RESUMEN
Background: The incidence of metabolic syndrome is increasing worldwide and this is mainly attributed to high carbohydrate intake, especially of fructose, and sedentary lifestyles. Nitric oxide (NO), which is synthesized by nitric oxide synthase (NOS) enzymes, is a crucial molecule for endothelial and renal health. Asymmetric dimethylarginine (ADMA) is the most potent inhibitor of NOS and it is degraded by dimethylarginine dimethylaminohydrolase (DDAH). The aim of this study was to investigate the effects of melatonin on renal NO-ADMA metabolism using a metabolic syndrome model achieved by fructose administration. Methods: Thirty-two rats were randomly divided into four groups (n = 8): (1) control group, (2) fructose group, (3) melatonin group, and (4) fructose + melatonin group. Fructose (20%) was given in drinking water. Melatonin [20 mg/(kg·day)] was administered in 0.1% ethanol solution. After 8 weeks, kidney tissues were collected to measure tissue levels of nitrite/nitrate (NOx), ADMA, arginine, symmetric dimethylarginine, DDAH activity, and endothelial NOS (eNOS) and inducible NOS (iNOS) protein levels. Results: Fructose led to low arginine/ADMA ratios (AARs) (P < 0.008). Tissue NOx levels of the fructose + melatonin group were significantly higher than those of the fructose group (P < 0.008). ADMA and arginine were significantly higher in the fructose + melatonin group than the control group (P < 0.008). The DDAH activity of the fructose and fructose + melatonin groups was significantly higher than that of the control group (P < 0.008). eNOS protein levels showed no difference and iNOS protein was not detected in any of the groups. Conclusions: A diminished AAR indicates the toxicity of fructose in the kidneys. Melatonin has beneficial effects on the NO-ADMA pathway as it restores NOx levels and increases DDAH activity, possibly as a result of a compensatory mechanism to metabolize increased ADMA.
Asunto(s)
Melatonina , Síndrome Metabólico , Animales , Arginina/análogos & derivados , Fructosa , Riñón , Melatonina/farmacología , Síndrome Metabólico/inducido químicamente , Síndrome Metabólico/tratamiento farmacológico , Óxido Nítrico , Óxido Nítrico Sintasa , RatasRESUMEN
The aims of the present study were to develop a colon-specific gel formulation of melatonin with sodium alginate and to evaluate its in vitro characteristics and intracolonic performance on oxidative stress parameters, such as nitric oxide (NOx), malondialdehyde (MDA) and glutathione (GSH) levels in rats with acetic acid-induced colitis. The melatonin-alginate gel formulations were prepared and their physico-pharmaceutical properties were determined. Formulation M5, which contained 3% of sodium alginate and 20% polyethylene glycol, was used for in vivo studies. The in vivo studies were conducted in rats with acetic acid-induced colitis. NOx, MDA and GSH levels were determined and histological investigations were performed. It was found that formulation M5 was the most suitable formulation for the colon-specific melatonin gel, in terms of pH, viscosity, drug release and mucoadhesion properties. The MDA levels in the tissues of Group 2 (treated with an intracolonic gel formulation without melatonin) were found to be significantly higher than in Group 1 (the untreated group). NOx levels decreased with the intracolonic and systemic melatonin treatment in the colitis-induced rats. Neither intracolonic nor intra-peritoneal (IP) melatonin treatment affected GSH levels. The epitelization of the colon tissues in groups administered with intracolonic melatonin, IP melatonin, and the intracolonic gel formulation without melatonin was much better than that found in the untreated group. It was concluded that melatonin participated in various defense mechanisms against the colonic inflammatory process, and that the dose, route and formulation type were the most important parameters in the effectiveness of melatonin.
Asunto(s)
Ácido Acético/química , Colitis/tratamiento farmacológico , Geles/administración & dosificación , Geles/química , Glutatión/metabolismo , Malondialdehído/administración & dosificación , Malondialdehído/química , Melatonina/administración & dosificación , Melatonina/farmacología , Óxido Nítrico/química , Animales , Composición de Medicamentos , Glutatión/química , Melatonina/química , RatasRESUMEN
AIM: The purpose of this study was to evaluate the effects of hyperbaric oxygen (HBO) and HBO preconditioning (pre-HBO) on experimental wound healing and tensile strength in the colonic anastomosis of rats. MATERIALS AND METHODS: A total of 21 Sprague-Dawley rats were divided into three random groups of equal numbers: sham operation, pre-HBO, and HBO. Sham group was given standard left colon resection and end-to-end anastomosis; pre-HBO group received HBO as one dose + colonic resection + anastomosis; HBO group was given colonic resection + anastomosis + HBO. HBO was administrated at 24-hr intervals and relaparatomy was performed on the fifth day. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNF-α), and hydroxy (OH)-proline levels and anastomotic burst pressure were evaluated. RESULTS: Burst pressure and OH-proline levels markedly increased in the HBO group compared with the sham and pre-HBO groups. When compared with the sham group, MDA and MPO levels were significantly decreased in the HBO and pre-HBO groups. In contrast to these findings, SOD and GSH-Px levels were increased in the HBO group as compared with the sham and pre-HBO groups. TNF-α, IL-6, and IL-10 values were detected at low levels in the HBO group as compared with other groups. CONCLUSIONS: HBO administration accelerated wound healing and strengthened the anastomotic tissue. In the light of these results, the HBO administration has beneficial effects and contributed to wound healing in colonic anastomosis. But, as expected, pre-HBO did not alter the results significantly.
