Ethyl-pyruvate reduces lung injury matrix metalloproteinases and cytokines and improves survival in experimental model of severe acute pancreatitis

Matone, Jacques; Moretti, Ana Iochabel Soares; Apodaca-Torrez, Franz Robert; Goldenberg, Alberto

doi:10.1590/s0102-86502013000800002

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…Administration of EP significantly reduced the lung injury associated with the pancreatitis. Matone et al tested EP and reported similar results to our study in rat lung [38].…”

Section: Discussionsupporting

confidence: 88%

“…In the current study serum IL-6 was measured as a marker of inflammation and a significant improvement in serum IL-6 levels was obtained with the use of EP. The EP has an inhibitory effect on some of the pro-inflammatory cytokines through the inhibition of NF-κβ, and these may have mediated the observed beneficial effects of EP on ANP, as reflected by pancreatic tissue damage and the overall mortality rate [27, 28, 38].…”

Section: Discussionmentioning

confidence: 99%

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Ethyl pyruvate treatment ameliorates pancreatic damage: evidence from a rat model of acute necrotizing pancreatitis

Türkyılmaz

Çekiç

Usta

et al. 2019

aoms

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A b s t r a c tIntroduction: Ethyl pyruvate (EP), a natural flavoring and fragrance agent, has been shown to exert anti-inflammatory and antioxidant actions. We tested the potential beneficial effects of EP in a rat model of acute necrotizing pancreatitis (ANP), a serious condition with a significant inflammatory explosion and oxidative stress. Material and methods: Fifty-two adult male Sprague-Dawley rats were divided into four groups: sham + saline, sham + EP, ANP + saline, and ANP + EP. The ANP was induced by glycodeoxycholic acid and cerulein. Animals were sacrificed at 48 h and biochemical, hematological, and histological markers of ANP and inflammation were assessed. The extent of mortality, systemic cardiorespiratory variables, pancreatic microcirculation, renal/hepatic functions, acinar cell injury and enzyme markers for pancreas and lung tissues were investigated. Results: The EP-treated ANP group presented significantly lower mortality than the untreated ANP group (44% (7/16) vs. 19% (3/16), respectively, p < 0.05). Administration of EP resulted in significantly lower levels of IL-6 (ANP + saline: 5470 ±280 vs. ANP + EP: 2250 ±180 pg/ml, p < 0.05). Compared with the ANP group, the ANP + EP group had a lower pancreatic necrosis score (1.45 ±0.2 vs. 0.96 ±0.2, p < 0.05). Moreover, intraperitoneal EP administration had a positive effect on most indices of pancreatitis (amylase and alanine transaminase levels) and lung damage (except lung malondialdehyde levels) as they decreased towards baseline values. Conclusions:The results from this experimental study indicate that EP, a nontoxic chemical approved by the Food and Drug Administration as a food additive, provides positive effects on the course of pancreatitis, suggesting potential usefulness in management of ANP.

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“…Administration of EP significantly reduced the lung injury associated with the pancreatitis. Matone et al tested EP and reported similar results to our study in rat lung [38].…”

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Ethyl pyruvate treatment ameliorates pancreatic damage: evidence from a rat model of acute necrotizing pancreatitis

Türkyılmaz

Çekiç

Usta

et al. 2019

aoms

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“…This theory is supported by the following evidence in which the alveolar-capillary barrier is severely injured and the pulmonary permeability is significantly increased in an experimental acute necrotizing pancreatitis [6]. The anti-inflammatory agent EP (40 mg/kg intraperitoneally injected every 6 h for 48 h) markedly decreases the lung permeability and alleviates pulmonary edema at least partly by reducing pulmonary inflammation and neutrophils infiltration in a couple of experimental SAP models with acute lung injury [6, 10, 52, 53]. Increased local and systemic levels of IL-6 are associated with inflammatory process, including neutrophil infiltration of the alveolar space, resulting in lung injury [54].…”

Section: The Effect Of Ep On Acute Lung Injuriesmentioning

confidence: 99%

Ethyl pyruvate is a novel anti-inflammatory agent to treat multiple inflammatory organ injuries

