Effects of sulfasalazine on lipid peroxidation and histologic liver damage in a rat model of obstructive jaundice and obstructive jaundice with lipopolysaccharide-induced sepsis

AbstractBackground: Sulfasalazine, an inhibitor of cyclooxygenase, 5-lipoxygenase, and nuclear factor κB (NF-κB), has been found to alleviate oxidative damage, proinflammatory cytokine production, bile-duct proliferation, neutrophil infiltration, and fibrosis. Therefore, it may have a potential effect in attenuating lipid peroxidation and histologic liver damage in patients with biliary obstruction and biliary obstruction with sepsis.Objective: The aim of this study was to investigate the effect of sulfasalazine on lipid peroxidation and histologic liver damage due to obstructive jaundice (OJ) and to OJ with lipopolysaccharide (LPS)-induced sepsis in an experimental model.Methods: Male Wistar rats, weighing 150 to 220 g, were randomized into 6 groups: OJ; OJ + LPS; OJ + sulfasalazine; OJ + sulfasalazine + LPS (sulfasalazine administered before sepsis); OJ + LPS + sulfasalazine (sulfasalazine administered after sepsis); and sham. Liver malondialdehyde (MDA) and myeloperoxidase (MPO) activities were assessed to monitor lipid peroxidation and neutrophil infiltration in liver tissue. Histologic liver damage was evaluated with hematoxylin-eosin stained slides. Liver tissue NF-κB and caspase-3 expression were studied immunohistopathologically to evaluate lipid peroxidation, liver damage, and hepatocyte apoptosis.Results: Forty-eight rats were evenly randomized into 6 groups of 8. MDA (P = 0.001), MPO (P = 0.001), NF-κB (P = 0.003), caspase-3 expression (P = 0.002), and liver injury scores (P = 0.002) increased significantly in the OJ group compared with the sham group. Compared with the OJ group, MDA (P = 0.030) and MPO levels (P = 0.001), and liver injury scores (P = 0.033) were decreased significantly in the OJ + sulfasalazine group. In the OJ + sulfasalazine + LPS and OJ + LPS + sulfasalazine groups, MDA (P = 0.008 and P = 0.023, respectively) and MPO (both, P = 0.001) were significantly decreased; however, liver NF-κB, caspase-3 expression, and liver injury scores were not significantly different compared with the OJ + LPS group. There was no significant difference between the OJ + LPS + sulfasalazine and OJ + sulfasalazine + LPS groups in regard to all end points when comparing the effects of sulfasalazine administered before or after sepsis.Conclusions: Sulfasalazine was associated with decreased neutrophil accumulation and lipid peroxidation in these rats with OJ. Administration of sulfasalazine before or after LPS-induced sepsis was associated with a reduction in lipid peroxidation and neutrophil accumulation; however, it did not attenuate histologic liver damage. There was no difference between the findings when sulfasalazine was administered before or after sepsis in OJ

Effect of ornithine on the ileal histology, nitric oxide production and lipid peroxidation in LPS-induced endotoxemia.

Effect of ornithine which is known to inhibit L-arginine uptake via cationic amino acid transport system has been tested, and compared to aminoguanidine, an iNOS inhibitor in lypopolysaccharide (LPS)-induced endotoxemia in rats. Serum nitrite/nitrate and malondialdehyde (MDA) level have been measured, and ileal histology has also been examined. Endotoxin increased serum nitrite/nitrate and MDA levels from 15.7+/- 2.4 micromol/ml and 2.1 +/-0.2 nmol/ml to 23.1 +/- 1.0 micromol/ml and 5.2+/- 0.3 nmol/ml (both P&#60;0.05), respectively. In addition, LPS caused ileal degeneration. L-ornithine (500 mg/kg) did not improve septic manifestations, i.e., serum nitrite/nitrate and MDA levels did not differ from those in endotoxemia. Neither does it have an improving action on ileal histology. However, higher dose of L-ornithine (2,500 mg/kg) lowered the increased level of nitrite/nitrate and MDA by LPS. Moreover, it restored ileal histology from grade 3 (median) to 0 (median) (P&#60;0.05). On the other hand, aminoguanidine (100 mg/kg) normalized serum nitrite/nitrate and MDA levels but not ileal histology in endotoxemic rats. In conclusion, high dose of L-ornithine could improve endotoxemic parameters in LPS-treated rats.</p

Elevated Blood Lead Concentrations in Essential Tremor: A Case–Control Study in Mersin, Turkey

Essential tremor (ET) is one of the most common neurologic disorders. Aside from underlying susceptibility genes, recent studies have also begun to focus on environmental toxic factors. Yet there remains a paucity of information on such factors, making studies of environmental factors important. A recent study in New York City found blood lead concentrations to be elevated in ET cases compared with matched controls. Chronic exposure to lead produces cerebellar damage, and this could predispose individuals to develop ET

Comparison and evaluation of experimental mediastinitis models: precolonized foreign body implants and bacterial suspension inoculation seems promising