Asunto(s)
Colon/cirugía , Oxigenoterapia Hiperbárica , Cuidados Preoperatorios , Cicatrización de Heridas , Anastomosis Quirúrgica , Animales , Biomarcadores/sangre , Colágeno/análisis , Citocinas/sangre , Hidroxiprolina/análisis , Masculino , Estrés Oxidativo , Oxígeno/sangre , Presión Parcial , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Dehiscencia de la Herida Operatoria/prevención & control , Resistencia a la Tracción , Cicatrización de Heridas/efectos de los fármacosRESUMEN
CONTEXT: Melatonin, a pineal hormone and a potent antioxidant, has important roles in metabolic regulation. OBJECTIVE: This study investigated serum asymmetric dimethylarginine (ADMA), homocysteine (Hcy), nitric oxide (NO) levels, known to be reliable markers of cardiovascular diseases, and determined possible protective effects of melatonin in fructose-fed rats. MATERIALS AND METHODS: Sprague-Dawley rats were divided into four groups: control, fructose, melatonin, and fructose plus melatonin. Metabolic syndrome was induced in rats by 20% (w/v) fructose solution in tap water, and melatonin was administered at the dose of 20 mg/kg bw per day by oral gavage. After 8 weeks, serum lipids, glucose, insulin, ADMA, Hcy, and NOx (the stable end products of NO) levels were quantified. RESULTS: Fructose administration caused a statistically significant increase in systolic blood pressure (SBP), serum insulin, triglycerides, and very low-density lipoprotein (VLDL)-cholesterol levels compared with the control group and the metabolic syndrome model was successfully demonstrated. In comparison with the control group, fructose caused a significant increase in serum ADMA, Hcy, and NOx levels. Melatonin counteracted the changes in SBP, serum ADMA, and Hcy levels found in rats both alone and administered with fructose. DISCUSSION AND CONCLUSION: These results show that high fructose consumption leads to elevated SBP, atherogenic lipid profile, increased serum ADMA, and Hcy levels and melatonin treatment has beneficial effects on these biochemical parameters in rats. Melatonin might be beneficial for the prevention and/or treatment of the cardiovascular complications of metabolic syndrome not only by reducing the well-known risk factors of the disease but also by diminishing blood ADMA and Hcy levels.
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Arginina/análogos & derivados , Fructosa/toxicidad , Homocisteína/sangre , Melatonina/uso terapéutico , Síndrome Metabólico/sangre , Óxido Nítrico/sangre , Animales , Arginina/sangre , Biomarcadores/sangre , Masculino , Melatonina/farmacología , Síndrome Metabólico/inducido químicamente , Síndrome Metabólico/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley , Resultado del TratamientoRESUMEN
Taurine is a sulfur-containing ß-amino acid that is found in milimolar concentrations in most mammalian tissues and plasma. It was shown to have cytoprotective effects in many in vitro and in vivo studies and these actions are often attributed to an antioxidant mechanism. In this study, we aimed to investigate the effect of acute taurine administration on endotoxin-induced oxidative and nitrosative stress in brain. Fourty adult male guinea pigs were divided into four groups: control, taurine, endotoxemia, and endotoxemia + taurine. Taurine (300 mg/kg), lipopolysaccharide (LPS, 4 mg/kg), or taurine plus LPS was administered intraperitoneally. After 6 h of incubation, when highest blood levels of taurine and endotoxin were attained, the animals were killed and brain tissue samples were collected. 3-Nitrotyrosine (3-NT), 8-hydroxydeoxyguanosine (8-OHdG) and taurine levels were measured using high-performance liquid chromatography methods. LPS administration significantly increased 3-NT, 8-OHdG levels, and dramatically reduced taurine concentrations in brain tissue compared to control group. The groups in which taurine was administered alone or with LPS, contradiction to well-known antioxidant effect, taurine caused elevated concentrations of 3-NT and 8-OHdG compared to both control and endotoxemia groups. In conclusion, endotoxemia leads to tyrosine nitration and DNA base modification that can be assessed by 3-NT and 8-OHdG, respectively. Taurine did not exhibit any antioxidant effect; moreover, it may contribute to neuronal damage at this dose. Thus, we can suggest that lower dose of taurine administration may be benefial for neuronal protection or adversely taurine administration may have toxic effect at all doses.
