Therapeutic effects of simvastatin on Galectin-3 and oxidative stress parameters in endotoxemic lung tissue

Galectins constitute of a soluble mammalian beta-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

Effect of low-energy shockwave therapy on angiogenic factors in the penile tissue of diabetic rats

Objective: The aim of this study is to investigate the effect of low-energy shock wave therapy (LESWT) on angiogenesis factors at penile tissue in a diabetic rat model

The effects of amrinone and glucagon on verapamil-induced cardiovascular toxicity in anaesthetized rats

The goal of this study was to compare the effects of glucagon and amrinone on mean arterial pressure (MAP) and heart rate, when used alone and in combination, in an anaesthetized rat model of verapamil toxicity. Rats were anaesthetized and the carotid artery was cannulated for MAP and heart rate measurements. Jugular and femoral veins were cannulated for drug administration. After verapamil infusion (15 mg/kg/h), control animals were given normal saline solution and the other groups received amrinone (0.1 or 0.2 mg/kg/min), glucagon (0.3 mg/kg bolus followed by 0.1 or 0.2 mg/kg/min infusion), glucagon plus amrinone (0.1 mg/kg/min and 0.1 mg/kg/min respectively) or glucagon plus amrinone (0.2 mg/kg/min and 0.1 mg/kg/min respectively). Glucagon (0.2 mg/kg/min) significantly increased MAP when compared to the control group (P < 0.01). The combination of glucagon and amrinone did not produce a synergistic effect for the recovery of MAP. Furthermore, this combination masked the positive effects of glucagon (0.2 mg/kg/min) on MAP.Glucagon (0.2 mg/kg/min) increased the heart rates compared with those of the control group (P < 0.05). Additionally, amrinone (0.1 mg/kg/min) plus glucagon (0.1 mg/kg/min) increased the heart rates (P < 0.05). Finally, glucagon dose dependently recovered MAP. While amrinone depressed MAP in combination with glucagon, it did not alter the positive chronotropic effect of high dose glucagon

Sağlıklı Çocuklarda Gelişen Varisella Enfeksiyonu Sırasında Bağışıklık Sisteminde Geçici Baskılanma

Objective: Varicella is a common childhood infection and has a number of complications in the unvaccinated population. Perforin, found in natural killer cells, is important for the killing of virally infected cells. For this reason, the am of this study was to determine natural killer cell count and activity, perforin expression, and Fas and soluble Fas ligand (sFas-L) levels in immunocompetent children with varicella infection and define any possible relations between the levels and varicella complications. Material and Methods: Forty children were analyzed at diagnosis and on the 15th day of varicella infection. There was a significant difference in hemoglobin levels and leukocyte and platelet counts between days 0 and 15. Results: Thirteen (32%) patients were found to be lymphopenic, Natural killer cell count and activity were significantly higher on day 15 when compared to values at diagnosis. The Fas-mediated apoptotic pathway was found to be active in acute varicella infection because Fas and sFas-L levels at diagnosis were higher than values on day 15. Conclusion: These findings suggest that the Fas and Fas-L apoptotic pathway is active during the acute phase of the viral infection and that it becomes inactive by day 15, paralleling the hematologic recovery. (Turk J Hematol 2009; 26: 12-6)Wo

Effect of simvastatin on mitochondrial enzyme activities, ghrelin, hypoxia-inducible factor 1α in hepatic tissue during early phase of sepsis

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

Role of simvastatin in endotoxemia-induced muscle injury

We aimed to investigate the role of prior treatment of simvastatin on cytokine response, energy levels, and apoptotic molecules on muscle tissue in rats treated with lipopolysaccharide (LPS) during the early phase of sepsis. Male Wistar albino rats (200-250 g) were divided into four groups: control, endotoxemia (20 mg/kg, i.p.), simvastatin (20 mg/kg, p.o.), and simvastatin + endotoxemia. Four hours after the beginning of the experiments, 8 rats from each group were sacrificied and gastrocnemius muscle tissue was dissected to examine for histologic changes using hematoxylin-eosin staining. The gene expressions of TNF-alpha, IL-10 and Bcl-2, Bax, and Caspase-3 mRNA levels were analyzed using real-time polymerase chain reaction. Creatine, creatine phosphate, adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels were investigated in muscle tissue using high performance liquid chromatography. ATP values were found low in the endotoxemia group and increased in the Simvastatin + endotoxemia group compared with the endotoxemia group (P < 0.05). Caspase-3, Bax, and TNF-alpha levels were significantly higher in the endotoxemia group than in the other groups (P < 0.01). In the simvastatin + endotoxemia group, Bcl-2 and TNF-alpha (P < 0.05), and IL-10 (P < 0.01) levels were higher than other groups. Muscle sections of the LPS group showed inflammation and atrophic areas. Tissue injury was reduced in the simvastatin + endotoxemia groups sections. Sepsis caused an increase of pro-inflammatory cytokine TNF-alpha and pro-apoptotic proteins; caspase-3 and Bax in muscle tissue may also have caused tissue damage. Pretreatment of simvastatin reduced muscle tissue damage by increasing levels of the anti-inflammatory cytokine IL-10 and the anti-apoptotic protein Bcl-2