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Arterias Mamarias , Vena Safena , Sugammadex , Humanos , Sugammadex/administración & dosificación , Sugammadex/farmacología , Vena Safena/efectos de los fármacos , Arterias Mamarias/efectos de los fármacos , gamma-Ciclodextrinas/administración & dosificación , gamma-Ciclodextrinas/farmacología , MasculinoRESUMEN
BACKGROUND: The aim of this study is to investigate the effect of trimethylamine (TMA) and trimethylamine-n-oxide (TMAO) on the contractility of human umbilical artery and the possible mechanisms involved. METHODS: Vasoactive responses to TMA and TMAO on human umbilical artery rings were measured in isolated organ baths. Cumulative dose-response curves for TMA and TMAO were obtained before and after incubation with atropine, yohimbine, prazosin, indomethacin, verapamil, and Ca+2 -free Krebs-Henselite solution. RESULTS: Administration of cumulative TMA and TMAO resulted in dose-dependent contraction at concentrations ranging from 10 to 100 mM on human umbilical artery rings. TMA-induced contractions were more potent than TMAO-induced contractions (TMA: -logEC50 = 1.00 ± 0.02, TMAO: -logEC50 = 0.57 ± 0.02). Contraction responses to TMA were significantly lower in the presence of verapamil and in the absence of external Ca+2 (p < 0.001, p < 0.05, respectively). CONCLUSION: Our results showed that TMA and TMAO caused vasoconstriction in isolated human umbilical artery rings. Our findings also indicated that TMA but not TMAO-induced vasoconstriction was partially dependent on extracellular Ca2+ and calcium influx through L-type Ca2+ channels. Our results suggest that TMA and TMAO may have the potential to contribute to cardiovascular diseases through their direct effect on vascular contractility in human arteries.
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Metilaminas , Arterias Umbilicales , Humanos , Metilaminas/administración & dosificación , Metilaminas/farmacología , Óxidos , Arterias Umbilicales/efectos de los fármacosRESUMEN
BACKGROUND AND OBJECTIVE: Arachidonic acid (ARA) is essential for the fluidity, selective permeability, and flexibility of the cell membrane. It is an important factor for the function of all cells, particularly in the nervous system, immune system, and vascular endothelium. ARA is the second most common polyunsaturated fatty acid in the phospholipids of the nerve cell membrane after docosahexaenoic acid. ARA metabolites have many kinds of physiologic roles. The major action of ARA metabolites is the promotion of the acute inflammatory response, mediated by the production of pro-inflammatory mediators such as PGE2 and PGI2, followed by the formation of lipid mediators, which have pro-resolving effects. Another important action of ARA derivatives, especially COX, is the regulation of vascular reactivity through PGs and TXA2. There is significant involvement of ARA metabolites in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and neuropsychiatric disorders. ARA derivatives also make an important contribution to acute stroke, global ischemia, subarachnoid hemorrhage, and anticoagulation-related hemorrhagic transformation. CONCLUSION: In this review, we have discussed experimental and human study results of neurologic disorders related to ARA and its metabolites in line with treatment options.
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Ácido Araquidónico/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Enfermedad de Alzheimer/metabolismo , Animales , Ácidos Docosahexaenoicos/metabolismo , Humanos , Inflamación/metabolismo , Enfermedad de Parkinson/metabolismoRESUMEN
Dexmedetomidine is a selective α2-adrenoceptor agonist that is used because of its sedative, anxiolytic, and analgesic effects. Dexketoprofen, which is used as an analgesic, is a nonselective nonsteroidal anti-inflammatory drug (NSAID). The use of dexmedetomidine and dexketoprofen as adjuvants to local anesthetics for the peripheral nerve is gradually increasing. In this study, we aimed to investigate the effects of different doses of dexmedetomidine and dexketoprofen on conduction block of rat sciatic nerve. The isolated sciatic nerve from adult rats was transferred to a nerve chamber. The compound action potentials (CAPs) were recorded from stimulated nerve with electrophysiological methods. Dexmedetomidine (n = 8) and dexketoprofen (n = 8) were administered in the chamber with cumulative concentrations of 10-9 to 10-5 M, and the CAPs were recorded for 5 and 10 minutes. The CAP parameters were calculated. Both dexmedetomidine and dexketoprofen significantly depressed all CAP parameters in a dose-dependent manner compared with the control group, i.e., the group in which rats did not receive treatment. CAP parameters showed there was no significant difference in nerve conduction inhibition between dexmedetomidine and dexketoprofen. Higher doses of dexmedetomidine suppressed the conduction in the fast-conducting fibers; however, dexketoprofen was found to suppress the conduction in the slow-conducting fibers in a time-dependent manner and suppress the conduction in the medium- and slow-conducting fibers in a dose-dependent manner. These findings suggest that dexmedetomidine and dexketoprofen exhibit better anesthetic effects on peripheral nerve through different ways of action. The experimental procedures were approved by the Necmettin Erbakan University on January 30, 2013 (approval No. 2013-024).
