Alterations of systemic endotoxemia over the course of acute edematous pancreatitis

Pancreatology ◽  
2003 ◽  
Vol 3 (4) ◽  
pp. 323-328 ◽  
Author(s):  
Evangelos J. Giamarellos-Bourboulis ◽  
George C. Nikou ◽  
Maria Matsaggoura ◽  
Christos Toumpanakis ◽  
Paraskevi Grecka ◽  
...  
Keyword(s):  
Edematous Pancreatitis ◽  
Systemic Endotoxemia

scholarly journals Necroptosis protects against exacerbation of acute pancreatitis

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Michittra Boonchan ◽  
Hideki Arimochi ◽  
Kunihiro Otsuka ◽  
Tomoko Kobayashi ◽  
Hisanori Uehara ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Necrotizing Pancreatitis ◽  
Neutrophil Infiltration ◽  
Dependent Manner ◽  
Protective Effects ◽  
Interacting Protein ◽  
Inflammatory Conditions ◽  
Edematous Pancreatitis ◽  
Genetic Deletion ◽  
Dose Dependent

AbstractThe sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3−/− or Mlkl−/− mice, respectively) and assessed the roles of necroptosis in AP. We found that Ripk3−/− mice had significantly more severe pancreatic edema and inflammation associated with macrophage and neutrophil infiltration than control mice. Consistently, Mlkl−/− mice were more susceptible to caerulein-induced AP, which occurred in a time- and dose-dependent manner, than control mice. Mlkl−/− mice exhibit weight loss, edematous pancreatitis, necrotizing pancreatitis, and acinar cell dedifferentiation in response to tissue damage. Genetic deletion of Mlkl resulted in downregulation of the antiapoptotic genes Bclxl and Cflar in association with increases in the numbers of apoptotic cells, as detected by TUNEL assay. These findings suggest that RIPK3 and MLKL-mediated necroptosis exerts protective effects in AP and caution against the use of necroptosis inhibitors for AP treatment.

scholarly journals Host Gasdermin D restrains systemic endotoxemia by capturing Proteobacteria in the colon of high-fat diet-feeding mice

Gut Microbes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1946369
Author(s):  
Yujie Shi ◽  
Yixin Zou ◽  
Yonghong Xiong ◽  
Shiyao Zhang ◽  
Mingming Song ◽  
...  
Keyword(s):  
High Fat Diet ◽  
High Fat ◽  
Systemic Endotoxemia

scholarly journals A brief history of studying the role of intestinal factor in aging and/or induction of systemic inflammation: Achievements, challenges, and prospects

2019 ◽  
pp. 4-17
Author(s):  
И.А. Аниховская ◽  
В.А. Белоглазов ◽  
А.И. Гордиенко ◽  
Ю.Д. Иванов ◽  
А.В. Кубышкин ◽  
...  
Keyword(s):  
Life Support ◽  
Age Groups ◽  
World Ocean ◽  
Biological Properties ◽  
Surgical Removal ◽  
Russian Scientist ◽  
Blue Green Algae ◽  
General Pathology ◽  
Systemic Endotoxemia

Изучение кишечного фактора в скорости старения, индукции воспаления и прогрессировании заболеваний неразрывно (прямо или косвенно) связано с великим русским учёным И.И. Мечниковым. Его интуиция инициировала изучение особенностей состава микробиоты долгожителей и операций по удалению толстой кишки (как рудимента и источника токсичных продуктов гниения), результаты которых не имели научного и практического успеха и завершились чуть менее 100 лет тому назад, ознаменовав собой завершение первого этапа исследований. Параллельно с первым стартовал второй этап. Он заключался в изучении биологических свойств и структуры эндотоксина - липополисахарида (ЛПС), число молекул которого на планете очень велико, поскольку ЛПС термостабилен, а главным его источником являются сине-зелёные водоросли, заселившие Мировой океан около 2 миллиардов лет тому назад. Третий этап изучения кишечного фактора в общей патологии стартовал в России треть века назад на стыке первых двух параллельно развивающихся направлений с постулирования системной эндотоксинемии, как облигатного биологического явления и открытия клеточного рецептора TLR4, лигандом которого является ЛПС. В дальнейшем TLR4-подобные рецепторы были обнаружены даже у растений, что позволяет квалифицировать ЛПС не только как экзогормон адаптации, но и как облигатный фактор эволюции. Последняя подразумевает самообновление популяции, для реализации которой облигатные факторы жизнеобеспечения должны обладать и противоположным действием, среди которых стресс и ЛПС. Способность средств снижения содержания ЛПС в крови повышать качество лечебно-профилактического процесса позволяет оптимистично оценивать возможность замедления процессов старения. Первоочередными задачами для достижения поставленной цели являются: определение диапазона физиологических показателей системной эндотоксинемии во всех возрастных группах и создание нового поколения доступных для широкого использования средств селективной элиминации избытка ЛПС из крови (гемодиализ) и кишечника (энтеросорбция), которые могут быть созданы на основе аптамеров. Studying the role of intestinal factor in the rate of aging, induction of inflammation, and progression of diseases is inextricably (directly or indirectly) associated with the great Russian scientist I.I. Mechnikov. His intuition initiated studying the long-livers’ microbiota and the surgical removal of the colon (as a rudiment and source of toxic rotting products), which did not bring any scientific or practical success. These studies were over a little less than 100 years ago marking the end of the first stage of research. The second stage started in parallel with the first one and consisted in studying biological properties and structure of endotoxin (lipopolysaccharide, LPS). LPS molecules are as numerous on the earth as in the air since LPS is thermally stable and generated by blue-green algae that have inhabited the World Ocean two billion years ago. The third stage of studying the intestinal factor in general pathology started in Russia one third of a century ago at the junction of the two above-mentioned, paralleling endeavors - postulating systemic endotoxemia as an obligate biological phenomenon and discovery of the LPS receptor (TLR4) of innate immunity. TLR4 is carried by humans, animals, fish, sponges, and even plants, which suggests that LPS is not only an adaptive exohormone but also an obligate factor of evolution. This implies population self-renewal, which requires that the obligate life-support factors must also possess an opposite effect, including stress and intestinal LPS. The ability of LPS suppressors to enhance the therapeutic and prophylactic process makes promising a possibility of slowing aging. The primary tasks for achieving this goal are determining the range of systemic endotoxemia physiological indexes in all age groups and creating a readily accessible new generation of methods for selective elimination of LPS from blood (hemodialysis) and intestine (enterosorption) that could be developed on the basis of aptamers.

