RESUMEN
Melatonin is a powerful endogenous antioxidant hormone. Its healing effects on energy balance and neuronal damage associated with oxidative metabolism disorders have been reported in pathologic conditions. We aimed to determinate the utility of melatonin on neuronal damage, synaptic transmission, and energy balance in the brain tissue of rats with sepsis induced with LPS. Rats was divided into four groups such as control, LPS (20 mg/kg i.p.), melatonin (10 mg/kg i.p. × 3), and LPS + Melatonin (LPS + Mel). After 6 h from the first injection, rats were decapitated, and also tissue and serum samples were taken. Lipid peroxidation and neuron-specific enolase (NSE) levels were determined from the serum in all group. High energy compounds, creatine, and creatine phosphate are measured by HPLC methods from the homogenized tissue. Counts of living neurons are marked with NeuN (neuronal nuclei), degenerated neurons are marked with S100-ß and synaptic vesicles transmission is analyzed with synaptophysin antibodies immunoreactivities. One-way ANOVA and post hoc Tukey tests were used to statistical analysis. In LPS group, AMP, ATP, creatine, and creatine phosphate levels were significantly decreased (p < 0.05), and also ADP levels were significantly increased compared with the other groups (p < 0.01). Living neurons counts were significantly decreased in LPS (p < 0.01), melatonin, and LPS + Melatonin (p < 0.05) groups compared with control. Degenerated neurons counts were increased in LPS group compared with control (p < 0.01) and also decreased in both of melatonin and LPS + Melatonin groups (p < 0.01). Synaptophysin immunoreactivity was decreased in LPS group compared with the other groups (p < 0.05). We observed that melatonin administration prevents neuronal damage, regulates energy metabolism, and protects synaptic vesicle proteins from sepsis-induced reduction.
RESUMEN
Trace elements are cofactors in various enzymes in the antioxidant defense and cell homeostasis required in the tissue during inflammation. In acute kidney injury induced by lipopolysaccharide (LPS), renal cells are affected by cytotoxicity. Renal evacuation and gastrointestinal absorption rates are important in regulating plasma levels of trace elements. Simvastatin is a widely used anti-lipidemic drug with known anti-inflammatory effects. This study aimed to examine the effect of simvastatin on trace elements and electrolyte levels in kidney tissue in rats with LPS-induced sepsis. Adult male Wistar albino rats were divided into four groups: control, LPS (20 mg/kg, i.p., single dose), simvastatin (20 mg/kg, o.p., 5 days), and LPS + Simvastatin (LPS + Sim). Sodium, potassium, calcium, magnesium, selenium, zinc, copper, and histological structural changes were examined in kidney tissue samples 4 h after LPS execution. The inductively coupled plasma optical emission spectroscopy technique (ICP-OES) was used to determine the tissue trace element levels. In rats with sepsis-induced LPS, selenium, calcium, sodium, and magnesium levels significantly decreased while copper, potassium, and zinc levels significantly increased compared to other experimental groups. In sepsis treated with the simvastatin (LPS + Simvastatin) group, trace elements and electrolyte levels are like the control groups, apart from selenium levels. Selenium levels were significantly decreased in the LPS + Simvastatin group compared to the controls. As a result of examining the kidney tissues under a light microscope, simvastatin improved tissue damage caused by LPS-induced acute kidney injury. LPS-induced renal injury and simvastatin caused significant changes in the oxidant/antioxidant system. In septic rats, simvastatin was shown to balance some trace element levels, and it may improve damage in the kidney tissue.