2016

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Ethyl pyruvate (EP) is a simple derivative of pyruvic acid, which is an important endogenous metabolite that can scavenge reactive oxygen species (ROS). Treatment with EP is able to ameliorate systemic inflammation and multiple organ dysfunctions in multiple animal models, such as acute pancreatitis, alcoholic liver injury, acute respiratory distress syndrome (ARDS), acute viral myocarditis, acute kidney injury and sepsis. Recent studies have demonstrated that prolonged treatment with EP can ameliorate experimental ulcerative colitis and slow multiple tumor growth. It has become evident that EP has pharmacological anti-inflammatory effect to inhibit multiple early inflammatory cytokines and the late inflammatory cytokine HMGB1 release, and the anti-tumor activity is likely associated with its anti-inflammatory effect. EP has been tested in human volunteers and in a clinical trial of patients undergoing cardiac surgery in USA and shown to be safe at clinical relevant doses, even though EP fails to improve outcome of the heart surgery, EP is still a promising agent to treat patients with multiple inflammatory organ injuries and the other clinical trials are on the way. This review focuses on how EP is able to ameliorate multiple organ injuries and summarize recently published EP investigations. Graphical AbstractThe targets of the anti-inflammatory agent EP

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“…Pulmonary arterial pressure (PAP) and systemic pressure were measured as described previously. 15 In brief, two catheters were inserted into the main pulmonary artery and the right common carotid artery under fluoroscopic guidance to measure PAP (including diastolic PAP, systolic PAP, and mean PAP) and mean systemic arterial pressure, respectively. The two catheters were linked to a transducer, and the pressure was simultaneously recorded on a multichannel physiologic recorder (PowerLab 8/30; AD Instruments Pty Ltd, Sydney, Australia).…”

Section: Measurement Of Hemodynamic Parametersmentioning

confidence: 99%

“…Treatment with EP has been shown to improve survival or ameliorate organ dysfunction in a wide variety of preclinical models, including models of severe sepsis, acute lung injury, and acute pancreatitis. [13][14][15] Considering the pathophysiology of PAH and the roles of HMGB1 and ROS in the progression of this disease, it is reasonable to hypothesize that inhibition of HMGB1 and ROS might prevent the development of PAH. Indeed, our previous study showed that intraperitoneal injection of EP could attenuate monocrotaline-induced PAH and reverse pulmonary vascular remodeling in rats by inhibiting the release of TNFα and IL-6 and reducing the expression of ET1.…”

Section: Introductionmentioning

confidence: 99%

Intratracheal instillation of ethyl pyruvate nanoparticles prevents the development of shunt-flow-induced pulmonary arterial hypertension in a rat model

Li¹,

Zhang²,

Cao³

et al. 2016

IJN

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Purpose:To investigate whether inhalation of ethyl pyruvate (EP) encapsulated with poly(ethylene glycol)-block-lactide/glycolide copolymer nanoparticles (EP-NPs) can prevent the development of shunt-flow-induced hyperkinetic pulmonary arterial hypertension (PAH) in a rat model. Materials and methods: Rats were separated into five groups: blank (ie, no treatment after shunt flow), normal control (ie, no shunt flow or treatment), EP-NP instillation, EP-only instillation, and vehicle. The animals received intratracheal instillation of EP-NPs or other treatments immediately after a shunt flow, and treatment continued weekly until the end of the experiment. Hemodynamic data were recorded, pulmonary arterial remodeling was assessed, and levels of inflammatory mediators and ET1 expression in the lung and serum were analyzed. In addition, retention of EP in the lungs of rats in the EP-NP and EP-only groups was measured using highperformance liquid chromatography. Results: After 12 weeks, hemodynamic abnormalities and pulmonary arterial remodeling were improved in the EP-NP instillation group, compared with the blank, EP-only, and vehicle groups (P,0.05). In addition, the EP-NP group showed significantly decreased levels of HMGB1, IL-6, TNFα, reactive oxygen species, and ET1 in the lung during PAH development (P,0.05). Furthermore, EP-NP instillation was associated with reduced serum levels of inflammatory factors and ET1. High-performance liquid-chromatography measurement indicated that EP retention was greater in the lungs of the EP-NP group than in the EP-only group. Conclusion: EP-NP instillation attenuated inflammation and prevented pulmonary arterial remodeling during the development of PAH induced by shunt flow. In the future, EP-NP delivery into the lung might provide a novel approach for preventing PAH.

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Ethyl-pyruvate reduces lung injury matrix metalloproteinases and cytokines and improves survival in experimental model of severe acute pancreatitis

Abstract: The ethyl-pyruvate diminishes acute lung injury inflammatory response in acute pancreatitis and ameliorates survival when compared to control group, in the experimental model of necrotizing acute pancreatitis.

Cited by 7 publications

References 21 publications

Ethyl pyruvate treatment ameliorates pancreatic damage: evidence from a rat model of acute necrotizing pancreatitis

Ethyl pyruvate treatment ameliorates pancreatic damage: evidence from a rat model of acute necrotizing pancreatitis

Ethyl pyruvate is a novel anti-inflammatory agent to treat multiple inflammatory organ injuries

Intratracheal instillation of ethyl pyruvate nanoparticles prevents the development of shunt-flow-induced pulmonary arterial hypertension in a rat model

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