Beneficial Effects of Benznidazole during an Infectious-based Situation of Systemic Inflammatory Response: Cecal Ligation and Puncture

Sepsis is characterized by a severe inflammatory response to infection. It remains a major cause of morbidity and mortality in critically ill patients despite developments in monitoring devices, diagnostic tools, and new therapeutic options. Recently, some studies have found that molecular hydrogen is a new therapeutic gas. Our studies have found that hydrogen gas can improve the survival and organ damage in mice and rats with cecal ligation and puncture, zymosan, and lipopolysaccharide-induced sepsis. The mechanisms are associated with the regulation of oxidative stress, inflammatory response, and apoptosis, which might be through NF-κB and Nrf2/HO-1 signaling pathway. In this paper, we summarized the progress of hydrogen treatment in sepsis.

Download Full-text

COMPARISON OF THE MORTALITY AND INFLAMMATORY RESPONSE OF TWO MODELS OF SEPSIS: LIPOPOLYSACCHARIDE VS. CECAL LIGATION AND PUNCTURE

Shock ◽

10.1097/00024382-200013020-00004 ◽

2000 ◽

Vol 13 (2) ◽

pp. 110-116 ◽

Cited By ~ 342

Author(s):

Daniel G. Remick ◽

David E. Newcomb ◽

Gerald L. Bolgos ◽

Douglas R. Call

Keyword(s):

Inflammatory Response ◽

Cecal Ligation ◽

Cecal Ligation And Puncture

Download Full-text

Hemodynamic evaluation of chemical mediators of sepsis during systemic inflammatory response in an experimental animal model

10.1101/2021.09.24.461714 ◽

2021 ◽

Author(s):

GUILHERME DE SOUZA VIEIRA ◽

Fernanda Antunes ◽

Josias Alves Machado ◽

Isabella Cristina Morales ◽

Priscilla Olivieri Benck de Jesus ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Inflammatory Response ◽

Arterial Blood Pressure ◽

Cecal Ligation ◽

Systemic Inflammatory Response ◽

Arterial Blood ◽

Time Period ◽

Sepsis Induction ◽

Surgical Manipulation

The early diagnosis of sepsis increases the chances of its successful treatment. Biomarkers are able to distinguish between systemic inflammatory response syndrome and sepsis and are used to monitor pro- and anti-inflammatory changes associated with the host response to pathogens. A total of 11 rats underwent sepsis induction and measured systolic, diastolic and mean arterial blood pressure. Leukocyte counts, procalcitonin, and nitric oxide also were measured 0, 2, and 4 hours after the induction of sepsis using the cecal ligation and puncture method. The animals were divided into two groups: control (SHAM) and induced. Procalcitonin levels remained within the normal range for an inflammatory response throughout the experiment. There was a statistically insignificant increase in nitric oxide levels. All animals showed increased diastolic arterial blood pressure; however, the increase in the induced animals was even more pronounced. Procalcitonin and nitric oxide levels can increase due to surgical manipulation, while arterial blood pressure was not a good predictor for the onset of sepsis during the time period studied here.

Download Full-text

Systemic Inflammatory Response and Severe Thrombocytopenia after Endovascular Thoracic Aortic Aneurysm Repair

Case Reports in Medicine ◽

10.1155/2017/3018919 ◽

2017 ◽

Vol 2017 ◽

pp. 1-4

Author(s):

Valentina Silvestrin ◽

Stefano Bonvini ◽

Michele Antonello ◽

Franco Grego ◽

Roberto Vettor ◽

...

Keyword(s):

Aortic Aneurysm ◽

Inflammatory Response ◽

Endovascular Repair ◽

Thoracic Aortic Aneurysm ◽

Systemic Inflammatory Response ◽

Aortic Aneurysms ◽

Severe Thrombocytopenia ◽

Laboratory Findings ◽

Thoracic Aortic Aneurysms ◽

Beneficial Effects

After Endovascular repair of thoracic aortic aneurysm, a systemic inflammatory response, named postimplantation syndrome, can develop. This syndrome is characterized by fever, leukocytosis, and elevated CRP plasma levels and its pathogenetic mechanisms are still unknown. Although this syndrome generally resolves within few days, some patients develop a persisting severe inflammatory reaction leading to mild or severe complications. Here we describe the case of a male patient who developed postimplantation inflammatory syndrome and severe thrombocytopenia after endovascular repair of thoracic aortic aneurysm. Treatment with prednisone (50 mg/bid) for two weeks did not improve the clinical and laboratory findings. We utilized danazol, a weak androgen that has been shown to be effective in the treatment of immune and idiopathic thrombocytopenic purpura, and after 12 days of treatment with danazol (200 mg/bid), the patient improved progressively and platelet number increased up to 53,000/μL. Patients undergoing endovascular repair of thoracic aortic aneurysm should be carefully monitored for the development of postimplantation syndrome. This clinical condition is relatively common after the endovascular repair of aortic aneurysm but is rarely observed after endovascular repair of thoracic aortic aneurysms. The different known therapeutical approaches are still empiric, with reported beneficial effects with the use of NSAID, corticosteroids, and danazol.