RESUMEN
We aimed to investigate the effects of melatonin administered before and during endotoxemia on the lung tissue of rats, cytokine, YKL-40, matrix metalloproteinase (MMP) and inhibitor levels, oxidative stress parameters, and energy balance. Sepsis was induced with lipopolysaccharide (LPS), the cell wall molecule of gram negative bacteria. Rats were divided into four groups, Control, LPS (Escherichia coli O127:B8, 20 mg/kg), melatonin (10 mg/kg), and melatonin+LPS (M+LPS). After injections, lung tissues samples were taken for experimental analyses. YKL-40, thiobarbituric acid reactive substances (TBARS), glutathione reductase (GR), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) enzymes levels were measured, high-energy components were analyzed; tumor necrosis factor-alpha (TNF-α), MMP-2, YKL-40, MMP-9, myeloperoxidase (MPO), tissue inhibitors of matrix metalloproteinase (TIMP)-1, and interleukin (IL)-10 immunoreactivities were investigated. In LPS group, YKL-40, creatine phosphate (both, p < 0.05), SOD, GR, adenosine mono-phophate (AMP), adenosine tri-phosphate (ATP) (for all, p < 0.01) were significantly decreased, while TBARS and adenosine di-phosphate (ADP) levels were increased (p < 0.01, p < 0.05; respectively) compared to other groups. MMP-2 and -9, TIMP-1, TNF-α, IL-10, and MPO immunoreactivity were investigated in LPS group. On the contrary, in M+LPS group, MMP-9, TIMP-1 immunoreactivities were not found and IL-10 and MMP-2 immunoreactivities were found with little involvement. In M+LPS group, YKL-40, GR, AMP, ATP, creatine phosphate (for all, p < 0.05), and SOD (p < 0.01) levels were significantly increased and TBARS levels were decreased (p < 0.05). In our study, we suggest that melatonin exerts a protective and curative effect by reducing the matrix metalloproteinase levels responsible for tissue damage balance, stimulating the release of antioxidant enzymes, regulating cytokines and energy balance during endotoxemia.
Asunto(s)
Endotoxemia , Melatonina , Adenosina , Adenosina Monofosfato/uso terapéutico , Adenosina Trifosfato , Animales , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Proteína 1 Similar a Quitinasa-3 , Endotoxemia/tratamiento farmacológico , Endotoxemia/patología , Glutatión Reductasa , Interleucina-10 , Lipopolisacáridos , Pulmón/patología , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Metaloproteinasas de la Matriz , Melatonina/farmacología , Melatonina/uso terapéutico , Fosfatos , Fosfocreatina/uso terapéutico , Ratas , Superóxido Dismutasa , Sustancias Reactivas al Ácido Tiobarbitúrico , Inhibidor Tisular de Metaloproteinasa-1 , Factor de Necrosis Tumoral alfa/uso terapéuticoRESUMEN
There are a number of studies investigating anti-inflammatory effects of simvastatin in patients with sepsis and animal models. There are a few studies which investigated effect of simvastatin on elements in sepsis. In the present study, the impact of pretreatment with simvastatin on element levels was evaluated in liver during endotoxemia. Rats were divided into control, LPS, simvastatin, and simvastatin + LPS. The histopathologic examination of the liver was performed using hematoxylin and eosin. Selenium, zinc, iron, manganese, magnesium, and copper were analyzed using inductively coupled plasma - optical emission spectroscopy. In the LPS, the hepatocyte cell structure was damaged. In the simvastatin + LPS, hepatocyte, and sinusoidal cord damage were partially smaller than LPS. Levels of selenium, and copper significantly decreased in both of LPS and simvastatin + LPS. In the LPS group, iron was found to increase. In the simvastatin + LPS, zinc was increased. Simvastatin partially smaller liver damage by increasing zinc levels during endotoxemia.