RESUMEN
Carvacrol (CRV) has strong cytoprotective, antioxidant, and anti-inflammatory properties. We aimed to demonstrate the possible protective effects of CRV on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Wistar rats were allocated into the following four groups: Sham, CLP, Sham + CRV, and CLP + CRV. The animals were orally administered with CRV (80 mg/kg/day) or vehicle (corn oil; 1 mL/kg/day) for 7 days. At the eighth day, Sham or CLP procedure was applied. Twenty hours after the operations, MBF and contractile responses of isolated aortic preparations to phenylephrine were measured. Tissue samples were obtained for biochemical and histopathological assessments. Additionally, survival rates were recorded throughout 96 h. CRV administration improved the mesenteric perfusion, contractile function of aorta, and survival after CLP. CRV substantially prevented the elevations in the levels of LDH, BUN, Cr, and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) but could not prevent the elevations of AST and ALT after CLP. The decreased liver, kidney, and spleen glutathione levels and increased liver, kidney, lung, and spleen malondialdehyde levels induced by CLP were substantially restored by CRV. Also, histopathological protective effects of CRV on multiple organ damage due to CLP were observed. CRV possesses strong ameliorative effects on sepsis due to its protective effects on mesenteric perfusion and aortic function and its antioxidative and anti-inflammatory effects.
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Aorta/efectos de los fármacos , Monoterpenos/farmacología , Sepsis/tratamiento farmacológico , Animales , Antiinflamatorios , Antioxidantes , Aorta/fisiología , Cimenos , Mesenterio/efectos de los fármacos , Monoterpenos/uso terapéutico , Insuficiencia Multiorgánica/tratamiento farmacológico , Ratas , Ratas Wistar , Sepsis/microbiologíaRESUMEN
BACKGROUND: Coenzyme Q10 (CoQ10) is a naturally occurring, lipid-soluble antioxidant and an essential electron carrier in the mitochondrial respiratory chain. In sepsis, CoQ10 deficiency induced by mitochondrial failure can lead to hypoxia, hypoperfusion, oxidative organ damage and finally death. We aimed to investigate the effects of CoQ10 on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis. METHODS: Wistar rats were divided into Sham, CLP, Sham+CoQ10, CLP+CoQ10 subgroups. CoQ10 (10mg/kg/day) or vehicle (olive oil; 1mL/kg/day) was intraperitoneally injected for 15days. At 16th day, Sham or CLP operation was performed. 20h after the operations, MABF and phenylephrine responses of isolated aortic rings were measured. Tissue samples were obtained for histopathological and biochemical evaluations. Furthermore, survival rates were monitored throughout 96h. RESULTS: CoQ10 prevented mesenteric hypoperfusion and aortic dysfunction induced by CLP. Survival rate was %0 at 46th h in CLP group, but in CLP+CoQ10 group it was 37.5% at the end of 96h. CLP-induced elevations of serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were blocked by CoQ10. CoQ10 restored the increased liver, lung, spleen and kidney malondialdehyde levels and as well as reduced liver and spleen glutathione levels. The protective effects of CoQ10 on multiple organ damage were also observed histopathologically. CONCLUSIONS: CoQ10 showed protective effects in sepsis due to its preservative effects on mesenteric perfusion, aortic function and also its anti-inflammatory and antioxidative effects.
