Endotoxemia ; diagnosis ; Endotoxins ; analysis ; Humans ; Sepsis ; diagnosis

Over the past decade, growing evidence has established the gut microbiota as one of the most important determinants of metabolic disorders such as obesity and type 2 diabetes. Indeed, obesogenic diet can drastically alter bacterial populations (i.e., dysbiosis) leading to activation of pro-inflammatory mechanisms and metabolic endotoxemia, therefore promoting insulin resistance and cardiometabolic disorders. To counteract these deleterious effects, probiotic strains have been developed with the aim of reshaping the microbiome to improve gut health. In this review, we focus on benefits of widely used probiotics describing their potential mechanisms of action, especially their ability to decrease metabolic endotoxemia by restoring the disrupted intestinal mucosal barrier. We also discuss the perspective of using new bacterial strains such as butyrate-producing bacteria and the mucolytic Akkermansia muciniphila, as well as the use of prebiotics to enhance the functionality of probiotics. Finally, this review introduces the notion of genetically engineered bacterial strains specifically developed to deliver anti-inflammatory molecules to the gut.
Bacteria ; Diet ; Endotoxemia ; Insulin Resistance ; Microbiota ; Obesity ; Prebiotics ; Probiotics*

Background: It has been reported that steroid and lidocaine reduce inflammatory responses to endotoxin. The aim of this study is to compare the effects of lidocaine with those of steroid on inflammatory responses to Escherichia coli endotoxemia in the rabbit lung. Methods: Twenty four animals were randomly assigned to one of four groups. Group I (endotoxemic group; control, n=6): They were received E. coli endotoxin (500 microg/kg) intravenously through the ear vein and followed by saline infusion at 20 ml/kg/hr for 4 hours. Group II (steroid treated group, n=6): They were treated with steroid (30 mg/kg) intravenously just after endotoxin injection and then saline was given at 20 ml/kg/hr for 4 hours. Group III (lidocaine treated group, n=6): They were received same as the endotoxemic group and lidocaine (3 mg/kg IV bolus, then continuous infusion at the rate of 2 mg/kg/hr) was administered with saline at 20 ml/kg/hr for 4 hours. Group IV (steroid & lidocaine treated group, n=6): They were received same as the endotoxemic group and after endotoxin infusion, steroid (30 mg/kg) and lidocaine (3 mg/kg IV bolus, then continuous infusion at the rate of 2 mg/kg/hr) was administered intravenously with saline. Numbers of neutrophils and monocytes in the samples of peripheral blood and lung tissue were counted and compared to evaluate the anti-inflammatory effect of drugs. Results: The group II, III, and IV showed significant attenuation of inflammatory responses compared to group I in the rabbit lung(P<0.05). But there were no significant differences among group II, III, and IV. There was no additive effect between steroid and lidocaine. Conclusion: These results suggest that lidocaine could be used as an alternative drug to steroid for its anti-inflammatory effects and cost-effectiveness.
Animals ; Ear ; Endotoxemia* ; Escherichia coli ; Lidocaine* ; Lung* ; Monocytes ; Neutrophils ; Veins

Endotoxemia ; metabolism ; pathology ; HMGB1 Protein ; Humans ; Liver ; metabolism ; pathology

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

BACKGROUND/AIMS: Early intestinal mucosal damage plays an important role in severe acute pancreatitis (AP). Previous studies have shown that intestinal permeability (IP), serum endotoxin and cytokines contribute to the early intestinal barrier dysfunction in AP. This study explored the predictive capacity of IP, endotoxemia and cytokines as prognostic indicators in AP patients. METHODS: Eighty-seven AP patients were included in the study. The patients were classified into three groups according to the Balthazar computed tomography severity index (CTSI). We compared the biochemical parameters, including IP, serum endotoxin level and cytokine level among the three groups. The associations of IP with serum endotoxin, cytokines, CTSI, and other widely used biochemical parameters and scoring systems were also examined. RESULTS: IP, serum endotoxin, interleukin (IL-6) and tumor necrosis factor (TNF)-alpha had a positive correlation with the CTSI of AP. Endotoxin, IL-6, TNF-alpha, CTSI, the Ranson/APACHE II score, the duration of hospital stay, complications and death significantly affect IP in the AP patients. CONCLUSIONS: We believe that IP with subsidiary measurements of serum endotoxin, IL-6 and TNF-alpha may be reliable markers for predicting the prognosis of AP. Further studies that can restore and preserve gut barrier function in AP patients are warranted.
Cytokines ; Endotoxemia ; Endotoxins ; Humans ; Interleukin-6 ; Interleukins ; Length of Stay ; Pancreatitis ; Permeability ; Prognosis ; Tumor Necrosis Factor-alpha

PURPOSE: We conducted this study to assess the effect of oral application of bovine colostrum on the plasma endotoxin and TNF-alpha following the abdominal surgery. METHODS: 46 patients who underwent the abdominal surgery were evenly enrolled in a prospective, randomized, double blind and placebo-controlled study. The patients were preoperatively managed by oral application of 20 g of a bovine colostrums or placebo (nonfat dried milk) per a day for 3 days. In both groups, endotoxin was sequentially determined pre-, intra- and postoperatively by a modified limulus amebocyte lysate test. TNF-alpha and CRP were also measured. The clinical course was followed and compared in both groups. RESULTS: The colostrum group showed significantly lower level of endotoxin and TNF-alpha compared to the placebo group. CRP did not differ in both groups. Clinical event did not occur in both group until the discharge. Colostrum group tends to have a lower incidence of fever and leukocytosis without statistic significance. CONCLUSION: Prophylactic preoperative oral application of bovine colostrum lower the plasma level of perioperative endotoxin and TNF-alpha. Further studies were needed for the relation of clinical effect and preoperative oral application of bovine colostrum.
Colostrum* ; Endotoxemia* ; Fever ; Horseshoe Crabs ; Humans ; Incidence ; Leukocytosis ; Plasma ; Prospective Studies ; Tumor Necrosis Factor-alpha*