Asunto(s)
Endotoxemia/tratamiento farmacológico , Lipopolisacáridos/farmacología , Hígado/efectos de los fármacos , Simvastatina/farmacología , Oligoelementos/análisis , Animales , Antiinflamatorios/farmacología , Cobre/análisis , Hepatocitos/efectos de los fármacos , Hierro/análisis , Magnesio/análisis , Masculino , Manganeso/análisis , Ratas , Ratas Wistar , Selenio/análisis , Zinc/análisisRESUMEN
Galectins constitute of a soluble mammalian ß-galactoside binding lectin family, which play homeostatic roles in the regulation of the cell cycle, and apoptosis, in addition to their inflammatory conditions. Galectin-3 has an important role in the regulation of various inflammatory conditions including endotoxemia, and airway inflammation. Statins, the key precursor inhibitors of 3-hydroxyl-3-methyl coenzyme A (HMG-CoA) reductase, may prevent the progression of inflammation in sepsis after prior statin treatment. Endotoxemia leads to the formation of oxidative stress parameters in proteins, carbohydrates, and DNA. In the present study, we aimed to show the effects of simvastatin on Galectin-3, and glutathione reductase (GR), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and thiobarbituric acid reactive substances (TBARS) levels in lung tissue of rats which were treated with lipopolysaccharides (LPS) during the early phase of sepsis. Rats were divided into four groups as the control, LPS (20 mg/kg), simvastatin (20 mg/kg), and simvastatin+LPS group. Galectin-3 expression in formalin-fixed paraffin-embedded lung tissue sections was demonstrated by using the immunohistochemistry methods. There were reduced densities, and the decreased number of Galectin-3 immunoreactivities in the simvastatin+LPS group compared with the LPS group in the pneumocytes, and in the bronchial epithelium of lung tissue. In the LPS group, GR, GSH-Px, and SOD were found lower than the levels in simvastatin-treated LPS group (P<0.05, P<0.01, P<0.01 respectively) in the lung tissue. However, TBARS decreased in the simvastatin+LPS group compared with the levels in LPS group (P<0.001). Simvastatin attenuates LPS-induced oxidative acute lung inflammation, oxidative stress, and suppresses LPS-induced Galectin-3 expression in the lung tissue.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Endotoxemia/tratamiento farmacológico , Galectina 3/genética , Estrés Oxidativo/efectos de los fármacos , Neumonía/tratamiento farmacológico , Simvastatina/farmacología , Animales , Antioxidantes/metabolismo , Endotoxemia/inducido químicamente , Endotoxemia/genética , Endotoxemia/patología , Galectina 3/antagonistas & inhibidores , Galectina 3/metabolismo , Regulación de la Expresión Génica , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/genética , Glutatión Reductasa/metabolismo , Inyecciones Intraperitoneales , Lipopolisacáridos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Masculino , Neumonía/inducido químicamente , Neumonía/genética , Neumonía/patología , Ratas , Ratas Wistar , Transducción de Señal , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
We aimed to investigate the effects of prior treatment of simvastatin on mitochondrial enzyme, ghrelin, and hypoxia-inducible factor 1 α (HIF-1 α) on hepatic tissue in rats treated with Lipopolysaccharides (LPS) during the early phase of sepsis. Rats were divided into four groups: control, LPS (20 mg/kg, i.p.), Simvastatin (20 mg/kg, p.o.), and LPS + Simvastatin group. We measured citrate synthase, complex I, II, I-III, II-III enzymes activities, serum and tissue levels of TNF-α, IL-10 using ELISA. Liver sections underwent histopathologic examination and TNF-α, IL-10, HIF-1α and ghrelin immunoreactivity were examined using immunohistochemistry methods. There were no differences in all groups for mitochondrial enzyme activities. In terms of both ELISA and immunohistochemistry findings; the levels of serum and tissue TNF-α and IL-10 were higher in the experimental groups than controls (P < 0.05). In the LPS group, the hepatocyte cell membrane and sinusoid structure were damaged. In the Simvastatin +LPS group, hepatocytes and sinusoidal cord structure were partially improved. For HIF-1α, in all experimental groups immunoreactivity was increased (P < 0.05). In the Simvastatin group, Ghrelin levels were increased in comparison with the other groups (P < 0.01). Ghrelin levels were greatly decreased in LPS (P < 0.05). We observed that the degree of hepatocellular degeneration was partially reduced depending on the dosage and duration of prior simvastatin treatment with LPS, probably due to alterations of Ghrelin and HIF-1α levels.
RESUMEN
We investigated the effects of the early phase of sepsis and prior treatment of Simvastatin on muscle structure and mitochondrial enzymes treated with lipopolysaccharide (LPS) in rats. We divided rats into control, LPS, simvastatin, simvastatin + LPS groups. Mitochondrial citrate synthase, complex I, II, I + III, II + III, cytochrome c oxidase (COX) activities were measured. Muscle tissue was stained using modified Gomori trichrome (MGT), succinic dehydrogenase (SDH) and cytochrome oxidase (COX). In all treated groups, complex I and citrate synthase activities were higher than in the controls. In the control and LPS groups, COX activity was increased when compared with simvastatins'. Complex II, II-III activities were higher in the LPS group than in the control group. Complex I-III activities were higher in the Simvastatin and Simvastatin + LPS groups than in the control and LPS groups (P < 0.05). Myopathic changes with LPS group were observed in MGT stained sections. Our findings showed improvements in the alterations of enzyme activities and muscle myofibrils after treating rats with LPS that had received a prior dose of simvastatin.