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Isquemia Mesentérica/tratamiento farmacológico , Sepsis/tratamiento farmacológico , Ubiquinona/análogos & derivados , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Ciego/efectos de los fármacos , Ciego/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Ligadura/métodos , Malondialdehído/metabolismo , Isquemia Mesentérica/metabolismo , Sustancias Protectoras/farmacología , Ratas , Ratas Wistar , Circulación Renal/efectos de los fármacos , Sepsis/metabolismo , Tasa de Supervivencia , Ubiquinona/farmacologíaRESUMEN
Tumor necrosis factor-alpha (TNF-α) is a pivotal mediator that triggers inflammatory process, oxidative stress, and multiple organ injury in sepsis. We investigated the effects of infliximab on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis. Wistar rats were divided into Sham, CLP, Sham+infliximab, and CLP+infliximab subgroups. Twenty-four hours before the operations, rats were injected intraperitoneally with infliximab (7 mg/kg) or vehicle (saline; 1 mL/kg). Twenty hours after the operations, MBF and phenylephrine responses of isolated aortic rings were measured. Tissue damages were examined biochemically and histopathologically. Furthermore, survival rates were monitored throughout 96 h. Infliximab improved survival, mesenteric perfusion, and aortic function after CLP. Increases of serum AST, ALT, LDH, BUN, Cr, and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) induced by CLP were blocked by infliximab. Infliximab prevented malondialdehyde elevations in septic liver, lung, spleen, and kidney tissues, as well as glutathione reductions in septic liver, spleen, and kidney tissues. Protective effects of infliximab on multiple organ damage were also observed histopathologically. Infliximab showed protective effects in sepsis due to its improvement effects on mesenteric perfusion, aortic function, and its anti-inflammatory and antioxidative effects.
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Aorta/efectos de los fármacos , Circulación Sanguínea/efectos de los fármacos , Infliximab/farmacología , Mesenterio/irrigación sanguínea , Insuficiencia Multiorgánica/complicaciones , Sepsis/mortalidad , Sepsis/fisiopatología , Animales , Aorta/fisiopatología , Femenino , Interleucina-6/metabolismo , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiopatología , Ratas , Ratas Wistar , Sepsis/complicaciones , Sepsis/patologíaRESUMEN
BACKGROUND: Thymoquinone (TQ) is a potent cytoprotective, antioxidant and anti-inflammatory agent. We aimed to investigate the possible protective effects of TQ on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in a murine sepsis model induced by cecal ligation and puncture (CLP). METHODS: Wistar rats were divided into the following four groups: Sham, CLP, Sham+TQ and CLP+TQ. TQ (1mg/kg/day) or vehicle (dimethyl sulfoxide, 1mL/kg/day) was intraperitoneally injected for 3 days. At 4th day Sham or CLP operation was applied. 20h after the operations, MABF and contractile responses of isolated aortic rings to phenylephrine were measured. Tissue samples were obtained for histopathological and biochemical examinations. Also, survival rates were recorded throughout 96h. RESULTS: TQ ameliorated mesenteric hypoperfusion and partially attenuated aortic dysfunction induced by CLP. Survival rate was %0 at 42nd h in CLP group, but in CLP+TQ group it was 33.4% at the end of 96h. Serum levels of AST, ALT, LDH, BUN, Cr and inflammatory cytokines (tumor necrosis factor-α, interleukin-1 ß and interleukin-6) increased in CLP group that were prevented by TQ. The decreases in liver, spleen and kidney glutathione levels and the increases in liver, lung, kidney and spleen malondialdehyde levels induced by CLP were inhibited by TQ. The histopathological protective effects of TQ on multiple organ damage due to CLP were also observed. CONCLUSION: TQ has ameliorative effects on sepsis due to its protective effects on mesenteric perfusion, contractile function of aorta and its anti-inflammatory and antioxidative effects.
