RESUMEN
OBJECTIVE: The aim of this study was to investigate the dose-dependent anti-inflammatory effect of the Hydrogen sulfidedonor sodiumhydrosulphide on acute necrotizing pancreatitis in rats. MATERIAL AND METHODS: A total of 42 male Sprague-Dawley rats were divided into 4 groups: sham+saline (group 1), sham+NaHS (group 2), acute necrotizing pancreatitis+saline (group 3), and acute necrotizing pancreatitis+NaHS (group 4). Acute pancreatitis was induced in rats in groups 3 and 4 with the infusion of glycodeoxycholic acidinto the biliopancreatic canal and infusion of cerulein parenterally. In group 4, 10 mg/kg NaHS was administered intraperitoneally after cerulein infusion. Tests for liver and kidney function, interleukin-6, lactate dehydrogenase in bronchoalveolar lavage, and malonyaldehyde and myeloperoxidase activities in pancreas and lung tissue were performed, and histopathologic examination of pancreas was conducted. RESULTS: In groups 3, a significant increase in amylase, alanine aminotransferase, urea, interleukine-6, lungmalondialdehyde and myeloperoxidase activities, pancreas myeloperoxidase activity, edema, and necrosis in pancreas tissue and a significant decrease in serum calcium levels were detected (p<0.05). In group 4, addition of NaHS resulted in a significant decrease in lactate dehydrogenase level in bronchoalveolar lavage, amount of urea, lung myeloperoxidase activity, and pancreatic edema (p<0.05). CONCLUSION: Although not in pancreatic necrosis, hydrogen sulphide has an anti-inflammatory effect especially in the inflammatory process in lung and edema in pancreasin acute necrotizing pancreatitis at particular doses. With further studies evaluating the anti-inflammatory effects of hydrogen sulphide, we believe it can be used in the treatment of edematous acute pancreatitis and the related complications in lungs.
RESUMEN
BACKGROUND: This study investigated the effect of caffeic acid phenethyl ester (CAPE) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. CAPE, an active component of honeybee propolis, has previously been determined to have antioxidant, anti-inflammatory, antiviral, and anticancer activities. MATERIALS AND METHODS: Forty-eight rats were divided into four groups of 12. Group 1 animals received intraductal saline and intravenous saline infusion treatment. Group 2 was given intraductal saline and intraperitoneal CAPE infusion treatment. ANP was induced in the animals in group 3 (ANP with saline infusion), and group 4 had induced ANP plus CAPE infusion treatment (ANP with CAPE infusion). Sampling was performed 48 h after treatment. RESULTS: ANP induction significantly increased mortality rate, pancreatic necrosis, and bacterial infection in pancreatic and extrapancreatic organs. ANP also increased levels of amylase and alanine aminotransferase (ALT) in serum, increased levels of urea and lactate dehydrogenase in bronchoalveolar lavage fluid (BAL LDH), increased the activities of myeloperoxidase (MPO) and malondialdehyde (MDA) in pancreas and lung tissue, and decreased the serum calcium levels. The use of CAPE did not significantly reduce the mortality rate but significantly reduced the ALT and BAL LDH levels, the activities of MPO and MDA in the pancreas, the activity of MDA in the lungs, and pancreatic damage. The administration of CAPE did not reduce the bacterial infection. CONCLUSIONS: These results indicate that CAPE had beneficial effects on the course of ANP in rats and suggest that CAPE shows promise as a treatment for ANP.
Asunto(s)
Antioxidantes/uso terapéutico , Ácidos Cafeicos/uso terapéutico , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Alcohol Feniletílico/análogos & derivados , Alanina Transaminasa/sangre , Animales , Antioxidantes/farmacología , Traslocación Bacteriana/efectos de los fármacos , Líquido del Lavado Bronquioalveolar , Ácidos Cafeicos/farmacología , Detergentes , Modelos Animales de Enfermedad , Ácido Glicodesoxicólico , L-Lactato Deshidrogenasa/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Masculino , Malondialdehído/metabolismo , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Páncreas/microbiología , Pancreatitis Aguda Necrotizante/inducido químicamente , Pancreatitis Aguda Necrotizante/metabolismo , Peroxidasa/metabolismo , Alcohol Feniletílico/farmacología , Alcohol Feniletílico/uso terapéutico , Ratas , Ratas Sprague-DawleyRESUMEN
The aim of this study was to investigate the influence of enalaprilat on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in a significant increase in the mortality rate, pancreatic necrosis, serum activity of amylase, alanine aminotransferase (ALT), and interleukin-6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, serum concentration of urea, and tissue activity of myeloperoxidase (MPO) and maondialdehyde (MDA) in the pancreas and lung, and a significant decrease in concentrations of calcium, blood pressure, urine output and p0(2). The use of enalaprilat inhibited the changes in urine output, blood pressure, serum concentration of urea, p0(2), and tissue activity of MPO and MDA in the pancreas and lungs. It reduced the mortality and pancreatic damage. Enalaprilat demonstrated a beneficial effect on the course of ANP in rats; therefore, it may be used in the treatment of acute pancreatitis.
