As a dangerous disease with rapid progression, endotoxemia is easy to induce the damage to multiple organs. However, its specific and efficient treatment methods are still lacking at present. Both Qingkailing Injection(QKLI) and Shengmai Injection(SMI) have been proved effective in anti-inflammation, anti-endotoxin and organ protection. In this study, carrageenan and endotoxin were injected successively into rats to establish an endotoxemia model. Different doses of QKLI and SMI were administered to the endotoxemia rats by intraperitoneal injection separately or in combination. Then the count of white blood cells, the number of platelets, the content of cytokines, biochemical indexes, organ coefficient and pathological changes of main organs in the rats were detected. The results showed that the rats in the model group had obvious symptoms of endotoxemia, i.e., leucopenia, thrombocytopenia, increase in cytokines(IL-6 and TNF-α) and biochemical indexes of liver and kidney function as well as pathological damage to liver, kidney and lung. QKLI alone can alleviate the above symptoms of endotoxemia and the organ injury. SMI alone is less effective in improving disseminated intravascular coagulation(DIC) and cytokine secretion complicated with endotoxemia, but capable of reducing the inflammation degree of the lung, liver and kidney. The combination of QKLI and SMI remarkably increased the number of platelets in the peripheral blood, improved the liver and kidney function and reduced inflammatory factors, with lung, liver, kidney and other organ structures protected well. Moreover, the improvement effect of the combination of QKLI and SMI was stronger than those of the two injections alone at fixed doses, indicative of a synergistic effect.
Animals ; Drug Combinations ; Drugs, Chinese Herbal ; Endotoxemia/drug therapy* ; Rats

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endotoxemia ; blood ; drug therapy ; immunology ; Humans ; Lipopolysaccharide Receptors ; blood ; Lipopolysaccharides ; blood ; Phytotherapy ; Shock, Septic ; blood ; drug therapy ; immunology

OBJECTIVETo observe the antifebrile effect of Naoreqing (NRQ) oral liquid on secretive function of vaso-endothelial cells in rabbits with endotoxic fever.

METHODSEndotoxic fever rabbit model was duplicated to observe the effects of NRQ on body temperature, blood levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and endothelin (ET) using radioimmunoassay, as well as activity of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in plasma by chromophoric substrate assay.

RESULTSComparisons of various indexes between the two groups showed significantly difference, i.e. the maximal increment of body temperature: 0.69 +/- 0.07 degrees C vs 1.31 +/- 0.13 degrees C (the NRQ treated group vs the untreated model group, the same hereafter); 2h thermal response index TRI2 4.85 +/- 0.57 vs 8.44 +/- 0.98; plasma ET content 197.96 +/- 39.11 ng/L vs 250.80 +/- 40.99 ng/L; TXB2 content 177.35 +/- 77.30 ng/L vs 279.64 +/- 83.74 ng/L; activity of PAI 0.84 +/- 0.01AU/ml vs 0.86 +/- 0.01 AU/ml; plasma 6-keto-PGF1alpha content 986.70 +/- 327.36 ng/L vs 507.81 +/- 170.01 ng/L; activity of t-PA 0.25 +/- 0.02 IU/ml vs 0.21 +/- 0.02 IU/ml (P < 0.05, P < 0.01).

CONCLUSIONNRQ may improve secretive function of vaso-endothelial cells to dilate blood vessel and quicken heat dissipation through body surface, so as to play an integral antipyretic effect in rabbits with endotoxic fever.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Endothelium, Vascular ; drug effects ; secretion ; Endotoxemia ; complications ; Fever ; drug therapy ; etiology ; Male ; Phytotherapy ; Rabbits ; Random Allocation

