NF-κB p65, p-NF-κB p65, IL-6, TNF-α, COX-2, and p22phox proteins, and decreased the expression of IκB-α, and the NOX4 protein level did not alter. ROCK activity and NADPH oxidase levels were increased, whereas the TAC was decreased by IL-1ß. Fasudil (10-5-10-7 M) reversed all these changes induced by IL-1ß. These results demonstrate that ROCK/IκB-α/NF-κB p65 pathway activation contributes to the IL-1ß-induced inflammatory response and oxidative stress, and thus, ROCK inhibition might be a beneficial treatment option for OA patients mainly based on its anti-inflammatory and antioxidant effects.
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Condrocitos/efectos de los fármacos , Condrocitos/patología , Interleucina-1beta/farmacología , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/metabolismo , Quinasas Asociadas a rho/metabolismo , Condrocitos/metabolismo , HumanosRESUMEN
PURPOSE: Ischemia-reperfusion (I-R) injury is a serious problem caused by vascular trauma, tourniquet use and/or compartment syndrome. Studies have reported that skeletal muscle function is impaired due to the lower extremity I-R injury. There are insufficient studies on the treatment methods used for the recovery of dysfunction. This study is designed to investigate the effects of trans-cinnamaldehyde (TCA), a volatile oil of cinnamon structure, on the contractile dysfunction due to I-R injury of rat extensor-digitorum-longus (EDL) muscle. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into three groups. Except for the animals in the control group, all animals received saline (3-ml/kg) or TCA solution (30-mg/kg) which was administered orally three times with an 8-h interval before ischemia. After 24-hours, experimental groups were subjected to 3-h of lower extremity ischemia followed by 5-h reperfusion period. Then, the compound muscle action potential (CMAP) and mechanical activity of muscle were recorded using the standard electro-biophysical techniques. RESULTS: There was a decrease in the maximum contractile force in I-R group compared to the control group (p < 0.05). Oxidative damage indicator (MDA) and antioxidant indicator (CAT) increased in the EDL muscle and serum samples in the I-R group (p < 0.05). Laminin expression showed a reduction in the I-R group (p < 0.05). It was seen that TCA achieve again the maximum contraction force in the EDL muscle (p < 0.05) and maintain the expression of laminin (p > 0.05). CONCLUSION: We concluded that TCA has a potential protective effect with antioxidant effects against I-R injury and may maintain laminin levels.
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Laminina , Daño por Reperfusión , Acroleína/análogos & derivados , Animales , Isquemia/tratamiento farmacológico , Músculo Esquelético , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/etiología , Daño por Reperfusión/prevención & controlRESUMEN
This study aimed to determine the expression of nuclear factor kappa B (NF-κB) pathway related miRNAs in experimental acute respiratory distress syndrome (ARDS) induced by lipopolysaccharide (LPS) in rats, and to elucidate the underlying molecular mechanism. Twenty four sprague dawley rats were randomly divided into two groups; LPS (n = 12) and control (n = 12). Experimental ARDS was induced by intraperitoneal injection of E. coli LPS in LPS group. Intraperitoneal saline was administered in control group. Serum and lung samples were collected from both groups. Immunohistochemistry staining was performed for interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), CD 68, and caspase-3 in lung samples. Intensity of staining was scored as strong, moderate, weak, and no for evaluation of IL-1ß and TNF-α. In addition, caspase-3 and CD68-positive stained cells were counted in sections. Expressions of 9 miRNAs were determined by quantitative real-time PCR in serum samples. IL-1ß and TNF-α staining scores were significantly higher in the LPS group in comparison with the control group (P = 0.04 and P = 0.02, respectively). In addition, caspase-3 and CD68-positive stained cells were significantly higher in the LPS group (P = 0.02). Expressions of seven miRNAs were significantly changed in the LPS group in comparison with the control group. While six miRNAs (miR-7a-5p, miR-7b, miR-9a-5p, miR-21-5p, miR-29a-3p, and miR-138-5p) were up regulated, only miR-124-3p was down regulated. This study suggests that these miRNAs may have a role in the pathogenesis of ARDS related to NF-κB. However, this relationship needs to be examined in new studies by evaluation of pathways and target genes.
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OBJECTIVE: We aimed to investigate the protective effect of adrenomedullin (ADM) on cerebral tissue of rats with cerebral ischemia/reperfusion (I/R) injury. METHODS: Thirty-two Wistar rats were randomized into four groups (n=8). In the I/R Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, reperfused for 120 minutes. In the ADM Group, rats received 12 µg/kg of ADM. In the I/R+ADM Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, the rats received 12 µg/ kg of ADM. Then, reperfusion was performed for 120 minutes. The Control Group underwent no procedure. Blood and brain tissue samples were collected for biochemical and histopathological analysis. Serum malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were analysed. Brain tissue was evaluated histopathologically and neuronal cells were counted in five different fields, at a magnification of ×400. RESULTS: Brain MDA in I/R Group was significantly higher than in ADM Group. Brain GPx and SOD in I/R+ADM Group were significantly higher than in I/R Group. The number of neurons was decreased in I/R Group compared to the Control Group. The number of neurons in I/R+ADM Group was significantly higher than in I/R Group, and lower than in Control Group. Apoptotic changes decreased significantly in I/R+ADM Group and the cell structure was similar in morphology compared to the Control Group. CONCLUSION: We demonstrated the cerebral protective effect of ADM in the rat model of cerebral I/R injury after bilateral carotid artery occlusion.
