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 effects of betaine or taurine on hepatotoxicity induced by lipopolysaccharide (LPS) were examined in adult male SD rats. Rats were provided with drinking water containing either 1% betaine or taurine for 2 weeks prior to challenge with LPS (5 mg/kg, iv). Supplementation with betaine or taurine protected the animals from induction of LPS hepatotoxicity as measured by changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities and total bilirubin levels in serum, and hepatic glutathione contents. LPS challenge increased serum TNF-alpha and nitrate/nitrite in rats, which were reduced by betaine or taurine intake. Taurine depletion induced by supply of drinking water containing 3% beta-alanine for 7 days did not enhance the LPS-induced hepatic damage or the decrease in hepatic glutathione level. The results indicate that intake of betaine or taurine attenuates the LPS-induced hepatotoxicity resulting from activation of Kupffer cells.
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PMID:Attenuation of bacterial lipopolysaccharide-induced hepatotoxicity by betaine or taurine in rats. 1189 13

There has been a widespread impression that tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) mediate the toxicity of high doses of lipopolysaccharide (LPS, endotoxin) and are key factors in septic shock. However, the clinical efficacy of treatment with antagonists of TNF-alpha and IL-1beta is still controversial, suggesting that mediators other than TNF-alpha and IL-1beta might contribute causally to endotoxin-induced death. Recent studies implicated high mobility group-1 (HMG-1) protein as a late mediator of endotoxin lethality in mice. However, the role of HMG-1 in mediating multiple organ damage-associating trauma has not been studied. This study was designed to investigate changes in HMG-1 gene expression in vital organs, and its potential role in mediating multiple organ damage following major burns. Wistar rats were subjected to a 35 percent full-thickness thermal injury, and randomly divided into three groups as follows: normal controls (n = 7), thermal injury (n = 24), and recombinant bactericidal/permeability-increasing protein (rBPI21) treatment (n = 12). Tissue samples from liver and lungs were collected to measure tissue endotoxin levels and HMG-1 mRNA expression. In addition, blood samples were obtained for measurement of organ function parameters. Our data demonstrated a significant increase in HMG-1 gene expression in tissues at 24 h postburn, which remained markedly elevated up to 72 h after thermal injury (P< 0.05-0.01). Treatment with rBPI21 could significantly decrease tissue HMG-1 mRNA expression in the liver and lung (P < 0.01). In addition, there were high positive correlations between hepatic HMG-1 mRNA and serum aminoleucine transferase (ALT) and aspartate aminotransferase (AST) levels, and also between pulmonary HMG-1 mRNA and myeloperoxidase activities (P < 0.05-0.01). Taken together, these findings indicate that thermal injury per se can markedly enhance HMG-1 gene expression in various organs. Up-regulation of HMG-1 expression may be involved in the pathogenesis of endogenous endotoxin-mediated multiple organ damage secondary to major burns.
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PMID:The significance of changes in high mobility group-1 protein mRNA expression in rats after thermal injury. 1195 36

The effect of higenamine, a benzyl-tetrahydroisoquinoline alkaloid of the roots of Aconitum spp. (Ranunculaceae), on disseminated intravascular coagulation (DIC), was investigated using an experimental DIC rat model. The oral administration of higenamine (10 mg/kg or 50 mg/kg), significantly ameliorated the decrease of fibrinogen level in plasma, the increase of fibrinogen/fibrin degradation product (FDP) level, and the prolongation of prothrombin time (PT) induced by the i. v. infusion of lipopolysaccharide (LPS). The prolongation of activated partial thrombin time (aPTT) and the decrease of platelet count were suppressed. The increase in serum aspartate aminotransferase (AST) and blood urea nitrogen (BUN) were also significantly prevented with higenamine. The above results are suggestive that higenamine has therapeutic potential for DIC and/or accompanying multiple organ failure (MOF).
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PMID:The effects of higenamine on LPS-induced experimental disseminated intravascular coagulation (DIC) in rats. 1198 56

Aflatoxin B(1) (AFB(1)) is a fungal toxin that causes both acute hepatotoxicity and hepatocellular carcinoma in humans and experimental animals. Previous studies demonstrated that a small, noninjurious dose of bacterial lipopolysaccharide (LPS) augments the hepatotoxicity of AFB(1) through activation of inflammatory cells and production of soluble inflammatory mediators (Barton et al., 2000b, 2001). This study was conducted to examine the effect of LPS on the dose-response relationship for AFB(1)-induced liver injury. Male Sprague-Dawley rats (250-350g) were treated with AFB(1) (0.1 mg/kg-6.3 mg/kg, ip) and 4 h later with a noninjurious dose of E. coli LPS (7.4 x 10(6) EU/kg, iv). Twenty-four h after AFB(1) administration, hepatic parenchymal cell injury was estimated from elevations in serum alanine aminotransferase and aspartate aminotransferase activities. Injury to intrahepatic bile ducts was evaluated from increased serum gamma-glutamyl transferase and alkaline phosphatase activities. Based on benchmark dose (BMD) analysis, the AFB(1) BMD for parenchymal cell injury was decreased 10-fold by LPS cotreatment, whereas AFB(1) BMDs for bile duct injury were decreased nearly 20-fold. The data suggest that concurrent inflammation renders the liver considerably more sensitive to the hepatotoxic effects of AFB(1).
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PMID:Bacterial lipopolysaccharide exposure alters aflatoxin B(1) hepatotoxicity: benchmark dose analysis for markers of liver injury. 1207 24