Endotoxemia ; complications ; Endotoxins ; metabolism ; Humans ; Liver Diseases, Alcoholic ; complications ; Signal Transduction

OBJECTIVEEndotoxemia is a serious syndrome resulting in multi-organ failure. Once it happens, the penetration of small intestine epithelium increases, body liquid losses, then effective circulating blood decreases and serious metabolic acidosis, serious hypotension, systolic failure, and even shock may occur. In this pathological process, endotoxin, tumor necrosis alpha and systolic dysfunction play important roles. Nowadays, many studies have been done to resolve the systolic dysfunction, but too much attention had been paid to the followings: the depressions of myocardium caused by tumor necrosis alpha, other inflammatory factors, endotoxin and metabolic acidosis; the disturbance of blood vessel-nerve regulations; nitric oxide (NO)/inducible nitric oxide synthase (iNOS) over-synthesis and the decreased density of beta-receptors in the myocardium and/or their activities. Little attention has been paid to the relationship between alpha sarcmeric actin (alpha-SA) and systolic dysfunction during endotoxemia. Glutamine (Gln) can be metabolized into glutathione, an eliminator of free radical. It has been used in preventing myocardial damage from reperfusion. This study aimed to observe the dynamic changes of alpha-SA and mRNA expressions in rats with endotoxemia and examine the effects of Gln on them.

METHODSClassical rat model of endotoxemia was established by intraperitoneal injection of LPS (4 mg/kg, Escherichia coli O55:B5, Sigma). 121 Wistar 18-day-rats were divided into three groups randomly, (1) 0 h control group (normal saline: 1 ml/kg, n = 11). (2) LPS group (LPS: 4 mg/kg, n = 55). (3) Gln group (LPS: 4 mg/kg and immediately 13.64%; Gln: 1 ml/kg, Fresenus, n = 55), Furthermore, LPS and Gln groups were divided into 2, 4, 6, 24 and 72 h time points (n = 11). Each time point of LPS and Gln as well as control rats were anaesthetized at each time point with 1% chloral hydrate injected intraperitoneally at the dosage of 1 ml/kg. Then rats were sacrificed at appoint time, and the hearts were isolated. Eight of them were put in 76 degrees C liquid nitrogen and then frozen in minute 80 degrees C icebox in order to measure the expression of alpha-SA mRNA by RT-PCR. Three of them were fixed in 4% formaldehydum polymerisatum for 12 to 16 h, then the expression of alpha-SA was detected by immunohistochemistry.

RESULTS(1) Compared to 0 h, the expressions of alpha-SA and mRNA in LPS group were significantly depressed (P < 0.01). In LPS group, the lowest was at 6 - 24 h, while in Gln group, it was postponed to 24 h. At 72 h, there was no difference in expressions of alpha-SA between Gln and 0 h group (P > 0.05). (2) Comparing at same time point, the expressions of alpha-SA were significant higher in Gln group than those in LPS group, while the expressions of alpha-SA mRNA in Gln group were high at 4-72 h. There was, however, no significant difference at early phase (P > 0.05).

CONCLUSIONAlpha-SA and its mRNA expression were depressed in LPS-induced endotoxemia, especially from 6 to 24 h. It could damage the systolic function. alpha-SA decrease in endotoxemia was due to the inhibited synthesis other than the promoted degradation. Glutamine could inhibit the effects of LPS on both alpha-SA and its mRNA expressions.

Actins ; metabolism ; Animals ; Endotoxemia ; metabolism ; Glutamine ; pharmacology ; Lipopolysaccharides ; Myocardium ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar

BACKGROUND: Sepsis, surgical stress, and anesthesia are often associated with postoperative immune suppression and an increased susceptibility to infection. Apoptosis is an important mechanism of cell death in sepsis and Endotoxemia, and the apoptosis-induced loss of lymphocytes may be responsible for immune depression. To access the possible role of propofol on human immune function in sepsis, we investigated the apoptosis of mononuclear cells (MNCs) and lymphocyte from peripheral blood. METHODS: Healthy human mononuclear cells were isolated and stimulated with lipopolysaccharide (LPS) for 5 hrs. And, activated MNCs were cultured in the presence of varying concentrations of propofol (1 microgram/ml, 5 microgram/ml, 10 microgram/ml and 50 microgram/ml) for 20 hrs. The apoptotic indices of LPS-treated MNCs, monocytes and lymphocytes were calculated by flow cytometry using an Annexin-V-FLUOS staining kit. RESULTS: Propofol exposure at 1, 5 and 10 microgram/ml did not significantly affect apoptosis of the LPS-treated MNCs, monocytes or lymphocytes, but a concentration of 50 microgram/ml increased the apoptosis of MNCs and lymphocytes significantly (P < 0.01). CONCLUSIONS: Since the concentrations of propofol used were in the clinically acceptable range for sedation and anesthesia, this result suggests that propofol does not significantly alter the apoptosis of NMCs, monocytes or lymphocytes in septic conditions for up to 20 hrs.
Anesthesia ; Apoptosis* ; Cell Death ; Depression ; Endotoxemia ; Flow Cytometry ; Humans ; Lymphocytes* ; Monocytes ; Propofol* ; Sepsis