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Aorta/efectos de los fármacos , Benzoquinonas/uso terapéutico , Isquemia Mesentérica/prevención & control , Insuficiencia Multiorgánica/prevención & control , Sepsis/complicaciones , Sepsis/mortalidad , Animales , Benzoquinonas/química , Femenino , Estructura Molecular , Insuficiencia Multiorgánica/patología , Distribución Aleatoria , Ratas , Ratas Wistar , Sepsis/patología , Análisis de SupervivenciaRESUMEN
BACKGROUND: The cyclooxygenase (COX)-2 overexpression is associated with vascular injury and multiple organ failure in sepsis. However, constitutive COX-1 and basal COX-2 expressions have physiological effects. We aimed to investigate the effects of partial and selective COX-2 inhibition without affecting constitutive COX-1 and basal COX-2 activities by celecoxib on mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries, and survival in septic rats accomplished by cecal ligation and puncture (CLP). METHODS: Wistar rats were allocated into Sham, CLP, Sham+celecoxib, CLP+celecoxib subgroups. 2h after Sham and CLP operations, celecoxib (0.5mg/kg) or vehicle (saline; 1mL/kg) was administered orally to rats. 18h after drug administrations, MABF and responses of isolated aortic rings to phenylephrine were measured. Tissue samples were obtained for biochemical and histopathological examinations. Furthermore, survival rate was monitored throughout 96h. RESULTS: Celecoxib ameliorated mesenteric hypoperfusion and partially improved aortic dysfunction induced by CLP. Survival rate was%0 at 49th h in CLP group, but in CLP+celecoxib group it was 42.8% at the end of 96h. Serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were increased in CLP group that were prevented by celecoxib. The decreases in liver and spleen glutathione levels and the increases in liver, lung, spleen and kidney malondialdehyde levels in CLP group were blocked by celecoxib. The histopathological protective effects of celecoxib on organ injury due to CLP were also observed. CONCLUSIONS: Celecoxib has protective effects on sepsis due to its preservative effects on mesenteric perfusion, aortic function and its anti-inflammatory and antioxidative effects.
Asunto(s)
Aorta/efectos de los fármacos , Enfermedades de la Aorta/tratamiento farmacológico , Celecoxib/farmacología , Isquemia Mesentérica/tratamiento farmacológico , Insuficiencia Multiorgánica/tratamiento farmacológico , Sepsis/tratamiento farmacológico , Animales , Aorta/metabolismo , Enfermedades de la Aorta/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Glutatión/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Malondialdehído/metabolismo , Isquemia Mesentérica/metabolismo , Insuficiencia Multiorgánica/metabolismo , Ratas , Ratas Wistar , Sepsis/metabolismo , Tasa de SupervivenciaRESUMEN
This study was designed to investigate whether dexketoprofen added to perineuraly or subcutaneously alters the effects of levobupivacaine in a rat model of sciatic nerve blockade. Thirty-six rats received unilateral sciatic nerve blocks along with a subcutaneous injection by a blinded investigator assigned at random. Combinations were as follows: Group 1 (sham) perineural and subcutaneous saline; Group 2, perineural levobupivacaine alone and subcutaneous saline; Group 3, perineural levobupivacaine plus dexketoprofen and subcutaneous saline; Group 4, perineural levobupivacaine and subcutaneous dexketoprofen; Group 5, perineural dexketoprofen and subcutaneous saline; and Group 6, perineural saline and subcutaneous dexketoprofen. The levobupivacaine concentration was fixed at 0.05%, and the dose of dexketoprofen was 1 mg kg(-1) . Sensory analgesia was assessed by paw withdrawal latency to a thermal stimulus every 30 min. The unblocked paw served as the control for the assessment of systemic, centrally mediated analgesia. Perineural and subcutaneous dexketoprofen coadministered with perineural levobupivacaine did not enhance the duration of sensory blockade when compared with levobupivacaine alone. There were significant differences between the operative and control paws for time points 30-90 min in the perineural levobupivacaine alone, levobupivacaine + dexketoprofen and subcutaneous dexketoprofen added levobupivacaine group. Significant differences were not determined between the levobupivacaine alone group and dexketoprofen added groups in operative paw. The effects of dexketoprofen are unknown for perineural administration. There is no significant difference between the analgesic effects of peripheral nerve blocks using levobupivacaine alone and plus subcutaneous or perineural dexketoprofen.
