Metabolomic profiling to characterize acute intestinal ischemia/reperfusion injury

Khadaroo, Rachel G.; Churchill, Thomas A.; Tso, Victor; Madsen, Karen; Lukowski, Chris M.; Salim, Saad Y.

doi:10.1371/journal.pone.0179326

Cited by 14 publications

(12 citation statements)

References 49 publications

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“…The first study regarding ischemia–reperfusion and the role of NETs, Oklu et al . established an IR model on the unilateral hind limb of mice and demonstrated the possible involvement of NETs in myofiber injury [ 90 ]. Inspiration from this finding inspired later investigators to focus on IR in other organs.…”

Section: Nets and Intestinal Inflammationmentioning

confidence: 99%

The emerging role of neutrophilic extracellular traps in intestinal disease

et al. 2022

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Neutrophil extracellular traps (NETs) are extracellular reticular fibrillar structures composed of DNA, histones, granulins and cytoplasmic proteins that are delivered externally by neutrophils in response to stimulation with various types of microorganisms, cytokines and host molecules, etc. NET formation has been extensively demonstrated to trap, immobilize, inactivate and kill invading microorganisms and acts as a form of innate response against pathogenic invasion. However, NETs are a double-edged sword. In the event of imbalance between NET formation and clearance, excessive NETs not only directly inflict tissue lesions, but also recruit pro-inflammatory cells or proteins that promote the release of inflammatory factors and magnify the inflammatory response further, driving the progression of many human diseases. The deleterious effects of excessive release of NETs on gut diseases are particularly crucial as NETs are more likely to be disrupted by neutrophils infiltrating the intestinal epithelium during intestinal disorders, leading to intestinal injury, and in addition, NETs and their relevant molecules are capable of directly triggering the death of intestinal epithelial cells. Within this context, a large number of NETs have been reported in several intestinal diseases, including intestinal infections, inflammatory bowel disease, intestinal ischemia–reperfusion injury, sepsis, necrotizing enterocolitis, and colorectal cancer. Therefore, the formation of NET would have to be strictly monitored to prevent their mediated tissue damage. In this review, we summarize the latest knowledge on the formation mechanisms of NETs and their pathophysiological roles in a variety of intestinal diseases, with the aim of providing an essential directional guidance and theoretical basis for clinical interventions in the exploration of mechanisms underlying NETs and targeted therapies.

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Section: Nets and Intestinal Inflammationmentioning

confidence: 99%

The emerging role of neutrophilic extracellular traps in intestinal disease

et al. 2022

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“…Small intestinal ischemia/reperfusion (IIR) injury is a common and serious pathological condition that occurs during numerous clinical events, including superior mesenteric artery (SMA) occlusion, liver transplantation and hemorrhagic shock (1). Furthermore, IIR injury may lead to severe damage to remote organs, including the lungs, kidneys and liver, thereby adversely affecting the prognosis of patients (2,3).…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rb1 attenuates intestinal ischemia/reperfusion‑induced inflammation and oxidative stress via activation of the PI3K/Akt/Nrf2 signaling pathway

Chen

Wang

et al. 2019

Mol Med Report

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Ginsenoside Rb1 (GRb1), one of the major active saponins isolated from ginseng, has recently been reported to protect various organs against ischemia/reperfusion (IR) injury; however, the mechanisms underlying these protective effects following intestinal IR (IIR) remain unclear. The present study aimed to evaluate the effects of GRb1 on IIR injury and determine the mechanisms involved in these effects. Sprague Dawley rats were subjected to 75 min of superior mesenteric artery occlusion, followed by 3 h of reperfusion. GRb1 (15 mg/kg) was administered intraperitoneally 1 h prior to the induction of IIR, with or without intravenous administration of Wortmannin [WM; a phosphoinositide 3-kinase (PI3K) inhibitor, 0.6 mg/kg]. The degree of intestinal injury and oxidative stress-induced damage was determined by histopathologic evaluation and measurement of the serum activity levels of D-lactate, diamine oxidase and endotoxin, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and 8-iso-prostaglandin F 2α (8-iso-PGF 2α ). The protein expression levels of p85, phosphorylated (p)-p85, protein kinase B (Akt), p-Akt and nuclear factor erythroid 2-related factor 2 (Nrf2) were determined via western blotting, and the concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 were measured via ELISA. It was revealed that IIR led to severe intestinal injury (as determined by significant increases in intestinal Chiu scores), which was accompanied with disruptions in the integrity of the intestinal mucosal barrier. IIR also increased the expression levels of TNF-α, IL-1β, IL-6, MDA and 8-iso-PGF 2α in the intestine, and decreased those of SOD. GRb1 reduced intestinal histological injury, and suppressed inflammatory responses and oxidative stress. Additionally, the protective effects of GRb1 were eliminated by WM. These findings indicated that GRb1 may ameliorate IIR injury by activating the PI3K/protein kinase B/Nrf2 pathway.

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“…Two different concentrations of I-FABP were chosen to spike the urine samples, 2 and 5 ng/mL. It has been previously determined that 2.7 ng/mL or higher would be the critical concentration of the I-FABP that, if found in the patient urine, would require immediate surgical intervention . Therefore, we selected these two values as representative for the critical range of I-FABP concentrations.…”

Section: Resultsmentioning

confidence: 99%

Non-invasive Point-of-Care Device To Diagnose Acute Mesenteric Ischemia

et al. 2018

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Inadequate blood supply to the intestine can lead to acute mesenteric ischemia (AMI), with a mortality rate ranging from 60% to 90%. This high mortality rate is partially due to late detection and the lack of efficient early diagnostic tests. There is an urgent need for a point-of-care tool for immediate bedside diagnosis. Here we present for the first time a rapid and non-invasive electrochemical biosensor device based on nonfaradic impedance spectroscopy to detect intestinal fatty-acid binding protein (I-FABP) as an indication of AMI. The electrochemical biosensors consist of gold interdigitated electrodes that were fabricated using photolithographic techniques on top of silicon dioxide substrates. The electrode surfaces were functionalized with an I-FABP capture antibody (CAnB) to entice the target protein, while gold nanoparticles (GNPs) functionalized with detection antibodies (DAnB-GNPs) were utilized as a novel mechanism to enhance the detection signal. Quantification of the I-FABP concentration in the medium depended on its attachment to CAnB and DAnB-GNPs in a sandwich manner, where the latter boosts the impedance signal through its binding to the I-FABP. This non-invasive non-faradic electric biosensor device demonstrates the potential for bench-to-bedside translation with the goal of decreasing morbidity and mortality from AMI.

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Metabolomic profiling to characterize acute intestinal ischemia/reperfusion injury

Cited by 14 publications

References 49 publications

The emerging role of neutrophilic extracellular traps in intestinal disease

The emerging role of neutrophilic extracellular traps in intestinal disease

Ginsenoside Rb1 attenuates intestinal ischemia/reperfusion‑induced inflammation and oxidative stress via activation of the PI3K/Akt/Nrf2 signaling pathway

Non-invasive Point-of-Care Device To Diagnose Acute Mesenteric Ischemia

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