Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bioartificial kidney (BAK) consists of a conventional hemofiltration cartridge in series with a renal tubule assist device (RAD) containing 10(9) porcine renal proximal tubule cells. BAK replaces filtration, transport, and metabolic and endocrinologic activities of a kidney. Previous work in an acutely uremic dog model demonstrated that BAK ameliorated endotoxin (lipopolysaccharide [LPS])-induced hypotension and altered plasma cytokine levels. To further assess the role of BAK in sepsis in acute renal failure, dogs were nephrectomized and 48 h later administered intraperitoneally with 30 x 10(10) bacteria/kg of E. coli. One hour after bacterial administration, animals were placed in a continuous venovenous hemofiltration circuit with either a sham RAD without cells (n = 6) or a RAD with cells (n = 6). BP, cardiac output, heart rate, pulmonary capillary wedge pressure, and systemic vascular resistance were measured throughout the study. All animals tested were in renal failure, with blood urea nitrogen and serum creatinine concentrations greater than 60 and 6 mg/dl, respectively. RAD treatment maintained significantly better cardiovascular performance, as determined by arterial BP (P < 0.05) and cardiac output (P < 0.02), for longer periods than sham RAD therapy. Consistently, all sham RAD-treated animals, except one, expired within 2 to 9 h after bacterial administration, whereas all RAD-treated animals survived more than 10 h. Plasma levels of TNF-alpha, IL-10, and C-reactive protein (CRP) were measured during cell RAD and sham RAD treatment. IL-10 levels were significantly higher (P < 0.01) during the entire treatment interval in the RAD animals compared with sham controls. These data demonstrated in a pilot large animal experiment that the BAK with RAD altered plasma cytokine levels in acutely uremic animals with septic shock. This change was associated with improved cardiovascular performance and increased survival time. These results demonstrate that the addition of cell therapy to hemofiltration in an acutely uremic animal model with septic shock ameliorates cardiovascular dysfunction, alters systemic cytokine balance, and improves survival time.
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PMID:Bioartificial kidney ameliorates gram-negative bacteria-induced septic shock in uremic animals. 1253 47

The effect of Wen-Pi-Tang extract on renal injury induced by peroxynitrite (ONOO-) production was investigated using rats subjected to intravenous lipopolysaccharide (LPS) injection and then renal ischemia followed by reperfusion. The plasma level of 3-nitrotyrosine, a marker of cytotoxic ONOO formation in vivo, was enhanced markedly in control rats subjected to LPS plus ischemia-reperfusion, but was significantly reduced by the oral administration of Wen-Pi-Tang extract, at doses of 62.5 and 125 mg/kg body weight/day, for 30 days prior to LPS plus ischemia-reperfusion. The activities of inducible nitric oxide synthase (iNOS) and xanthine oxidase (XOD) in renal tissue of control and Wen-Pi-Tang extract-treated rats did not change significantly, while those of the antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase, were significantly increased by the administration of Wen-Pi-Tang extract, indicating that Wen-Pi-Tang improved the defense system by scavenging free radicals, not by directly inhibiting nitric oxide and superoxide production by iNOS and XOD. In addition, the levels of the hydroxylated products, m- and p-tyrosine, declined, whereas that of phenylalanine increased, after oral administration of Wen-Pi-Tang extract. Furthermore, the elevated plasma urea nitrogen and creatinine levels resulting from LPS plus ischemia-reperfusion process were significantly reduced by Wen-Pi-Tang extract, implying amelioration of renal impairment. The present study indicates that Wen-Pi-Tang extract contributes to the regulation of ONOO- formation and plays a beneficial role against ONOO(-) -induced oxidative injury and renal dysfunction in vivo.
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PMID:Prevention of peroxynitrite-induced renal injury through modulation of peroxynitrite production by the Chinese prescription Wen-Pi-Tang. 1260 16