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Encéfalo/metabolismo , Desoxiguanosina/análogos & derivados , Endotoxemia/metabolismo , Taurina/farmacología , Tirosina/análogos & derivados , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Antioxidantes/farmacología , Encéfalo/efectos de los fármacos , Desoxiguanosina/metabolismo , Cobayas , Lipopolisacáridos/inmunología , Masculino , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Taurina/uso terapéutico , Tirosina/metabolismoRESUMEN
INTRODUCTION: Denervation decreases skeletal muscle's energy needs and alters its metabolism and circulation. Our study was designed in two stages to investigate the effects of surgical and chemical denervation on the ischaemia/reperfusion injury of skeletal muscle. Degenerative histological analysis, apoptosis scoring and tissue levels of malonyl-di-aldehyde (MDA) and nitric oxide end products (NOx) were studied to understand the extent of ischaemia/reperfusion injury of skeletal muscles. MATERIALS-METHODS: In the first stage, the effect of surgical denervation was investigated in four groups each containing six rats. The right biceps femoris muscle was used as the experimental muscle flap model. In the control group, only the ischaemia/reperfusion cycle was applied. Ischaemia was created by a tourniquet strictly wrapping the right lower extremity for 4 h. After ischaemia, the tourniquet was cut, and the extremity was reperfused for another 4 h. In the experimental groups, surgical denervation was applied 1 day, 7 days and 30 days before the ischaemia/reperfusion cycle. On the second stage, the effect of chemical denervation with botulinum toxin type-A (BoNT-A) was investigated in three groups, each containing six rats. In the experimental groups, BoNT-A was applied 1 day, 7 days and 30 days before the ischaemia/reperfusion cycle. RESULTS: The control group had the worst scores in all experiment parameters. Degenerative histology and apoptosis scores were significantly better in groups to which BoNT-A and SD were applied 1 or 7 days before the ischaemia/reperfusion cycle. Regarding tissue levels of MDA and NOx, the experiment groups had significantly better scores comparing to the control group. CONCLUSION: Both surgical and chemical denervation applied before muscle transfer increased muscle ischaemia tolerance. With similar experimental outcomes, denervation with BoNT-A can be preferred to surgical denervation because of its abundant clinical availability and it can be applied without any secondary surgery.
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Músculo Esquelético/trasplante , Daño por Reperfusión/terapia , Colgajos Quirúrgicos , Simpatectomía Química/métodos , Animales , Apoptosis , Modelos Animales de Enfermedad , Estudios de Seguimiento , Miembro Posterior/irrigación sanguínea , Miembro Posterior/inervación , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/efectos de los fármacos , Ratas , Ratas Wistar , Daño por Reperfusión/patología , Resultado del TratamientoRESUMEN
Taurine (2-aminoethanesulfonic acid) is a free sulfur-containing ß-amino acid which has antioxidant, antiinflammatory and detoxificant properties. In the present study, the role of endotoxemia on peroxynitrite formation via 3-nitrotyrosine (3-NT) detection, and the possible antioxidant effect of taurine in lipopolysaccharide (LPS)-treated guinea pigs were aimed. 40 adult male guinea pigs were divided into four groups; control, endotoxemia, taurine and taurine+endotoxemia. Animals were administered taurine (300 mg/kg), LPS (4 mg/kg) or taurine plus LPS intraperitoneally. After 6 h of incubation, when highest blood levels of taurine and endotoxin were attained, the animals were sacrificed and spleen samples were collected. The amounts of 3-nitrotyrosine and taurine were measured by HPLC, and reactive nitrogen oxide species (NOx) which are stable end products of nitric oxide was measured spectrophotometrically in spleen tissues. LPS administration significantly decreased the concentration of taurine whilst increased levels of 3-NT and NOx compared with control group. It was determined that taurine treatment decreased the levels of 3-nitrotyrosine and NOx in taurine+endotoxemia group. The group in which taurine was administered alone, contradiction to well-known antioxidant effect, taurine caused elevated concentration of 3-NT and NOx. This data suggest that taurine protects spleen against oxidative damage in endotoxemic conditions. However, the effect of taurine is different when it is administered alone. In conclusion, taurine may act as an antioxidant during endotoxemia, and as a prooxidant in healthy subjects at this dose.
Asunto(s)
Endotoxemia/metabolismo , Óxido Nítrico/metabolismo , Bazo/efectos de los fármacos , Taurina/uso terapéutico , Tirosina/análogos & derivados , Animales , Antioxidantes/uso terapéutico , Endotoxemia/tratamiento farmacológico , Cobayas , Lipopolisacáridos , Masculino , Bazo/metabolismo , Taurina/administración & dosificación , Tirosina/metabolismoRESUMEN
It has been proposed that taurine may function as an oxidant in a dose-dependent manner in vivo and in vitro. The present study was carried out to investigate the relationship between taurine concentration and 3-nitrotyrosine level, a stable marker of peroxynitrite action, in hepatocytes of guinea pig in endotoxemia before and after taurine administration. The levels of taurine and 3-nitrotyrosine were measured by HPLC method. In the present study, taurine was low concentration in hepatocytes exposed to endotoxemia. In taurine plus endotoxin treated animals, HPLC analysis showed higher taurine level compared with animals only supplemented with taurine. But 3-nitrotyrosine levels were same in both taurine alone and taurine plus endotoxin groups. In conclusion, taurine is able to prevent the damaging effect of peroxynitrite, at concentration measured in hepatocytes, in our experimental conditions.