Download Full-text

Inhibition of Gamma Interferon Decreases Bacterial Load in Peritonitis by Accelerating Peritoneal Fibrin Deposition and Tissue Repair

Infection and Immunity ◽

10.1128/iai.71.5.2766-2774.2003 ◽

2003 ◽

Vol 71 (5) ◽

pp. 2766-2774 ◽

Cited By ~ 14

Author(s):

Gang Qiu ◽

Elizabeth Gribbin ◽

Kathryn Harrison ◽

Neil Sinha ◽

Kingsley Yin

Keyword(s):

Inflammatory Response ◽

Tissue Repair ◽

Bowel Perforation ◽

Bacterial Load ◽

Cecal Ligation ◽

Gamma Interferon ◽

Systemic Inflammatory Response ◽

Fibrin Deposition ◽

Septic Peritonitis ◽

Ifn Γ

ABSTRACT Bowel perforation can lead to significant bacterial spillage, which may then cause septic peritonitis, characterized by a systemic inflammatory response and organ dysfunction. There are several reports that have shown that the development of peritoneal adhesions is dependent on inflammatory cytokine levels and that these adhesions can reduce bacterial spread, possibly by sealing off the cecum in the cecal ligation and puncture (CLP) model of septic peritonitis. There have not, however, been any studies that have utilized a strategy to accelerate tissue repair in order to seal off the injured cecum and reduce bacterial spread as well as ameliorate systemic inflammation. In the present study, we demonstrate that the administration of anti-gamma interferon (IFN-γ) antibody (1.2 mg/kg of body weight, intravenously) accelerated tissue repair via increased fibrin deposition 12 and 24 h after CLP in rats. This increase in fibrin deposition was associated with peritoneal adhesion 24 h after CLP and a reduction in bacterial load compared to the bacterial load of rats given irrelevant antibody. Plasma fibrin levels, however, were not altered after IFN-γ antibody administration, suggesting that the inhibition of IFN-γ activity specifically increased fibrin deposition to the site of injury. Furthermore, plasma interleukin-6, used as a marker of systemic inflammatory response, was reduced in CLP rats given IFN-γ antibody compared to that found in those given irrelevant antibody. These results suggest that the early inhibition of IFN-γ activity in the CLP model is beneficial by accelerating fibrin deposition in cecal tissue to prevent bacterial spread and reduce the systemic inflammatory response. Importantly, increased fibrin deposition in the ceca was not associated with increased plasma fibrin whereas the latter may have detrimental effects associated with coagulation disorders.

Download Full-text

Protein from Hevea brasiliensis “Hev b 13” latex attenuates systemic inflammatory response and lung lesions in rats with sepsis

Brazilian Journal of Biology ◽

10.1590/1519-6984.06316 ◽

2017 ◽

Vol 78 (2) ◽

pp. 271-280 ◽

Cited By ~ 3

Author(s):

L. A. Araújo ◽

P. R. Melo-Reis ◽

F. Mrue ◽

C. M. Gomes ◽

M. A. P. Oliveira ◽

...

Keyword(s):

Inflammatory Response ◽

Hevea Brasiliensis ◽

Rubber Tree ◽

Cecal Ligation ◽

Neutrophil Infiltration ◽

Multiple Organ ◽

Systemic Inflammatory Response ◽

Lung Lesions ◽

Male Wistar Rats ◽

Anti Inflammatory

Abstract Sepsis induces a severe systemic inflammatory response that may result in multiple organ dysfunction and death. Studies using a protein derived from natural Hevea brasiliensis (rubber tree) latex, denominated Hev b 13, have demonstrated important anti-inflammatory effects, but no data have been published regarding its effects on sepsis. The aim of this study was to investigate the effects of Hev b 13 on the inflammatory response and lung lesions of septal rats. Male Wistar rats were submitted to cecal ligation and puncture (CLP), randomized into groups and treated with subcutaneously administered doses of 0.5/2.0/3.0 mg/Kg of Hev b 13. Next, animals were subdivided into three different points in time (1, 6 and 24 hours after treatments) for collection of blood samples and euthanasia accompanied by organ removal. Total and differential leukocyte counts, cytokine dosage and histological assessment were analyzed. Treatment with Hev b 13 resulted in a significant decline in total and differential leukocytes as well as suppression of TNF-α and IL-6 production, associated with the increase in IL-10 and IL-4 in plasma and lung tissue. Moreover, it reduced morphological and pathological changes found in the lungs, including neutrophil infiltration, edema and alveolar thickening. The present study concluded that Hev b 13 exerts anti-inflammatory effects and attenuates lung lesions in septal rats, showing potential for clinical application.