Cocaine produces hepatotoxicity by a mechanism that remains undefined but that has been linked to its oxidative metabolism. Endotoxin (lipopolysaccharide, LPS) is also a well-known cause of hepatic damage, where exposure to non-injurious doses of LPS increases the toxicity of certain hepatotoxins. This study was conducted to investigate the possible potentiation of cocaine-mediated hepatotoxicity (CMH) by LPS. Male CF-1 mice were administered oral cocaine hydrochloride for 5 consecutive days at a dose of 20 mg/kg with and without 12 x 10(6) EU LPS/kg given intraperitoneally 4 h after the last cocaine injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured as markers of liver injury. Blood and liver glutathione (GSH) levels were determined, as well as the activities of glutathione peroxidase (GPx) and catalase (CAT). In addition, the activity of liver glutathione reductase (GRx) was measured. The results demonstrate that endotoxin potentiated the hepatotoxicity of cocaine. Serum ALT and AST were significantly elevated with the combined cocaine and LPS treatment versus all other treatments. While cocaine alone resulted in centrilobular necrosis, the cocaine and LPS combination produced submassive necrosis. The increased hepatic GSH content and GRx activity observed with cocaine alone were not observed with the combination treatment, rendering the liver more susceptible to oxidative stress. Moreover, there was a significant decrease in the activities of hepatic GPx and CAT, particularly with the combination treatment. In conclusion, this study demonstrates that LPS potentiates the hepatotoxicity of cocaine as revealed by an array of biochemical and morphological markers.
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PMID:Endotoxin potentiates the hepatotoxicity of cocaine in male mice. 1213 32

The oxidative metabolism of cocaine by the microsomal monooxygenase enzymes has been postulated to be essential for cocaine mediated hepatotoxicity (CMH). Endotoxin (lipopolysaccharide, LPS), a well-known cause of hepatic damage, previously has been demonstrated to dramatically increase CMH. The mechanism of this interaction has not been clearly elucidated, but cocaine oxidative metabolism appears to sensitize hepatocytes so that subsequent exposure to small amounts of LPS can further augment CMH. This study was conducted to investigate if dimethylaminoethyl-2,2-diphenylvalerate (SKF-525A) pretreatment inhibits LPS potentiation of CMH. For 5 consecutive days, male CF-1 mice were administered daily SKF-525A (50 mg/kg) or sterile saline followed an hour later by cocaine (20 mg/kg) or sterile saline. Four hours following the last cocaine or saline treatment, the mice were administered sterile saline 12x10(6) EU LPS/kg, i.p. The mice were sacrificed 18 h later by decapitation. Pretreatment with SKF-525A reversed the hepatic injury caused by cocaine alone or cocaine and LPS treatments, as indicated by both histologic evaluation and serum alanine transaminase (ALT) and aspartate transaminase (AST) activities. In particular, SKF-525A completely reversed the effects of cocaine alone on liver and blood reduced gluthathione (GSH), glutathione peroxidase (GPx) and catalase (CAT) and hepatic glutathione reductase (GRx) activities. However, SKF-525A was ineffective against the effect of LPS alone on liver and blood GPx and CAT or on hepatic GSH and GRx, suggesting that these effects were not mediated by cytochrome P450 oxidative metabolism. The pattern of biochemical changes persisting with SKF-525A pretreatment in the LPS and cocaine group resembled those of the LPS alone group. The results suggest that cytochrome P450 oxidative metabolism of cocaine is largely responsible for CMH with potentiation by LPS achieved through a different mechanism involving oxidative stress.
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PMID:Inhibition of cocaine oxidative metabolism attenuates endotoxin potentiation of cocaine mediated hepatotoxicity. 1220 38