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Analgesia/métodos , Anestésicos Locales/farmacología , Antiinflamatorios no Esteroideos/farmacología , Bloqueo Nervioso Autónomo/métodos , Bupivacaína/análogos & derivados , Cetoprofeno/análogos & derivados , Nervio Ciático/efectos de los fármacos , Trometamina/farmacología , Anestésicos Locales/administración & dosificación , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Bupivacaína/farmacología , Calor , Inyecciones Subcutáneas , Cetoprofeno/administración & dosificación , Cetoprofeno/farmacología , Levobupivacaína , Dimensión del Dolor , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Trometamina/administración & dosificaciónRESUMEN
Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase and have a major place in the treatment of atherosclerotic disease. Recent studies have shown anti-inflammatory properties of statins. The purpose of this study was to evaluate the anti-inflammatory effect of simvastatin on bleomycin (BLM)-induced pulmonary fibrosis in rats. A total of 31 female Sprague-Dawley rats were divided into four groups: (1) intratracheal (IT) phosphate-buffered saline (PBS) + intraperitoneal (IP) PBS (n=7); (2) IT BLM + IP PBS (n=8); (3) IT BLM + low dose (LD) simvastatin (1 mg/kg daily, n=8); (4) IT BLM + high dose (HD) simvastatin (5 mg/kg daily, n=8). Simvastatin was administered IP for 15 days, beginning 1 day prior to IT BLM. The effect of simvastatin on pulmonary fibrosis was studied by measurements of IL-13, PDGF, IFN-γ, TGF-p1 levels in bronchoalveolar lavage (BAL) fluid and lung tissue hydroxyproline (HPL) content and by histopathological examination (Ashcroft score). BLM caused significant change in BAL fluid cytokine levels and increased both HPL content and histopathological score (p<0.001 for all). While LD simvastatin had no effect on cytokine levels, HD significantly reduced IL-13 (15.12 ±7.08 pg/ml vs. 4.43±2.34 pg/mL; p<0.05) and TGF-ß1 levels (269.25 ±65.42 pg/mL vs. 131.75±32.65 pg/mL; p<0.05). Neither HD nor LD simvastatin attenuated HPL content or Ashcroft score. In conclusion, this study showed that LD simvastatin had no effect on a BLM-induced pulmonary fibrosis model, while the high dose caused partial improvement in profibrotic cytokine levels.
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Antiinflamatorios/uso terapéutico , Fibrosis Pulmonar/tratamiento farmacológico , Simvastatina/uso terapéutico , Animales , Bleomicina , Líquido del Lavado Bronquioalveolar , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1RESUMEN
Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase and have a major place in the treatment of atherosclerotic disease. Recent studies have shown anti-inflammatory properties of statins. The purpose of this study was to evaluate the anti-inflammatory effect of simvastatin on bleomycin (BLM)-induced pulmonary fibrosis in rats. A total of 31 female Sprague-Dawley rats were divided into four groups: (1) intratracheal (IT) phosphate-buffered saline (PBS) + intraperitoneal (IP) PBS (n=7); (2) IT BLM + IP PBS (n=8); (3) IT BLM + low dose (LD) simvastatin (1 mg/kg daily, n=8); (4) IT BLM + high dose (HD) simvastatin (5 mg/kg daily, n=8). Simvastatin was administered IP for 15 days, beginning 1 day prior to IT BLM. The effect of simvastatin on pulmonary fibrosis was studied by measurements of IL-13, PDGF, IFN-γ, TGF-p1 levels in bronchoalveolar lavage (BAL) fluid and lung tissue hydroxyproline (HPL) content and by histopathological examination (Ashcroft score). BLM caused significant change in BAL fluid cytokine levels and increased both HPL content and histopathological score (p<0.001 for all). While LD simvastatin had no effect on cytokine levels, HD significantly reduced IL-13 (15.12 ±7.08 pg/ml vs. 4.43±2.34 pg/mL; p<0.05) and TGF-β1 levels (269.25 ±65.42 pg/mL vs. 131.75±32.65 pg/mL; p<0.05). Neither HD nor LD simvastatin attenuated HPL content or Ashcroft score. In conclusion, this study showed that LD simvastatin had no effect on a BLM-induced pulmonary fibrosis model, while the high dose caused partial improvement in profibrotic cytokine levels.