Despite the fact that septic shock is characterized by a decrease in systemic vascular resistance, the main cause of death is due to multiple organ failure. The organ dysfunction is usually attributed to cell death caused by overproduction of free radicals derived from inflammation. In the host infected by endotoxin (lipopolysaccharide, LPS), the expression and release of proinflammatory tumor necrosis factor-alpha (TNF-alpha) rapidly increases, and the formation of free radicals (e.g., superoxide anion [O2*-] and nitric oxide [NO*] in the present study) are inevitably overproduced. In this study, we present evidence that overall treatment of LPS rats with terbutaline, a beta2-adrenoceptor agonist, attenuates the delayed hypotension and ameliorates the tachycardia. Overproduction of TNF-alpha and NO* (produced by inducible NO synthase [iNOS] examined by Western blot analysis in the lung and the liver) is inhibited by treatment of LPS rats with terbutaline. In addition, treatment of endotoxemic rats with terbutaline also reduces the O2*- levels in the lung and the liver. Terbutaline also improves the liver (assessed by aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin/globulin) and kidney (assessed by creatinine and uric acid) dysfunction induced by endotoxin. These findings suggest that the amelioration of circulatory failure and organs injury by terbutaline is associated with its suppression in TNF-alpha, O2*- and NO (via iNOS) production in animals with endotoxic shock.
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PMID:Inhibition by terbutaline of nitric oxide and superoxide anion levels of endotoxin-induced organs injury in the anesthetized rat. 1263 May 30

The effects of a monoclonal antibody (mAb) to tumor necrosis factor-alpha (TNF-alpha) were examined in a rabbit model of endotoxic shock. Intravenous administration of lipopolysaccharide (100 microg/kg/hr) for 6 hours (n = 11) increased TNF-alpha levels. Fibrinogen was partially consumed, and fibrin deposits were seen in kidney and lungs at 24 hours. Mortality at 24 hours was 64%. Levels of interleukin-8 (aka CXCL-8) were notably increased. Mean arterial pressure (MAP) and leukocyte counts decreased, whereas creatinine levels were enhanced. The anti-TNF-alpha mAb (20 mg/kg i.v. bolus + 5 mg/kg/h i.v. for the first 90 minutes) (n = 10) efficiently inhibited the TNF-activity. Rabbits exhibited lower CXCL-8 levels; MAP improved, the decrease in leukocyte counts was partially prevented and creatinine levels were lower, but fibrinogen, fibrin deposits in kidneys and lungs and mortality, 55%, were similar to the LPS group. Rabbits that did not survive exhibited lower fibrinogen levels, more fibrin in kidneys and lungs and higher CXCL-8 and creatinine levels than survivors, while there were no differences in TNF-alpha, MAP and leukocytes. Thus, the inhibition of TNF-alpha, although beneficial through lowering CXCL-8 levels, is not enough to improve the outcome, which could be partly due to the inability to prevent the fibrin deposits formation in kidneys and lungs.
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PMID:Tumor necrosis factor-alpha inhibition reduces CXCL-8 levels but fails to prevent fibrin generation and does not improve outcome in a rabbit model of endotoxic shock. 1267 71

Endotoxemia causes an enhanced production of reactive oxygen radicals, which contribute to multiple organ dysfunction. When rats were given intravenous lipopolysaccharide and tested 6 h later we found that the activities of catalase and glutathione peroxidase (GSH-Px) in kidney, were acutely suppressed while in serum the levels of nitric oxide (NO), lipid peroxidation, urea nitrogen and creatinine were significantly increased, indicating the excessive production of reactive oxygen radicals and the presence of renal injury. Pretreatment of rats with Acanthopanax Radix extract administered orally for 30 days reduced the NO and lipid peroxidation levels, increased the activities of catalase and GSH-Px, and attenuated the renal dysfunction. These results suggested that scavenging of reactive oxygen radicals is part of the mechanism by which Acanthopanax Radix extract works as an effective agent in preventing multiple organ dysfunction.
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PMID:Protective effects of Acanthopanax Radix extract against endotoxemia induced by lipopolysaccharide. 1272 39