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Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enalaprilato/farmacología , Pulmón/efectos de los fármacos , Páncreas/efectos de los fármacos , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Alanina Transaminasa/sangre , Amilasas/sangre , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Presión Sanguínea/efectos de los fármacos , Líquido del Lavado Bronquioalveolar/química , Calcio/metabolismo , Ceruletida , Modelos Animales de Enfermedad , Enalaprilato/uso terapéutico , Ácido Glicodesoxicólico , Interleucina-6/sangre , L-Lactato Deshidrogenasa/metabolismo , Pulmón/enzimología , Pulmón/patología , Masculino , Malondialdehído/metabolismo , Oxígeno/sangre , Páncreas/enzimología , Páncreas/patología , Pancreatitis Aguda Necrotizante/inducido químicamente , Pancreatitis Aguda Necrotizante/metabolismo , Pancreatitis Aguda Necrotizante/patología , Pancreatitis Aguda Necrotizante/fisiopatología , Presión Parcial , Peroxidasa/metabolismo , Ratas , Ratas Sprague-Dawley , Urea/sangre , Micción/efectos de los fármacosRESUMEN
AIM: The modulation of cytokine release, which affects adhesion of leucocytes to endothelial cells, and proliferation of peripheral blood mononuclear cells with antihypertensive drugs was explored. METHOD: In the present study, mononuclear cells were incubated with losartan and amlodipine at concentrations of 10(-6), 10(-5) and 10(-4) mol/L for 6 h. Transforming growth factor (TGF)-beta and tumour necrosis factor (TNF)-alpha levels were measured. Proliferation of mononuclear cells were assessed at the same concentrations of amlodipine and losartan with the methylthiazoletetrazolium (MTT) test. RESULTS: Amlodipine was found to induce TGF-beta synthesis from mononuclear cells with increasing concentrations, while it was found to inhibit TNF-alpha secretion with increasing concentrations. In contrast, losartan was found to induce TGF-beta and TNF-alpha secretion with increasing concentrations. CONCLUSION: Anti-atherosclerotic effects of amlodipine and losartan might be through increased secretion of TGF-beta from mononuclear cells. Different results at different concentrations might be due to the pharmocokinetic differences of these drugs.
Asunto(s)
Amlodipino/farmacología , Antihipertensivos/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Losartán/farmacología , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/inmunología , Células Cultivadas , Humanos , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/metabolismoRESUMEN
OBJECTIVES: Behçet's disease is a multisystem disorder characterized by a chronic inflammation including acute attacks and remission periods. Decreased enzyme activity of the antioxidant system and increased levels of free radicals may have important roles in the damage of tissues observed in the disease period. In addition, the atherogenic tendency of serum lipid, lipoproteins, lipid peroxidation levels and endothelial dysfunction accompany the above mentioned findings. As a consequence of these events, different degrees of low density lipoprotein (LDL) oxidation occur in vivo, and then autoantibodies against oxidized-LDL(AuAb-oxLDL) are produced. DESIGN AND METHODS: Lipids, lipoproteins, lipid hydroperoxide, AuAb-oxLDL, total antioxidant status (TAS), serum-soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor 1 (PAI-1) levels in serum, the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) in erythrocytes and plasma, were determined in 25 patients with Behçet's disease and in 25 healthy volunteers. Also, susceptibility to copper-induced in vitro oxidation of LDL by using lag time, a measure of resistance to oxidation, oxidation rate and extent of oxidation, a measure of diene production in both groups, was studied. RESULTS: It was observed that lipid hydroperoxide and AuAb-oxLDL levels in patients with Behçet's disease were significantly higher, but erythrocyte SOD, CAT, plasma GSH-Px activities, and TAS were significantly lower than those in healthy subjects. Susceptibility of LDL to oxidation in the patients was found to be increased. Total cholesterol, LDL-C and apo B levels and acute phase reactants were significantly higher, but HDL-C and apo AI levels were significantly lower, in patients when compared to healthy subjects. The levels of AuAb-oxLDL in patients were found to correlate with TAS, total cholesterol, LDL-C, lipid hydroperoxide and erythrocyte SOD activities (r = -0.62, p < 0.01; r = 0.64, p < 0.01; r = 0.55, p < 0.01; r = 0.81, p < 0.01; r = -0.63, p < 0.01, respectively). In addition, lipid hydroperoxide levels were found to correlate with total cholesterol, LDL-C and erythrocyte SOD activities (r = 0.45, p < 0.05; r = 0.45, p < 0.05; r = -0.46, p < 0.05, respectively). PAI-1 and sICAM-1 were found to be increased in the patients and correlated with AuAb-oxLDL and lipid hydroperoxide levels (r = 0.56, p < 0.01; r = 0.67, p < 0.01 and r = 0.59, p < 0.01; r = 0.61, p < 0.01, respectively). CONCLUSIONS: It was concluded that the observed increase of lipid, lipoproteins, lipid hydroperoxide, susceptibility of LDL to oxidation, autoantibodies against ox-LDL levels and decrease of antioxidant enzyme activities and total antioxidant status and increased secretion of endothelial derivated peptides including sICAM and PAI-1, and their interactions may indicate that there is a tendency to atherothrombotic events in patients with Behçet's disease.