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Animales , Femenino , Ratas , Antiinflamatorios/uso terapéutico , Fibrosis Pulmonar/tratamiento farmacológico , Simvastatina/uso terapéutico , Bleomicina , Líquido del Lavado Bronquioalveolar , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1RESUMEN
Increased oxidative stress and impaired endothelium-dependent relaxation could underlie many of the vascular complications associated with diabetes. We aimed to investigate the effect of supplementation with grape seed proanthocyanidin extract (GSPE), a natural antioxidant, on vascular responses and oxidative stress in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into three groups: control rats, untreated diabetic rats, and GSPE (100 mg/kg, for 6 weeks)-supplemented diabetic rats. Thoracic aorta rings of the rats were mounted in organ baths, and relaxant responses to acetylcholine (ACh), A23187, and sodium nitroprusside (SNP) were assayed in tissues precontracted with 60 mM KCl. Plasma samples used for the measurement of malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. The endothelium-dependent relaxations in response to ACh and A23187 were impaired, but endothelium-independent relaxation in response to SNP did not change in diabetic rats. Supplementation with GSPE significantly improved the relaxant responses to ACh and A23187. The MDA level was significantly elevated and the plasma SOD activity was decreased in diabetic rats, but supplementation with GSPE attenuated the elevated MDA levels and increased plasma SOD activity. Thus supplementation of GSPE may attenuate oxidative stress through the inhibition of lipid peroxidation and may restore endothelial function and reduce the risk of vascular disease in diabetes.
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Antioxidantes/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Suplementos Dietéticos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Extracto de Semillas de Uva/farmacología , Proantocianidinas/farmacología , Acetilcolina/metabolismo , Animales , Aorta Torácica/efectos de los fármacos , Diabetes Mellitus Experimental/patología , Técnicas In Vitro , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/sangre , Nitroprusiato/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/sangre , Superóxido Dismutasa/metabolismoRESUMEN
INTRODUCTION: Renal ischemia/reperfusion (I/R) which is an important cause of renal dysfunction is inevitable in renal transplantation, surgical revascularization of the renal artery, partial nephrectomy and treatment of suprarenal aortic aneurysms. AIM: The purpose of this study was to investigate the efficacy of α-tocopherol and erdosteine combination in the reduction in injury induced by ROS in a rat model of renal ischemia-reperfusion. MATERIALS AND METHODS: Thirty-six- male Wistar albino rats weighing 200-250 g were utilized for this study. Rats were divided into six groups, and each group was consistent of six rats: (1) sham-operated (control), (2) ischemia group (3) I/R group, (4) I/R/α-tocoferol group (5) I/erdosteine group (6). I/R/α-tocoferol and erdosteine group. Biochemically tissue MDA, XO and SOD activities, light and electron microscopic findings were evaluated. RESULTS: The erdosteine and α-tocoferol significantly reversed the effect of protein oxidation and lipid peroxidation induced by I/R shown by the decreased levels of MDA and XO activities. Both MDA and XO levels were found to be lower in group 6 compared to single agent treatment groups, and this was significantly different. All treatment groups showed increased SOD activity, which accounts for their oxidative properties. The mean Paller score of the combination treatment group (group 6) was lower than all groups except the sham group (3.67 ± 1.2), and this finding was statistically significant (0.05). Our results showed that the antioxidant pretreatment with α-tocopherol and erdosteine combination reduced lipid peroxidation of renal cellular membranes in a model of normothermic renal ischemia-reperfusion in rats. Combination of erdosteine and α-tocopherol has a synergistic effect of protection against oxidative processes. Long-term use of α-tocopherol seems to have a greater effect on the prevention of IR injury. However, further investigations are needed for the clinical applications of our findings.