Using a rat model of septic shock we studied the effects of Evodia rutaecarpa, a Chinese herbal medicine with antimicrobial and anti-inflammatory activity, on haemodynamic parameters, biochemical markers of organ function and nitric oxide (NO) production. Anaesthetized rats challenged with a high dosage of endotoxin (Escherichia coli lipopolysaccharide; LPS; 50 mg kg(-1), i.v.) for 6 h showed a severe decrease in mean arterial pressure. This was accompanied by delayed bradycardia, vascular hyporeactivity to phenylephrine and increase in plasma levels of lactate dehydrogenase, aspartate aminotransferase, bilirubin and creatinine, as well as NOx (NO2- plus NO3-). Pretreatment with ethanol extract of E. rutaecarpa (25, 50 and 100 mg kg(-1), i.v.), 1 h before LPS, dose-dependently prevented the circulation failure, vascular hyporeactivity to phenylephrine, prevented liver dysfunction and reduced the NOx over-production in plasma in endotoxaemic rats. A selective inducible NO-synthase (iNOS) inhibitor, aminoguanidine (15 mg kg(-1), i.v.), also effectively ameliorated the above pathophysiological phenomenon associated with endotoxaemia so that the normal condition was approached. Endotoxaemia for 6 h resulted in a significant increase in iNOS activity in the liver homogenate, which was attenuated significantly by E. rutaecarpa pretreatment. In summary, E. rutaecarpa, at the dosages used, exerted these beneficial effects probably through inhibition of iNOS activity and subsequent modulation of the release of NO. These significant results may offer E. rutaecarpa as a candidate for the treatment of this model of endotoxaemia.
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PMID:Evodia rutaecarpa protects against circulation failure and organ dysfunction in endotoxaemic rats through modulating nitric oxide release. 1239 3

OBJECTIVE: To investigate the protective and jaundice-relieving effects of gentiopicrooside (GPS) injections in mouse and rat models of chemical-induced and immune-mediated hepatic injury. METHODS: Mouse models of chemical-induced liver injury were established by CCl4 injections into the abdominal cavity, mouse models of immune-mediated liver damage by bacillus Calmette-Guerin (BCG) and lipopolysaccharide (LPS) and rat models of jaundice by oral alpha-naphthyliso-thiocyanate (ANIT). Treatment with GPS injections was administered and both of enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the Serum were measured in the models. The serum level of total bilirubin was determined in the jaundice models. RESULTS: Compared with those of the untreated models, the enzyme activities of ALT and AST were significantly reduced in groups with a 10 day GPS treatment (P<0.001, P<0.05). Higher dosage of GPS showed more conspicuous effects in relieving the jaundice. CONCLUSION: GPS can be administered as the antagonist against CC14-induced liver injury and offers protection against immune-mediated liver damage.
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PMID:Effects of gentiopicrooside injections on experimental hepatic injury. 1242 61

Effects of dietary protein type on lipopolysaccharide (LPS)-induced hepatitis, as assessed by plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, were investigated in D-galactosamine (GalN)-sensitized rats. The plasma ALT and AST activities in rats fed on 25% soybean protein isolate (SPI) diet were significantly suppressed to about 1/4 and 1/5 of the values in rats fed on 25% casein diet, respectively, 8 h after the injection of LPS + GalN. Although hepatic ALT and AST activities of normal rats were also lower in the SPI group than in the casein group, this could not explain the differences in plasma enzyme activities between the two groups. The hepatic glutathione concentration of normal rats was lower in the SPI group than in the casein group, but it was reversed in rats injected with drugs. The results suggest that SPI can protect animals from LPS + GalN-induced hepatitis, and that the hepatic glutathione level may participate in the effects of SPI.
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PMID:Differential effects of dietary casein and soybean protein isolate on lipopolysaccharide-induced hepatitis in D-galactosamine-sensitized rats. 1245 Jan 39

Hibiscus protocatechuic acid (PCA), a phenolic compound found in the dried flowers of Hibiscus sabdariffa L. (Malvaceae), was demonstrated to have an antioxidant effect in vitro and in vivo, and an antitumor property in our previous study. In the present study, we used lipopolysaccharide (LPS, an endotoxin) to induce rat liver inducible nitric oxide synthase (iNOS), and found that pretreatment with PCA decreased the liver iNOS and the serum total nitrite induced by LPS. Our investigation showed that pretreatment of rats with PCA (0.2 and 0.5 mmol/kg dosed by gavage) for 5 days significantly decreased the serum levels of the hepatic enzyme markers alanine- and aspartate aminotransferase (ALT, alanine aminotransferase; AST, aspartate aminotransferase) induced by the 6-h treatment with LPS (i.p.; 5 mg/kg). Histopathological evaluation of the rat livers revealed that PCA reduced the incidence of liver lesions induced by LPS, including neutrophil infiltration, congestion, and liver cell swelling induced by LPS in rats. We conclude that PCA, an antioxidant, presents an inhibitory potential on iNOS and hepatic damage induced by LPS.
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PMID:Hibiscus protocatechuic acid inhibits lipopolysaccharide-induced rat hepatic damage. 1249 Oct 40


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