scholarly journals Dynamics of changes in the immune system and antioxidant protection in the treatment of acute pancreatitis

2019 ◽  
Vol 23 (1) ◽  
pp. 110-113
Author(s):  
K. E. Ishcheikin ◽  
V. V. Petrushenko ◽  
D. I. Grebeniuk ◽  
O. M. Zatserkovna ◽  
L. M. Malyk ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Immune System ◽  
Immune Status ◽  
Antioxidant Defense System ◽  
The State ◽  
Control Group ◽  
Comprehensive Treatment ◽  
Antioxidant Protection ◽  
Group I ◽  
Edematous Pancreatitis

The aim of the work was to study the dynamics of changes in the immune system indices and antioxidant protection when fluoroquinolones are included in the treatment regimen for acute edematous pancreatitis. The study included 86 patients with a diagnosis of acute edematous pancreatitis. Group I (n=40) consisted of patients who received treatment according to national and local standards and protocols, group II (n=46) — patients who additionally received fluoroquinolones as part of a comprehensive treatment. The control group consisted of 48 conditionally healthy people in whom laboratory and instrumental diagnostics were carried out similarly to those in patients with acute pancreatitis. According to the purpose and objectives of the study, the state of the immune system and the antioxidant defense system was studied. In patients with acute pancreatitis, changes in the indicators of the immune status were revealed, manifested by the formation of a secondary immunodeficiency with the addition of an autoimmune component. The traditional scheme of pharmacotherapy of acute pancreatitis without the use of antibiotics made it possible to partially correct the indicators of immune status. The use of ciprofloxacin in the complex pharmacotherapy of acute pancreatitis contributed to the normalization of the studied parameters. Thus, the use of fluoroquinolones in the complex pharmacotherapy of acute pancreatitis made it possible to effectively normalize the state of the immune system, cytokine and antioxidant statuses.

scholarly journals Systemic Endotoxin in Peritoneal Dialysis Patients

2018 ◽  
Vol 38 (5) ◽  
pp. 381-384 ◽  
Author(s):  
Ali M. Shendi ◽  
Nathan Davies ◽  
Andrew Davenport
Keyword(s):  
Peritoneal Dialysis ◽  
Extracellular Volume ◽  
Peritoneal Membrane ◽  
Dialysis Patients ◽  
Fungal Cell ◽  
Membrane Function ◽  
Patient Demographics ◽  
Markers Of Inflammation ◽  
Systemic Endotoxemia

Previous reports linked systemic endotoxemia in dialysis patients to increased markers of inflammation, cardiovascular disease, and mortality. Many peritoneal dialysis (PD) patients use acidic, hypertonic dialysates, which could potentially increase gut permeability, resulting in systemic endotoxemia. However, the results from studies measuring endotoxin in PD patients are discordant. We therefore measured systemic endotoxin in 55 PD outpatients attending for routine assessment of peritoneal membrane function; mean age 58.7 ± 16.4 years, 32 (58.2%) male, 21 (38.2%) diabetic, median duration of PD treatment 19.5 (13 – 31) months, 32 (58.2%) using 22.7 g/L dextrose dialysates, and 47 (85.5%) icodextrin. The median systemic endotoxin concentration was 0.0485 (0.0043 – 0.103) Eu/mL. We found no association between endotoxin levels and patient demographics, markers of inflammation, serum albumin, N-terminal pro-brain natriuretic peptide, extracellular volume measured by bioimpedance, blood pressure, PD prescriptions or peritoneal membrane transporter status, or medications. The measurement of endotoxin can be lowered by failure to effectively release protein-bound endotoxin prior to analysis and increased by contamination when taking blood samples and processing and storing the samples. Additionally, contamination with β–glucan from fungal cell walls and the use of different assays to analyze endotoxin can also give differing results. These factors may help to explain the disparate results reported in different studies. Our study would suggest that exposure to standard peritoneal dialysates does not substantially increase systemic endotoxin. However, until endotoxin assays can measure free and bound endotoxin separately, the role of endotoxin causing inflammation in PD patients remains to be determined.