The protective effect of (-)-epicatechin 3-O-galate (ECg) against peroxynitrite (ONOO-)-mediated damage was examined using an animal model and a cell culture system. In rats subjected to lipopolysaccharide (LPS) administration plus ischemia-reperfusion, the plasma 3-nitrotyrosine level an indicator of ONOO- production in vivo, was elevated, whereas it declined significantly and dose-dependently after the oral administration of ECg at doses of 10 and 20 micromoles/kg body weight/day for 20 days prior to the process. Moreover, oral administration of ECg significantly enhanced the activities of the antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase, and the antioxidant glutathione, showing enhancement of the biological defense system against the damage induced by ONOO-. In addition, the significant increase in the renal mitochondrial thiobarbituric acid-reactive substance level of LPS and ischemic-reperfused control rats was attenuated in rats given ECg. Furthermore, the elevations in the plasma urea nitrogen and creatinine (Cr) levels and the urinary methylguanidine/Cr ratio induced by the procedure were attenuated markedly after oral administration of ECg, implying amelioration of renal impairment. The addition of ECg (25 or 125 microM) prior to 3-morpholinosydnonimine (SIN-1, 800 microM) exposure reduced ONOO- formation and increased the viability of cultured renal epithelial (LLC-PK1) cells in a dose-dependent manner. In particular, ECg inhibited ONOO(-)-mediated apoptotic cell death, which was confirmed by decreases in the DNA fragmentation rate and the presence of apoptotic morphological changes, i.e. small nuclei and nuclear fragmentation. Furthermore, adding ECg before SIN-1 treatment regulated the cell cycle by enhancing G2/M phase arrest. This study provides evidence that ECg has protective activity against the renal damage induced by excessive ONOO- in cellular and in vivo systems.
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PMID:Protective activity of (-)-epicatechin 3-O-gallate against peroxynitrite-mediated renal damage. 1279 78

Lipopolysaccharide is strongly associated with septic shock, leading to multiple organ failure. It can activate monocytes and macrophages to release proinflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and nitric oxide (NO). The present experiments were designed to induce endotoxin shock by an intravenous injection of Klebsiella pneumoniae lipopolysaccharide (LPS, 10 mg/kg) in conscious rats. Arterial pressure and heart rate (HR) were continuously monitored for 48 h after LPS administration. N-Acetylcysteine was used to study its effects on organ damage. Biochemical substances were measured to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-alpha, IL-1 beta, methyl guanidine (MG), and nitrites/nitrates. LPS caused significant increases in blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, IL-1 beta, MG levels, and HR, as well as a decrease in mean arterial pressure and an elevation of nitrites/nitrates. N-Acetylcysteine suppressed the release of TNF-alpha, IL-1 beta, and MG, but enhanced NO production. These actions ameliorate LPS-induced organ damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound in sepsis prevention and treatment.
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PMID:N-acetylcysteine ameliorates lipopolysaccharide-induced organ damage in conscious rats. 1496 65

Several studies have implicated a role of peptidoglycan (PepG) as a pathogenicity factor in sepsis and organ injury, in part by initiating the release of inflammatory mediators. We wanted to elucidate the structural requirements of PepG to trigger inflammatory responses and organ injury. Injection of native PepG into anesthetized rats caused moderate but significant increases in the levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and bilirubin (markers of hepatic injury and/or dysfunction) and creatinine and urea (markers of renal dysfunction) in serum, whereas PepG pretreated with muramidase to digest the glycan backbone failed to do this. In an ex vivo model of human blood, PepG containing different amino acids induced similar levels of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, and IL-10, as determined by plasma analyses (enzyme-linked immunosorbent assay). Hydrolysis of the Staphylococcus aureus cross-bridge with lysostaphin resulted in moderately reduced release of TNF-alpha, IL-6, IL-8, and IL-10, whereas muramidase digestion nearly abolished the ability to induce cytokine release and IL-6 mRNA accumulation in CD14(+) monocytes compared to intact PepG. However, additional experiments showed that muramidase-treated PepG synergized with lipopolysaccharide to induce TNF-alpha and IL-10 release in whole blood, despite its lack of inflammatory activity when administered alone. Based on these studies, we hypothesize that the structural integrity of the glycan chain of the PepG molecule is very important for the pathogenic effects of PepG. The amino acid composition of PepG, however, does not seem to be essential for the inflammatory properties of the molecule.
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PMID:Organ injury and cytokine release caused by peptidoglycan are dependent on the structural integrity of the glycan chain. 1497 33