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Antioxidantes/administración & dosificación , Riñón/irrigación sanguínea , Riñón/patología , Daño por Reperfusión/patología , Tioglicolatos/administración & dosificación , Tiofenos/administración & dosificación , alfa-Tocoferol/administración & dosificación , Animales , Riñón/metabolismo , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/metabolismo , Superóxido Dismutasa/metabolismo , Xantina Oxidasa/metabolismoRESUMEN
The aim of this study was to document the effect of tramadol as an opioid on individual fibers of rat sciatic nerve. To accomplish this objective, compound action potentials (CAPs) were recorded from isolated nerves treated with tramadol from five different concentration levels. Then recorded CAPs and the control group were analyzed by numerical methods namely Conduction Velocity Distribution (CVD) and Fast Fourier Transform (FFT). The results show that the area under CAP and the time derivative of CAP curves decreases, and the excitability of the nerve trunk falls as well (rheobase and chronaxie increases) with increasing tramadol concentration. CVD deduced by model study was divided into subgroups as SLOW (8-26 m/s), MODERATE (26-44 m/s), MEDIUM (44-60 m/s) and FAST (60-78 m/s). The decrement in percentage relative contribution of these conduction velocity groups starts with a concentration of 0.25 mM tramadol, especially in the subgroup named FAST. The power spectrum shifts from higher frequency region to lower frequency region as the tramadol concentration increases. These findings show that fast conducting fibers are more susceptible to tramadol than medium and moderate groups and tramadol possibly acts on channel activity rather than passive properties (such as space and time constant) of nerve fibers.
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Analgésicos Opioides/farmacología , Conducción Nerviosa/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Tramadol/farmacología , Potenciales de Acción/efectos de los fármacos , Animales , Depresión Química , Relación Dosis-Respuesta a Droga , Técnicas In Vitro , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The nervous system, through its important role as a communication network, governs reactions to stimuli, processes information and generates elaborate patterns of signals to control complex behaviors. Although selenium (Se) was shown to have some beneficial effects in pathological conditions, it is still a toxic element with a fairly small therapeutic window. In this study, the direct effects of Se ranging from 10(-8) to 10(-4) M were tested on rat sciatic nerve preparations. The toxicity started at 10(-8) M and the degree of alterations was found to be dose-dependent. In between the measured parameters, total compound action potential area (Astart = 3.70 +/- 0.16 ms x mV and A(-8) M = 3.04 +/- 0.14 ms x mV) and maximum depolarization points (MDstart = 6.70 +/- 0.22 mV and MD(-8) M = 6.04 +/- 0.18 mV) were the first to be affected from 10(-8) M. Latencies and conduction velocity distribution measurements have shown that nerve fibers having intermediate conduction velocities (20-35 m/s) are the first to be affected from this toxicity. Despite the fact that the new claims concluded the positive effects of the administrations, it is evident that the dose of supplementation must be fine-tuned to avoid possible side effects.
Asunto(s)
Potenciales de Acción/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Selenio/toxicidad , Oligoelementos/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Masculino , Fibras Nerviosas/efectos de los fármacos , Fibras Nerviosas/metabolismo , Conducción Nerviosa/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Nervio Ciático/metabolismo , Selenio/administración & dosificación , Oligoelementos/administración & dosificaciónRESUMEN
In the present study, we analysed the effects of leptin on rabbit aorta and the mechanisms underlying these effects. Leptin (10(-12)-10(-9) m) induced concentration-dependent relaxation in intact rabbit aorta rings precontracted with phenylephrine (10(-6) m). Removal of endothelium abolished the effects of leptin. Pretreatment of rings with N(omega)-nitro-l-arginine methyl ester (10(-4) m 20 min) or catalase (1200 U/mL 20 min) significantly reduced the relaxant response to leptin when compared with the control group. The incubation of brefeldin A (3.5 x 10(-5) m 90 min), indomethacin (10(-5) m 20 min), tetraethylammonium (10(-4) m 20 min), and glibenclamide (10(-5) m, 20 min) did not affect the leptin-induced vasodilation. These results suggest that leptin relaxes the rabbit aorta. The relaxation is mediated by endothelium-derived nitric oxide and hydrogen peroxide.
Asunto(s)
Aorta/efectos de los fármacos , Leptina/farmacología , Vasodilatadores/farmacología , Animales , Aorta/fisiología , Factores Biológicos/fisiología , Relación Dosis-Respuesta a Droga , Endotelio Vascular/fisiología , Técnicas In Vitro , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/fisiología , Canales de Potasio/fisiología , Conejos , Vasodilatación/efectos de los fármacosRESUMEN
Gender differences, either with the structural or through with hormones, dictate how the corresponding organ or organ system responses to physiological signals. Current study aims to investigate gender dependent differences in conduction related parameters of rat sciatic nerve. Compound action potentials (CAP) were recorded via suction electrode whereas the conduction velocity distributions (CVD) were performed using the method known as collision technique in the literature. Studied CAP parameters, namely conduction velocities (CV), area of the CAPs and time required to reach the maximum depolarization (TP) have been found significantly different for female and male rats. Detailed analyses have shown that sex dependent differences were more remarkable in the right leg responses of female and male rats. Additionally, CVDs indicate that the number of fibers having CVs between 5-30 m/s is much more in male right sciatic nerve trunk when compared to age matched female rats. The present study, for the first time clearly shows that shift in the contribution of nerve fibers to lower CVs is the main causal of the sex dependent differences seen in rat sciatic nerve fibers.
