scholarly journals The Role of HSP70 in the Protective Effects of NVP-AUY922 on Multiple Organ Dysfunction Syndrome in Endotoxemic Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Pang-Yen Liu ◽  
Hsin-Hsueh Shen ◽  
Ching-Wen Kung ◽  
Shu-Ying Chen ◽  
Chia-Hsien Lu ◽  
...  
Keyword(s):  
Heat Shock ◽  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Multiple Organ ◽  
High Morbidity ◽  
Protective Effects ◽  
Multiple Organ Dysfunction ◽  
Lps Challenge ◽  
Anti Inflammatory ◽  
Hsp 90

Sepsis is defined as a life-threatening organ dysfunction syndrome with high morbidity and mortality caused by bacterial infection. The major characteristics of sepsis are systemic inflammatory responses accompanied with elevated oxidative stress, leading to multiple organ dysfunction syndrome (MODS), and disseminated intravascular coagulation (DIC). As a molecular chaperon to repair unfolded proteins, heat shock protein 70 (HSP70) maintains cellular homeostasis and shows protective effects on inflammatory damage. HSP 90 inhibitors were reported to exert anti-inflammatory effects via activation of the heat shock factor-1 (HSF-1), leading to induction of HSP70. We evaluated the beneficial effect of HSP 90 inhibitor NVP-AUY 922 (NVP) on multiple organ dysfunction syndrome induced by lipopolysaccharide (LPS) and further explored the underlying mechanism. NVP (5 mg/kg, i.p.) was administered 20 h prior to LPS initiation (LPS 30 mg/kg, i.v. infusion for 4 h) in male Wistar rats. Results demonstrated that pretreatment with NVP significantly increased survival rate and prevented hypotension at 6 h after LPS injection. Plasma levels of ALT, CRE and LDH as well as IL-1β and TNF-α were significantly reduced by NVP at 6 h after LPS challenge. The induction of inducible NO synthase in the liver, lung and heart and NF-κB p-p65 and caspase 3 protein expression in the heart were also attenuated by NVP. In addition, NVP markedly induced HSP70 and HO-1 proteins in the liver, lung and heart after LPS injection. These results indicated that NVP possessed the anti-inflammatory and antioxidant effects on LPS-induced acute inflammation, which might be associated with HSP70 and HO-1, leading to prevent MODS in sepsis. NVP might be considered as a novel therapeutic strategy in the prevention of sepsis-induced MODS.

scholarly journals Characterization and Hepatoprotections of Ganoderma lucidum Polysaccharides against Multiple Organ Dysfunction Syndrome in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yiwen Zhang ◽  
Yanbo Feng ◽  
Wenshuai Wang ◽  
Le Jia ◽  
Jianjun Zhang
Keyword(s):  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Ganoderma Lucidum ◽  
Multiple Organ ◽  
Antioxidant Enzyme Activities ◽  
Inflammatory Factor ◽  
Multiple Organ Dysfunction ◽  
Natural Medicine ◽  
Ganoderma Lucidum Polysaccharides ◽  
Anti Inflammatory

Background. The liver is one of the most commonly affected organs in multiple organ dysfunction syndrome (MODS). In recent years, there have been many studies on Ganoderma lucidum polysaccharides (GLP), but the role of GLP in MODS is still unclear. The purpose of this work was to explore the antioxidant, anti-inflammatory, and protective effects of GLP on the liver in MODS model mice. Methods. The characteristic properties of GLP were processed by physicochemical analysis. The MODS models were successfully established with intraperitoneal injection of zymosan in Kunming strain mice. The antioxidant, anti-inflammatory, and hepatoprotective effects of GLP were processed both in vitro and in vivo by evaluating the oxidative parameters, inflammatory factors, and liver pathological observations. Results. The characterization analysis revealed that GLP was a pyranose mainly composed of glucose with the molecular weights (Mw) of 8309 Da. The experimental results proved that GLP had potential hepatoprotection possibly by improving the antioxidant status (scavenging excessive oxygen radicals, increasing the antioxidant enzyme activities, and reducing the lipid peroxide), alleviating the inflammatory response (reducing the inflammatory factor levels), and guaranteeing the liver functions. Conclusions. This research suggested that GLP had the potential to be developed as a natural medicine for the treatment of multiple organ failure.

scholarly journals Stress and Redox Regulation. Heat shock response in a rat model of septic multiple organ dysfunction syndrome.

1999 ◽  
Vol 114 (5) ◽  
pp. 295-302 ◽  
Author(s):  
Toru TAKAHASHI ◽  
Tsutomu SUZUKI ◽  
Akira YAMASAKI ◽  
Takashi TSUKIJI ◽  
Masahisa HIRAKAWA ◽  
...  
Keyword(s):  
Heat Shock ◽  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Rat Model ◽  
Heat Shock Response ◽  
Redox Regulation ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Shock Response

scholarly journals MORTALITY PREVENTION IN SEPTIC MICE WITH MULTIPLE ORGAN DYSFUNCTION SYNDROME: THE OPTIMAL DOSE OF INTRAPERITONEAL HEAT SHOCK PROTEIN 70