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Arteria Carótida Común , Adrenomedulina , Animales , Ratas , Ratas Wistar , Reperfusión , Daño por Reperfusión/prevención & controlRESUMEN
Abstract Objective: We aimed to investigate the protective effect of adrenomedullin (ADM) on cerebral tissue of rats with cerebral ischemia/reperfusion (I/R) injury. Methods: Thirty-two Wistar rats were randomized into four groups (n=8). In the I/R Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, reperfused for 120 minutes. In the ADM Group, rats received 12 µg/kg of ADM. In the I/R+ADM Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, the rats received 12 µg/ kg of ADM. Then, reperfusion was performed for 120 minutes. The Control Group underwent no procedure. Blood and brain tissue samples were collected for biochemical and histopathological analysis. Serum malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were analysed. Brain tissue was evaluated histopathologically and neuronal cells were counted in five different fields, at a magnification of ×400. Results: Brain MDA in I/R Group was significantly higher than in ADM Group. Brain GPx and SOD in I/R+ADM Group were significantly higher than in I/R Group. The number of neurons was decreased in I/R Group compared to the Control Group. The number of neurons in I/R+ADM Group was significantly higher than in I/R Group, and lower than in Control Group. Apoptotic changes decreased significantly in I/R+ADM Group and the cell structure was similar in morphology compared to the Control Group. Conclusion: We demonstrated the cerebral protective effect of ADM in the rat model of cerebral I/R injury after bilateral carotid artery occlusion.
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Animales , Ratas , Arteria Carótida Común , Reperfusión , Daño por Reperfusión/prevención & control , Ratas Wistar , AdrenomedulinaRESUMEN
The aim of the present study was to systematically investigate the effects of chronic exposure to extremely low-frequency electromagnetic field (ELF-EMF) on electrophysiological, histological and biochemical properties of the diaphragm muscle in rats. Twenty-nine newly weaned (24 days old, 23-80 g) female (n = 15) and male (n = 14) Wistar Albino rats were used in this study. The animals were randomly divided into two groups: the control group and the electromagnetic field (EMF) group. The control group was also randomly divided into two groups: the control female group and the control male group. The EMF exposure group was also randomly divided into two groups: the ELF-EMF female group and the ELF-EMF male group. The rats in the ELF-EMF groups were exposed for 4 h daily for up to 7 months to 50 Hz frequency, 1.5 mT magnetic flux density. Under these experimental conditions, electrophysiological parameters (muscle bioelectrical activity parameters: intracellular action potential and resting membrane potential and muscle mechanical activity parameter: force-frequency relationship), biochemical parameters (Na+, K+, Cl- and Ca+2 levels in the blood serum of rats; Na+-K+ ATPase enzyme-specific activities in muscle tissue; and free radical metabolism in both muscle tissue and serum) and transmission electron microscopic morphometric parameters of the diaphragm muscle were determined. We found that chronic exposure to ELF-EMF had no significant effect on the histological structure and mechanical activity of the muscle and on the majority of muscle bioelectrical activity parameters, with the exception of some parameters of muscle bioelectrical activity. However, the changes in some bioelectrical activity parameters were relatively small and unlikely to be clinically relevant.
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Diafragma/efectos de la radiación , Campos Electromagnéticos/efectos adversos , Músculo Esquelético/efectos de la radiación , Animales , Diafragma/patología , Femenino , Masculino , Músculo Esquelético/patología , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Purpose: Although radiotherapy (RT) is an important component of cancer treatment, it induces adverse tissue reactions in the around of cancer tissue. Therefore, radioprotectives are needed to protect normal tissues. The aim of this study was to investigate the radioprotective effect of N-acetylcysteine (NAC) on RT-induced cardiac damage in rats for the acute term.Materials and methods: The animals were divided into four groups. The rats in control group were injected with saline for 7 d; the rats in NAC group were injected NAC at dose of 240 mg/kg d for 7 d; the rats in RT group were injected with saline for 7 d plus was irradiated 1 h after the last injection and the rats in NAC + RT group were injected with NAC for 7 d and irradiated 1 h after the last NAC dose. The electrocardiogram was recorded and evaluated PR interval, QRS duration, QT interval, T wave alterations and heart rate. Serum interleukin-4, interleukin-6, tumor necrosis factor-alpha, interleukin 1 beta, galectin-3 levels and creatine kinase and creatine kinase isoenzyme-MB activities were determined in all groups. Also, tissue malondialdehyde (MDA) and nitric oxide levels, superoxide dismutase, catalase and glutathione peroxidase activities were determined. In addition, histological changes of heart were evaluated. All measurements were performed 24 h after RT.Results: In the RT group, findings supporting cardiac injury were observed in the electrocardiogram. Also, cytokine levels and oxidative stress were significantly increased. Pretreatment of rats with NAC ameliorated cardiac injury induced by RT.Conclusions: Our findings suggested that NAC may be a potential radioprotector which is capable of preventing cardiac damage.