This study was carried out to elucidate whether the protective activity of (-)-epicatechin 3-O-gallate (ECg) against excessive peroxynitrite (ONOO(-)) production, is distinct from the activity of several well-known free radical inhibitors, the ONOO(-) inhibitors ebselen and uric acid, the superoxide anion (O(2)(-)) scavenger copper zinc superoxide dismutase (CuZnSOD) and the selective inducible nitric oxide synthase inhibitor L-N(6)-(1-iminoethyl)lysine hydrochloride (L-NIL). To generate ONOO(-), male Wistar rats (n = 6/group) were subjected to ischaemia-reperfusion process together with lipopolysaccharide (LPS) injection. Although ECg did not scavenge the ONOO(-) precursors nitric oxide (NO) and O(2)(-), it reduced the 3-nitrotyrosine level, a property similar to that of uric acid, but distinct from L-NIL. In addition, the elevation in myeloperoxidase activity was reversed by the administration of ECg, uric acid and SOD, but not by that of L-NIL. Furthermore, ECg was the more potent scavenger of the ONOO(-) decomposition product, the hydroxyl radical (*OH), than any other free radical inhibitor tested. The LPS plus ischaemia-reperfusion process resulted in renal dysfunction, estimated by measuring the parameters of renal function--serum urea nitrogen and creatinine levels. However, administration of ECg ameliorated renal dysfunction more than that of the other free radical inhibitors. Moreover, ECg reduced the excessive uric acid level, while the others did not, suggesting a property of ECg distinct from the others. Furthermore, proteinuria, which was demonstrated by the low- and high-molecular weight (LMW and HMW) protein bands of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis pattern, caused by LPS plus ischaemia-reperfusion, was attenuated by administration of ECg and L-NIL, after which the HMW band intensities decreased and LMW protein bands were absent. This study indicates that, in an in-vivo model of ONOO(-) generation, ECg, L-NIL and uric acid exert stronger protective activity against ONOO(-)-induced oxidative damage than SOD and ebselen, and that the mechanism whereby ECg protects against ONOO(-) is distinct from that of L-NIL or uric acid.
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PMID:(-)-Epicatechin 3-O-gallate ameliorates the damages related to peroxynitrite production by mechanisms distinct from those of other free radical inhibitors. 1500 82

We aimed to test the protective effect of dopexamine on renal function and systemic haemodynamics in rats with induced sepsis. Female Sprague-Dawley rats were randomized into three equal groups: group 1 (control, received 3% creatinine throughout the experiment); group 2 (sepsis, received 3% creatinine and Escherichia coli lipopolysaccharide [LPS] endotoxin [8 mg/kg per h]); and group 3 (sepsis plus dopexamine, received 3% creatinine, E. coli LPS and dopexamine [1 microgram/kg per min]). Time-adjusted heart rate, systolic, diastolic and mean arterial pressures, urine volume and glomerular filtration rate (from creatinine clearance) were recorded. After bacterial infusion heart rate increased and mean arterial pressure decreased; the fall in mean arterial pressure was less pronounced with dopexamine (group 3) than without (group 2). Dopexamine also induced significant and moderate increases in urine volume and heart rate, respectively. We concluded that dopexamine has some positive inotropic-chronotropic effects and induces favourable responses in renal function.
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PMID:Effects of dopexamine on rat cardiorenal functions during lipopolysaccharide-induced experimental sepsis. 1508 13


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