BACKGROUND: Post-sternotomy mediastinitis (PSM) is a devastating surgical complication affecting 1–3% of patients that undergo cardiac surgery. Staphylococcus aureus is one of the most commonly encountered bacterial pathogen cultured from mediastinal samples obtained from patients with PSM. A component of the membrane of the gram positive bacteria, lipoteichoic acid, stimulates the blood monocytes and macrophages to secrete cytokines, radicals and nitrogen species leading to oxido-inflammatory damage. This seems to be responsible for the high mortality rate in PSM. For the evaluation of the pathogenesis of infection or for the investigation of alternative treatment models in infection, no standard model of mediastinitis seems to be available. In this study, we evaluated four mediastinitis models in rats. METHODS: The rats were divided into four groups to form different infection models. Group A: A suspension of 1 × 10(7 )colony-forming units Staphylococcus aureus in 0,5 mL was inoculated from the right second intercostal space into the mediastinum. Group B: A hole was created in the right second intercostal space and a piece of stainless-steel implant with a length of 0.5 cm was inserted into the mediastinum and a suspension of 1 × 10(7 )cfu bacteria in 0,5 mL was administered via the tail vein. Group C: Precolonized stainless-steel implant was inserted into the mediastinum. Group D: Precolonized stainless-steel implant was inserted into the mediastinum and the bacteria suspension was also injected into the mediastinum. On the 10(th )day, rats were sacrificed and the extension of infection in the mediastenae was evaluated by quantitative cultures. Myeloperoxidase activity (MPO) and malondialdehyde (MDA) levels were determined in the sera to evaluate the neutrophil activation and assess the inflammatory oxidation. RESULTS: The degree of infection in group C and D were 83.3% and 100% respectively (P < 0.001). MDA levels were significantly higher in these two groups than the others (P < 0.001). CONCLUSION: Infected implants and high bacterial concentration administration were the two important components that played a significant role in the outcome of a successful infection in mediastinum in a rat model

Vitamin D Deficiency And Its Association With Inflammatory Markers, Lipid Profile And Regulatory T-Cells In Pediatric Sickle Cell Disease Patients

We investigated vitamin D deficiency in pediatric sickle cell disease patients and its association with selected bone, lipid and inflammatory parameters. The study included 64 patients (33 SS and 31 SB) and 21 carriers (AS). Blood was obtained to assess levels of vitamin D, WBC, CRP, Ca, P, ALP, PTH, triglyceride, total cholesterol, LDL, VLDL, HDL, IL-2, IL-12, TNF-alpha, IL-4, IL-6, IL-10 and regulatory T cells. The patients were grouped according to their genotype (SS, SB) and vitamin D status (low or normal). Carriers were also grouped as low or normal vitamin D. Laboratory findings were similar between low and normal Vit D groups in SS, SB and AS genotypes except a lower IL-12 in SB-low vitamin D compared SB-normal vitamin D group. Acute chest syndrome was more frequent in SS-low Vit D (63%) compared to SS-normal Vit D (25%), SB-low Vit D (21%) and SB-normal Vit D (33%) (P = 0.045). Both SS and SB with low vitamin D had higher VLDL (P = 0.006 and P = 0.022), TNF-alpha (P = 0.001) and regulatory T cells (P = 0.000) compared to AS-low vitamin D. Both SS and SB with normal vitamin D had higher levels of regulatory T cells (P = 0.000) compared to AS-normal vitamin D. Vit D was not a modifier of selected inflammation, bone and lipid parameters in sickle cell disease. Acute chest syndrome was comparably more frequent in SS-low vitamin D. Increase of regulatory T cells in the patients was a result of chronic inflammation in sickle cell disease.Wo

Investigation into miRNA profile in patient groups with and without ST elevation

Because acute myocardial infarction (AMI) may occur suddenly and cannot be predicted, it is critical to identify early diagnosis markers. In recent years, in addition to the developing diagnostic methods, other markers that may be related to the diagnosis of AMI are miRNA molecules. The specificity of miRNAs involved in the pathogenesis of atherosclerosis and regulation of cardiac functions has been shown. The present study aimed to investigate the changes in miRNA expression levels in MI patients with ST-elevation (STEMI) and without ST elevation (NSTEMI)

Reactive nitrogen intermediates in plasmodium vivax malaria in Cukurova region, Turkey

WOS: 000202990001122

Functional association of interleukin-18 gene-607 C/A promoter polymorphisms with endometriosis

WOS: 000285411600076PubMed: 20797704This study evaluated for the first time the relationship between interleukin-18 (IL-18) C607A genotypes and endometriosis in 135 women with endometriosis and 84 controls. In the study population, IL-18 -607*A homozygote and A allele were positively correlated with the risk of developing endometriosis or the stage of endometriosis. (Fertil Steril (R) 2011; 95:298-300. (c) 2011 by American Society for Reproductive Medicine.

Liver tissue inducible nitric oxide synthase (iNOS) expression and lipid peroxidation in experimental hepatic ischemia reperfusion injury stimulated with lipopolysaccharide: The role of aminoguanidine

Background. Hepatic ischemia-reperfusion (HIR) is a severe condition that is seen after hepatic arterial injury and in hepatic grafts in living donor transplantation. HIR not only causes liver injury by lipid peroxidation, but also stimulates systemic and portal endotoxemia. Also, lipopolysaccharide (LPS) induces hepatic injury mediated by inducible nitric oxide synthase (iNOS). There is little knowledge on the role of specific iNOS inhibitors in prevention of HIR injury followed by LPS administration. The aim of this study on a LPS induced HIR model was to investigate the effect of aminoguanidine (AG) administration on hepatic tissue iNOS expression and lipid peroxidation when given before or after LPS