The aim of the present study was to investigate the effects of sodium butyrate (SB) on systemic inflammation, lung injury and survival rate of mice with endotoxemia. Balb/c mice were pre-treated with SB or vehicle, and then endotoxemia was induced by lethal dose of lipopolysaccharide (LPS, 20 mg/kg, i.p.) and the survival rate of mice was monitored. A separated set of animals were sacrificed at 18 h after LPS challenge, and blood samples were harvested for measuring TNF-α and IL-6 levels. Lung tissues were also harvested to determine the ratio of wet weight to dry weight of lung tissue and myeloperoxidase (MPO) activity in lung tissue. In addition, the formalin-fixed lung specimens were stained with HE routinely for morphologic evaluation. The results showed that pre-treatment with SB alleviated LPS-induced morphological damage in lung tissue. This was accompanied by reduced ratio of wet weight to dry weight of lung tissue and MPO activity in lung homogenates. Additionally, the up-regulation of pro-inflammatory cytokines TNF-α and IL-6 was also suppressed by SB, while the survival rate of mice with lethal endotoxemia was significantly increased by SB pre-treatment. The results suggest that SB effectively attenuates intrapulmonary inflammatory response and improves the survival of endotoxemic mice.
Animals ; Butyric Acid ; pharmacology ; Endotoxemia ; drug therapy ; Inflammation ; drug therapy ; Interleukin-6 ; metabolism ; Lipopolysaccharides ; Lung ; drug effects ; pathology ; Lung Injury ; drug therapy ; Male ; Mice ; Mice, Inbred BALB C ; Peroxidase ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo study whether previously intravenous injection of anisodamine can prevent endotoxemia of heat stroke of rats.

METHODSExperimental animals were randomly divided into two groups, their average artery pressure, heart rate, survival time, survival rate and rectal temperature were measured at an environmental temperature of 38 degrees C-40 degrees C and 50%-60% retative humidity. Blood samples for endotoxins analyses were taken both before and after heat-stress.

RESULTSDuring heat stress, the animals of rectal temperature of the experimental and control groups continuously increased and two hours later, separately to (42.7 +/- 0.6) degree C and (43.1 +/- 0.5) degree C, without statistic difference(P > 0.05), and to (44.6 +/- 0.4) degree C and (44.2 +/- 0.3) degree C prior to death, with statistic difference(P < 0.05). Before the experiment, the contents of endotoxins of portal vein blood were (45.7 +/- 5.2) pg/ml and (42.6 +/- 5.4) pg/ml, and that of systemic blood was (14.8 +/- 4.5) pg/ml and (13.9 +/- 7.2) pg/ml, without statistic difference(P > 0.05). Two hours later, the contents of portal vein blood separately increased to (122.2 +/- 16.7) pg/ml and (49.7 +/- 10.2) pg/ml, obviously higher than that before heat-stress(P < 0.01). And there were clear statistic difference between the two groups(P < 0.01). The changing tendency of the heart rhythm is almost the same in two groups, that is, first rose and then fell. But it is without statistic difference before and two hours later(P > 0.05): before heat-stress, the average artery pressures were (13.3 +/- 0.6) kPa and (13.6 +/- 0.5) kPa, without statistic difference(P > 0.05), and two hours later, were (9.6 +/- 0.5) kPa and (8.6 +/- 0.6) kPa, with obvious statistic difference(P < 0.01). The survival time of the animals were (166.5 +/- 16.9) min and (144.5 +/- 18.2) min with obvious statistic difference(P < 0.01), the survival rate of heat stressed rats in the experimental group were obviously higher than control group(P < 0.01 or P < 0.05).

CONCLUSIONSAnisodamine can prevent endotoxemia in rats suffering heat stroke.

Animals ; Blood Pressure ; Body Temperature ; Endotoxemia ; prevention & control ; Endotoxins ; blood ; Heat Stress Disorders ; drug therapy ; mortality ; physiopathology ; Hot Temperature ; Rats ; Solanaceous Alkaloids ; therapeutic use ; Survival Rate

OBJECTIVETo investigate the changes in the plasma levels of endotoxin in severe burn patients during administration of antibiotics.

METHODSFifty severe burn patients with burn area larger than 30% TBSA were enrolled in the study, and they were respectively treated with Netilmicin (A group), Cefoperazone (B group), Ceftazidime (C group) and Imipenem/Cilastatin (D group). Venous blood samples were harvested for determination of endotoxins levels before treatment and 1, 2, 3, 5, 7 post-treatment day (PTD).