Download Full-text

Methotrexate Ameliorates Systemic Inflammation and Septic Associated-Lung Damage in a Cecal Ligation and Puncture Septic Rat Model

International Journal of Molecular Sciences ◽

10.3390/ijms22179612 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9612

Author(s):

Josep Bringué ◽

Raquel Guillamat-Prats ◽

Maria Luisa Martinez ◽

Eva Torrents ◽

Marta Camprubí-Rimblas ◽

...

Keyword(s):

Inflammatory Response ◽

Low Dose ◽

Cecal Ligation ◽

Inflammatory Cells ◽

Lung Damage ◽

Source Control ◽

Beneficial Effects ◽

Group A ◽

Cecal Ligation Puncture ◽

Host Inflammatory Response

Background: Sepsis is a serious, heterogeneous clinical entity produced by a severe and systemic host inflammatory response to infection. Methotrexate (MTX) is a folate-antagonist that induces the generation of adenosine and also inhibits JAK/STAT pathway; MTX it is widely used as an anti-inflammatory drug to control the immune system. Objective: The aim of this study was to assess the beneficial effects of a single and low dose of MTX in the systemic response and acute lung injury (ALI) induced by sepsis. As in the clinics, we treated our animals with antibiotics and fluids and performed the source control to mimic the current clinic treatment. Methods and main results: Sepsis was induced in rats by a cecal ligation puncture (CLP) procedure. Six hours after induction of sepsis, we proceeded to the source control; fluids and antibiotics were administered at 6 h and 24 h after CLP. MTX (2.5 mg/Kg) was administered 6 h after the first surgery in one CLP experimental group and to one Sham group. A protective effect of MTX was observed through a significant reduction of pro-inflammatory cytokines and a decrease infiltration of inflammatory cells in the lung. In addition, we found a regulation in adenosine receptor A2aR and the metalloproteinases by MTX. Conclusion: A single, low dose of MTX attenuates sepsis lung-associated damage by decreasing pro-inflammatory response, infiltration of pro-inflammatory cells and avoiding defective tissue lung remodeling.

Download Full-text

MEF2C alleviates acute lung injury in cecal ligation and puncture (CLP)-induced sepsis rats by up-regulating AQP1

Allergologia et Immunopathologia ◽

10.15586/aei.v49i5.477 ◽

2021 ◽

Vol 49 (5) ◽

pp. 117-124

Author(s):

Wenmei Liang ◽

Li Guo ◽

Tonghua Liu ◽

Song Qin

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Response ◽

Cecal Ligation ◽

Weight Ratio ◽

Dry Weight ◽

Tunel Staining ◽

Cecal Ligation And Puncture ◽

Tnf Α ◽

Factor Α

Background: Sepsis is a systemic inflammatory response syndrome and leads to patient’s death. Objective: To investigate the effect of myocyte enhancer factor 2 (MEF2C) on acute lung injury (ALI) with sepsis and its possible mechanism.Material and Methods: The cecal ligation and puncture (CLP)-induced sepsis rat model was established. The lung injury was determined by lung wet–dry weight ratio, the concentration of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), Interlukin (IL)-6, IL-1β, and IL-10, were measured by the enzyme-linked-immunosorbent serologic assay kit. The cell apoptosis was detected by TUNEL staining assay.Results: Interestingly, MEF2C was down-regulated in this model. Moreover, adeno-associated virus (AAV)-MEF2C treatment markedly suppressed TNF-α, IL-1β, and IL-6 concentrations but promoted IL-10 concentration in serum in CLP-challenged rats. Besides, overexpression of MEF2C alleviates CLP-induced lung injury. Interestingly, AAV-MEF2C treatment was confirmed to suppress apoptosis in CLP-induced sepsis rats as well as promote aquaporin APQ1 expres-sion. Mechanistically, the rescue experiments indicated that MEF2C alleviated CLP-induced lung inflammatory response and apoptosis via up-regulating AQP1.Conclusion: In summary, overexpression of MEF2C suppressed CLP-induced lung inflamma-tory response and apoptosis via up-regulating AQP1, providing a novel therapeutic target for sepsis-induced ALI.

Download Full-text