Effect of Propofol and Fentanyl on Brain Oxidative Stress after Systemic Lipopolysaccharide Injection in Rats

2021 ◽  
Vol 11 ◽  
Author(s):  
Omar M.E. Abdel-Salam ◽  
Eman R. Youness ◽  
Nadia A. Mohammed ◽  
Amr M.M. Ibrahim
Keyword(s):  
Oxidative Stress ◽  
Active Form ◽  
Saline Group ◽  
Paraoxonase 1 ◽  
Stress Markers ◽  
Anesthetic Agents ◽  
Systemic Endotoxemia ◽  
Brain Oxidative Stress ◽  
The Brain ◽  
Different Doses

Systemic inflammation causes brain oxidative stress, a prerequisite for neurodegeneration. In this study, we investigated the effect of the anesthetic agents propofol and fentanyl on brain oxidative stress during mild systemic endotoxemia induced by lipopolysaccharide (LPS) endotoxin. For this purpose, rats were administered LPS (400 μg/kg, intraperitoneally; i.p.), treated at the same time with different doses of propofol or fentanyl, i.p., and euthanized 4 h later. Other groups were treated with the saline, only propofol, or only fentanyl. Oxidative stress markers including malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) were determined. In addition, nuclear factor kappaB (NF-kB), paraoxonase-1 (PON-1), and butyrylcholinesterase (BChE) activities were measured in the brain tissue. Results showed that compared with the saline group, administration of LPS caused a marked and significant increase in brain MDA and NO combined with depletion of GSH and decreased PON-1 and BChE activities. Additionally, the active form of NF-kB was significantly increased in the brain of LPS only-treated rats. Treatment with propofol or fentanyl led to a marked and significant decrease in the levels of brain MDA and NO together with a significant increase in GSH and restoration of PON-1 and BChE activities. Furthermore, lower levels of active form of NF-kB were found following treatment with propofol or fentanyl compared with those in the LPS only group. Collectively, these results suggest that propofol and fentanyl exhibit an antioxidant action and attenuate the endotoxin-induced brain oxidative stress.

Interstitial Edematous Pancreatitis

2020 ◽  
Author(s):  
Jahinover Mazo ◽  
Paoulina Ivanova ◽  
Yuliya Mazo ◽  
Zohaib Khan, BSc
Keyword(s):  
Edematous Pancreatitis

scholarly journals Zinc transporter Slc39a14 regulates inflammatory signaling associated with hypertrophic adiposity

2016 ◽  
Vol 310 (4) ◽  
pp. E258-E268 ◽  
Author(s):  
Catalina Troche ◽  
Tolunay Beker Aydemir ◽  
Robert J. Cousins
Keyword(s):  
Adipose Tissue ◽  
Cytokine Production ◽  
Zinc Transporter ◽  
Intracellular Zinc ◽  
Systemic Endotoxemia ◽  
Differentiation Marker ◽  
Plasma Leptin ◽  
Zinc Distribution ◽  
Lower Expression

Zinc is a signaling molecule in numerous metabolic pathways, the coordination of which occurs through activity of zinc transporters. The expression of zinc transporter Zip14 ( Slc39a14), a zinc importer of the solute carrier 39 family, is stimulated under proinflammatory conditions. Adipose tissue upregulates Zip14 during lipopolysaccharide-induced endotoxemia. A null mutation of Zip14 (KO) revealed that phenotypic changes in adipose include increased cytokine production, increased plasma leptin, hypertrophied adipocytes, and dampened insulin signaling. Adipose tissue from KO mice had increased levels of preadipocyte markers, lower expression of the differentiation marker (PPARγ), and activation of NF-κB and STAT3 pathways. Our overall hypothesis was that ZIP14 would play a role in adipocyte differentiation and inflammatory obesity. Global Zip14 KO causes systemic endotoxemia. The observed metabolic changes in adipose metabolism were reversed when oral antibiotics were administrated, indicating that circulating levels of endotoxin were in part responsible for the adipose phenotype. To evaluate a mechanism, 3T3-L1 cells were differentiated into adipocytes and treated with siRNA to knock down Zip14. These cells had an impaired ability to mobilize zinc, which caused dysregulation of inflammatory pathways (JAK2/STAT3 and NF-κB). The Zip14 deletion may limit the availability of intracellular zinc, yielding the unique phenotype of inflammation coupled with hypertrophy. Taken together, these results suggest that aberrant zinc distribution observed with Zip14 ablation impacts adipose cytokine production and metabolism, ultimately increasing fat deposition when exposed to endotoxin. To our knowledge, this is the first investigation into the mechanistic role of ZIP14 in adipose tissue regulation and metabolism.

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