RESULTSThe plasma levels of endotoxin were elevated in different degrees in A, B and C groups. The plasma levels of endotoxin in B group were higher on 1, 2 PTD than on 3, 5, 7 PTD, and they were also higher than that in D group (P < 0.05). The plasma levels of endotoxin in C group reached the peak on 5 PTD [(0.398 +/- 0.172) EU/mL], which were higher than that before treatment [(0.251 +/- 0.142) EU/mL, P < 0.05] and other groups (P < 0.05). The plasma levels of endotoxin in D group were lower on 1, 2 PTD than that before treatment (P < 0.05).

CONCLUSIONDifferent amounts of endotoxins can be released after treatment with antibiotics in severe burn patients. Attention should be paid to the effect of antibiotics on the levels of endotoxin in practice.

Adolescent ; Adult ; Anti-Bacterial Agents ; therapeutic use ; Burns ; blood ; drug therapy ; Endotoxemia ; etiology ; Endotoxins ; blood ; Female ; Humans ; Male ; Middle Aged ; Plasma ; Young Adult

BACKGROUND: Antitumor drugs such as 5-fluorouracil (5-FU) are known to induce intestinal damages and bacterial translocation. The present studies examined whether or not bovine colostrum protects against gut barrier damage, bacterial translocation and endotoxemia from these antitumor drugs. METHODS: Rat received either no drug, chemotherapy alone (5-FU, 300 mg/kg intraperitoneal injection) or bovine colostrum (4 g/day per os) for 5 days prior to 5-FU and for 5 days afterward. Intestinal permeability, enteric aerobic bacterial counts, serum albumin and protein levels, and pathologic findings of ileum were measured. Bacterial translocation to systemic blood, mesenteric lymph nodes, liver and spleen were measured. Systemic plasma endotoxin levels were quantified by the chromogenic limulus amebocyte lysate (LAL) technique. RESULTS: 5-FU increase intestinal permeability and plasma endotoxin levels, and decreased serum levels of total protein and albumin. Also 5-FU induced bacterial translocation to mesenteric lymph nodes, liver and spleen, not to systemic blood, but did not induce changes of enteric bacterial numbers and mucosal damages of small intestine. Combined administration of bovine colostrum with 5-FU reduced an increase in intestinal permeability and declines in serum albumin and protein levels by 5-FU. Bovine colostrum supplements also reduced bacterial translocation to mesenteric lymph nodes, liver and spleen, and endotoxemia. CONCLUSION: Bovine colostrums may beneficial effects in preventing 5-FU induced gut barrier damage, bacterial translocation and intestinal endotoxemia.
Animals ; Antineoplastic Agents ; Bacterial Load ; Bacterial Translocation* ; Colostrum* ; Drug Therapy ; Endotoxemia* ; Endotoxins ; Fluorouracil* ; Horseshoe Crabs ; Ileum ; Intestine, Small ; Liver ; Lymph Nodes ; Permeability ; Plasma ; Rats* ; Serum Albumin ; Spleen

BACKGROUNDAcute lung injury/acute respiratory distress syndrome presents with not only local inflammation, but also pulmonary coagulopathy which is characterized by an alveolar procoagulant response, anticoagulant inhibition, fibrinolytic supression and fibrin deposition. We thus had hypothesized that if aerosolized unfractionated heparin was inhaled into alveolar spaces, it could block the procoagulant tendency, lessen depletion of coagulation factors, and even influence the inflammatory response. We also assessed the effects of different administration regimens of heparin.

METHODSMale Wistar rats were given inhaled heparin starting 30 minutes before (prophylactic heparin) or 2 hours after (therapeutic heparin) intravenous lipopolysaccharide (LPS) was administered at 6-hour intervals; control groups received inhaled normal saline with or without being exposed to LPS. Thrombin-antithrombin complexes, activated protein C, tissue type and urokinase type plasminogen activators (t-PA/u-PA), plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α, interleukin-6 in bronchoalveolar lavage, and lung tissue myeloperoxidase activity, and histology score were measured at three time-points. PAI-1/(t-PA + u-PA) was calculated based on the before-mentioned parameters. Statistical analysis was made using one-way analysis of variance (ANOVA) with post hoc test or Student's t test in the case of heterogeneity of variance.

RESULTSAn alveolar procoagulant reaction, depressed fibrinolysis, and inflammatory response occurred in endotoxemia-induced lung injury. Local prophylactic application of heparin attenuated coagulation and early inflammation, promoted fibrinolysis, and reduced the histology score. Therapeutic application of heparin had similar, but weaker effects.