Asunto(s)
Fibras Nerviosas/fisiología , Conducción Nerviosa/fisiología , Nervio Ciático/fisiología , Factores Sexuales , Potenciales de Acción , Animales , Femenino , Lateralidad Funcional , Técnicas In Vitro , Masculino , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Gender differences are related to the manner in which the heart responds to chronic and acute stress conditions of physiological and pathological nature. Depending on dose, sodium selenite acts as an antioxidant proven to have beneficial effects in several pathological conditions G. Drasch, J. Schopfer, and G. N. Schrauzer, Selenium/cadmium ratios in human prostates: indicators of prostate cancer risk of smokers and nonsmokers, and relevance to the cancer protective effects of selenium, Biol. Trace Element Res. 103(2), 103-107 (2005); R. G. Kasseroller and G. N. Schrauzer, Treatment of secondary lymphedema of the arm with physical decongestive therapy and sodium selenite: a review, Am. J. Ther. 7(4), 273-279 (2000); G. N. Schrauzer, Anticarcinogenic effects of selenium, Cell. Mol. Life Sci. 57(13-14), 1864-1873 (2000); I. S. Palmer and O. E. Olson, Relative toxicities of selenite and selenate in the drinking water of rats, J. Nutr. 104(3), 306-314 (1974). To date, little is known about the gender-dependent direct effects of toxic doses of selenite on electrophysiology of the cardiovascular system H. A. Schroeder and M. Mitchener, Selenium and tellurium in rats: effect on growth, survival and tumors, J. Nutr. 101(11), 1531-1540 (1971); G. N. Schrauzer, The nutritional significance, metabolism and toxicology of selenomethionine, Adv. Food Nutr. Res. 47, 73-112 (2003). In the present study, the effects of in vitro toxic concentrations of sodium selenite ranging from 10-6 M to 10-3 M were tested on both male and female rat heart preparations. The toxic effects seen in an electrocardiogram and left ventricular pressure were dose and sex dependent at most of the tested concentrations. The present study clearly shows that at toxic doses, stress conditions are induced by selenite, resulting in genderdependent modifications of the heart function. This modification is more pronounced in the contraction cascade of female rats. Males, on the other hand, had been much more affected in excitation-related parameters.
Asunto(s)
Corazón/efectos de los fármacos , Miocardio/metabolismo , Selenito de Sodio/farmacología , Animales , Relación Dosis-Respuesta a Droga , Electrocardiografía , Femenino , Masculino , Oxígeno/metabolismo , Perfusión , Presión , Ratas , Factores Sexuales , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
OBJECTIVE: To study the effects of deferoxamine on tissue sodium-potassium adenosine triphosphatase (Na+-K+ ATPase) activity on cerebral ischemia in rabbits. METHODS: We cared for the animals in the Pharmacology Department of the Medical School of Selcuk University in 2004. We used 30, New Zealand, 7-day-old male rabbits in the experiment. We anesthetized all the animals with xylazine hydrochloric acid and ketamine. We divided the rabbits equally into 3 groups. In group 1 (n=10) (sham group), we observed baseline levels, and did not apply ischemia. In group 2 (n=10) (untreated group) we produced cerebral ischemia by clamping the bilateral common carotid arteries for 60 minutes, and in group 3 (n=10), we administered deferoxamine (DFO) 50 mg/kg intravenously immediately after opening the clamps. RESULTS: The Na+-K+ATPase activity increased after DFO treatment (p=0.045). CONCLUSION: We conclude that Na+-K+ATPase activity in cortical brain tissue was higher in DFO-treated rabbits compared with untreated animals after ischemia.