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Antioxidantes/metabolismo , Autoanticuerpos/inmunología , Síndrome de Behçet/inmunología , Síndrome de Behçet/metabolismo , Endotelio/fisiopatología , Peróxidos Lipídicos/sangre , Lípidos/sangre , Lipoproteínas LDL/inmunología , Adulto , Síndrome de Behçet/sangre , Síndrome de Behçet/fisiopatología , Catalasa/metabolismo , Femenino , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Humanos , Lipoproteínas LDL/sangre , Lipoproteínas LDL/metabolismo , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Superóxido Dismutasa/metabolismoRESUMEN
Endothelin-1 (ET-1) is a vasoconstrictor peptide derived from endothelium. Many authors have shown that ischemic stroke is associated with elevated plasma ET-1 levels. Also, the present findings related to plasma ET-1 levels with clinical status, size of the infarction, location of the infarction, and prognosis of the cerebral infarction were contradictory. In this study, plasma ET-1 levels in 30 patients with cerebral infarction within 72 hours after the onset of focal neurologic deficit and at their seventh day postinfarction were measured by a microplate enzyme immunoassay. Thirty sex- and age-matched healthy subjects were accepted as a control group. The mean plasma ET-1 concentrations in patients on admission, in patients at day 7, and in control subjects were 1.93 +/- 1.79, 1.03 +/- 1.02, and 0.65 +/- 0.32 fmol/mL, respectively. The mean plasma ET-1 level of patients on admission was found to be significantly higher than in patients at day 7 and in control subjects (p < 0.05). No significant difference in ET-1 levels was observed between the patients at day 7 and control subjects. Furthermore, there was no correlation between plasma ET-1 concentration and size of infarction, location of infarction, degree of clinical neurologic deficit, or prognosis of cerebral infarction. It was concluded that plasma ET-1 levels shortly after ischemic stroke were increased, which may be associated with the acute-phase reaction of cerebral infarction and may have deleterious effects on development of neuronal injury.
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Infarto Cerebral/sangre , Infarto Cerebral/complicaciones , Endotelina-1/sangre , Enfermedades del Sistema Nervioso/sangre , Enfermedades del Sistema Nervioso/etiología , Adulto , Anciano , Anciano de 80 o más Años , Infarto Cerebral/diagnóstico por imagen , Femenino , Humanos , Técnicas para Inmunoenzimas , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/diagnóstico por imagen , Neutrófilos , Pronóstico , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To investigate the effects of the tyrosine kinase inhibitor tyrphostin AG 556 on the course of acute necrotising pancreatitis in rats. DESIGN: Laboratory study. SETTING: Medical school, Turkey. ANIMALS: 72 Sprague Dawley rats, 12 in the sham operated (control) group and 20 in each of the three others. MAIN OUTCOME MEASURES: Cardiorespiratory measurements, mortality, effect on the activities of various enzymes in serum and tissue of pancreas and lung, and the histological picture. RESULTS: The four study groups were sham + Ringer's lactate, acute necrotising pancreatitis with Ringer's lactate, tryphostin AG 556, and dimethylsulfoxide (DMSO). There were 12 animals in the first group and 20 in each of the other groups. The induction of pancreatitis increased mortality from 0/12 in the control to 6/20 (30%), 7/20 (35%), 8/20 (40%) in the three experimental groups, respectively. Heart rate, packed cell volume (PCV), serum activities of amylase and alanine aspartate transferase, tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, serum concentrations of urea and calcium, volume of ascites, degree of pancreatic damage, blood pressure, and urine production did no differ between the pancreatitis groups. CONCLUSIONS: Treatment with the tyrphostin kinase inhibitor did not improve the course of acute pancreatitis or reduce the extent of acinar cell injury and is therefore unlikely to be of benefit in patients with pancreatitis.