CONCLUSIONSIntrapulmonary application of unfractionated heparin by inhalation might inhibit alveolar procoagulant reaction and the early inflammatory response, promote fibrinolysis, and alleviate pulmonary pathology in endotoxemia-induced lung injury rats. Administration of heparin before LPS challenge was more efficacious.

Acute Lung Injury ; blood ; drug therapy ; Administration, Inhalation ; Animals ; Blood Coagulation ; drug effects ; Endotoxemia ; complications ; Fibrinolysis ; drug effects ; Heparin ; administration & dosage ; Inflammation ; drug therapy ; Lung ; pathology ; Male ; Rats ; Rats, Wistar

BACKGROUNDTreatment with melatonin significantly reduces lung injury induced by bleomycin, paraquat and ischemia reperfusion. In the present study, we investigated the possible protective roles of melatonin in pulmonary inflammation and lung injury during acute endotoxemia.

METHODSThirty-two male Sprague-Dawley rats were randomly assigned to four groups: vehicle + saline group, melatonin + saline group, vehicle + lipopolysaccharide group, melatonin + lipopolysaccharide group. The rats were treated with melatonin (10 mg/kg, intraperitoneal injection (i.p.)) or vehicle (1% ethanol saline), 30 minutes prior to lipopolysaccharide administration (6 mg/kg, intravenous injection). Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Blood gas analysis was carried out. Optical microscopy was performed to examine pathological changes in lungs and lung injury score was assessed. Wet/dry ratios (W/D), myeloperoxidase activity, malondialdehyde concentrations and tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) levels in lungs were measured. The pulmonary expression of nuclear factor-kappa B (NF-kappaB) p65 was evaluated by Western blotting.

RESULTSPaO(2) in the vehicle + lipopolysaccharide group decreased compared with that in the vehicle + saline group. This decrease was significantly reduced in the melatonin + lipopolysaccharide group. The lung tissues from the saline + lipopolysaccharide group were significantly damaged, which were less pronounced in the melatonin + lipopolysaccharide group. The W/D ratio increased significantly in the vehicle + lipopolysaccharide group (6.1 +/- 0.18) as compared with that in the vehicle + saline group (3.61 +/- 0.3) (P < 0.01), which was significantly reduced in the melatonin + lipopolysaccharide group (4.8 +/- 0.25) (P < 0.01). Myeloperoxidase activity and malondialdehyde levels increased significantly in the vehicle + lipopolysaccharide group compared with that in the vehicle + saline group, which was reduced in the melatonin + lipopolysaccharide group. The TNF-alpha level of pulmonary tissue increased significantly in the vehicle + lipopolysaccharide group ((8.7 +/- 0.91) pg/mg protein) compared with that in the vehicle + saline group ((4.3 +/- 0.62) pg/mg protein, P < 0.01). However, the increase of TNF-alpha level of pulmonary tissue was significantly reduced in the melatonin + lipopolysaccharide group ((5.9 +/- 0.56) pg/mg protein, P < 0.01). Pulmonary IL-10 levels were elevated markedly in the vehicle + lipopolysaccharide group in contrast to that in the vehicle + saline group, whereas the elevation was augmented in the melatonin + lipopolysaccharide group. The nuclear localization of p65 increased markedly in the vehicle + lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the melatonin + lipopolysaccharide group.

CONCLUSIONMelatonin reduces acute lung injury in endotoxemic rats by attenuating pulmonary inflammation and inhibiting NF-kappaB activation.

Acute Lung Injury ; drug therapy ; pathology ; Animals ; Blotting, Western ; Endotoxemia ; drug therapy ; physiopathology ; Interleukin-10 ; metabolism ; Lipopolysaccharides ; toxicity ; Lung ; drug effects ; metabolism ; Male ; Melatonin ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

Animals ; Astragalus membranaceus ; Endotoxemia ; drug therapy ; metabolism ; Interferon-gamma ; analysis ; Interleukin-4 ; analysis ; Male ; Mice ; Phytotherapy ; Plant Extracts ; therapeutic use ; Th1 Cells ; drug effects ; metabolism ; Th2 Cells ; drug effects ; metabolism