2018 ◽  
Vol 11 (11) ◽  
pp. 183
Author(s):  
Igl Sukamto ◽  
Bambang Purwanto ◽  
Ambar Mudigdo ◽  
Suroto Suroto ◽  
Bhisma Murti ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Effective Dose ◽  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Heat Shock Protein 70 ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Mice Model ◽  
Experimental Group

Objective: Heat shock protein 70 (HSP70) reduces the expression of cytochrome C, B-cell lymphoma-associated X, and cysteine-aspartic acid protease 3 (Caspase 3), in apoptosis of multiple organ dysfunction syndrome (MODS), and thereby can prevent death. Previous researchers used 226 mg/kgBW/intraperitoneal (ip) of HSP70. This study aimed to determine the lowest effective dose of HSP70 to prevent death in sepsis mice model with MODS.Methods: This was a randomized control trial conducted at Pusat Antar Universitas (PAU), Gadjah Mada University, Yogyakarta, Indonesia, from April 1, 2017 to April 21, 2017. The study subjects were Balb/c strain mice. The drug used to induce death was lipopolysaccharides (LPS). The drug used to prevent death in this study was Rat HSP70. A sample of 25 mice was randomized into five groups with each consisting of five mice: (1) Control group with NaCl, (2) experimental group receiving LPS injection of 0.25 mg/kgBW/i.p, (3) experimental group receiving the same dose of LPS injection with HSP70 injection of 100 μg/kgBW/ip, (4) experimental group receiving the same dose of LPS injection with HSP70 injection of 200 μg/kgBW/ip, and (5) experimental group receiving the same dose of LPS injection with HSP70 injection of 300 μg/kgBW/ip. Percentage of live mice between groups was compared by Chi-square test.Results: 3 days after intervention, 13 (86.7%) live mice in the experimental group with ≥100 μg/kgBW/i.p HSP70 were >2 (40%) live mice in the experimental group with <100 μg/kgBW/i.p HSP70, with p=0.038. All mice receiving ≥200 μg/kgBW/ip HSP70 in the experimental group were Alive 3 days after intervention.Conclusion: The lowest effective dose of HSP70 to prevent death in sepsis mice model with MODS is 200 μg/kgBW/ip. All mice are alive 3 days after receiving ≥200 μg/kgBW/ip HSP70. 

Multiple Organ Dysfunction Syndrome of Alcoholic Origin in an 18-Year-Old Patient

2018 ◽  
Vol 2 (12) ◽  
Author(s):  
Francesco Gazia ◽  
Giacomo De Luca ◽  
Imbalzano Gabriele ◽  
Vincenzo Pellicanò
Keyword(s):  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction

IMPACT probability of poor outcome and plasma cytokine concentrations are associated with multiple organ dysfunction syndrome following traumatic brain injury

2019 ◽  
Vol 131 (6) ◽  
pp. 1931-1937 ◽  
Author(s):  
Sungho Lee ◽  
Hyunsoo Hwang ◽  
Jose-Miguel Yamal ◽  
J. Clay Goodman ◽  
Imoigele P. Aisiku ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Sofa Score ◽  
Plasma Concentrations ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Poor Outcome ◽  
Initial Plasma

OBJECTIVETraumatic brain injury (TBI) is a major cause of morbidity and mortality. Multiple organ dysfunction syndrome (MODS) occurs frequently after TBI and independently worsens outcome. The present study aimed to identify potential admission characteristics associated with post-TBI MODS.METHODSThe authors performed a secondary analysis of a recent randomized clinical trial studying the effects of erythropoietin and blood transfusion threshold on neurological recovery after TBI. Admission clinical, demographic, laboratory, and imaging parameters were used in a multivariable Cox regression analysis to identify independent risk factors for MODS following TBI, defined as maximum total Sequential Organ Failure Assessment (SOFA) score > 7 within 10 days of TBI.RESULTSTwo hundred patients were initially recruited and 166 were included in the final analysis. Respiratory dysfunction was the most common nonneurological organ system dysfunction, occurring in 62% of the patients. International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) probability of poor outcome at admission was significantly associated with MODS following TBI (odds ratio [OR] 8.88, 95% confidence interval [CI] 1.94–42.68, p < 0.05). However, more commonly used measures of TBI severity, such as the Glasgow Coma Scale, Injury Severity Scale, and Marshall classification, were not associated with post-TBI MODS. In addition, initial plasma concentrations of interleukin (IL)–6, IL-8, and IL-10 were significantly associated with the development of MODS (OR 1.47, 95% CI 1.20–1.80, p < 0.001 for IL-6; OR 1.26, 95% CI 1.01–1.58, p = 0.042 for IL-8; OR 1.77, 95% CI 1.24–2.53, p = 0.002 for IL-10) as well as individual organ dysfunction (SOFA component score ≥ 1). Finally, MODS following TBI was significantly associated with mortality (OR 5.95, 95% CI 2.18–19.14, p = 0.001), and SOFA score was significantly associated with poor outcome at 6 months (Glasgow Outcome Scale score < 4) when analyzed as a continuous variable (OR 1.21, 95% CI 1.06–1.40, p = 0.006).CONCLUSIONSAdmission IMPACT probability of poor outcome and initial plasma concentrations of IL-6, IL-8, and IL-10 were associated with MODS following TBI.

Sign in / Sign up

Export Citation Format

Share Document