Translational Application of Fluorescent Molecular Probes for the Detection of Reactive Oxygen and Nitrogen Species Associated with Intestinal Reperfusion Injury

Abstract

Acute mesenteric ischemia, caused by an abrupt interruption of blood flow in the mesenteric vessels, is associated with high mortality. When treated with surgical interventions or drugs to re-open the vascular lumen, the reperfusion process itself can inflict damage to the intestinal wall. Ischemia and reperfusion injury comprise complex mechanisms involving disarrangement of the splanchnic microcirculatory flow and impairment of the mitochondrial respiratory chain due to initial hypoxemia and subsequent oxidative stress during the reperfusion phase. This pathophysiologic process results in the production of large amounts of reactive oxygen (ROS) and nitrogen (RNS) species, which damage deoxyribonucleic acid, protein, lipids, and carbohydrates by autophagy, mitoptosis, necrosis, necroptosis, and apoptosis. Fluorescence-based systems using molecular probes have emerged as highly effective tools to monitor the concentrations and locations of these often short-lived ROS and RNS. The timely and accurate detection of both ROS and RNS by such an approach would help to identify early injury events associated with ischemia and reperfusion and increase overall clinical diagnostic sensitivity. This abstract describes the pathophysiology of intestinal ischemia and reperfusion and the early biological laboratory diagnosis using fluorescent molecular probes anticipating clinical decisions in the face of an extremely morbid disease.

Potent Ruthenium–Ferrocene Bimetallic Antitumor Antiangiogenic Agent That Circumvents Platinum Resistance: From Synthesis and Mechanistic Studies to In Vivo Evaluation in Zebrafish

“…We note that despite its widespread use for ROS measurement in cells, H 2 DCF-DA based ROS assay has several limitations . Therefore, we reassessed the ROS generation ability of 1 using dihydroethidium (DHE) and hydroxyphenyl fluorescein (HPF) as alternative and more selective ROS probes . DHE and HPF are known for their ability to selectively detect intracellular O 2 •– and HO • radicals, respectively.…”

“…50 Therefore, we reassessed the ROS generation ability of 1 using dihydroethidium (DHE) and hydroxyphenyl fluorescein (HPF) as alternative and more selective ROS probes. 51 DHE and HPF are known for their ability to selectively detect intracellular O 2…”

Corilagin alleviates intestinal ischemia/reperfusion-induced intestinal and lung injury in mice via inhibiting NLRP3 inflammasome activation and pyroptosis

“…Simultaneously, available oxygen generates oxidative hypoxanthine and superoxide anion radicals (O 2− ) during reperfusion, which are converted to hydrogen peroxide (H 2 O 2 ) and cleaved to hydroxyl radicals (HO − ) ( Bertoni et al, 2018 ). The ROS (O 2− , H 2 O 2 and HO − ) triggers nucleic acid fragmentation and lipid peroxidation, leading to various cellular death and changes in microvascular and mucosal permeability ( Holanda et al, 2021 ). In the current study, Cor significantly inhibited intestinal MDA content and up-regulated SOD activity, and similarly reversed the dysregulation of MDA content, SOD and GSH activities in lung tissue in the II/R mice, which is consistent with previous reports ( Lv et al, 2019 ; Zhang et al, 2019 ).…”

Transplanted hair follicle mesenchymal stem cells alleviated small intestinal ischemia–reperfusion injury via intrinsic and paracrine mechanisms in a rat model

“…Clinically, the treatment of intestinal IR injury consists of supporting symptomatic treatment, maintaining haemodynamic stability, maintaining sufficient oxygen saturation and correcting electrolyte balance disorder ( Gutiérrez-Sánchez et al, 2021 ). Drugs that target the mechanism of IR are still under development and have not been effectively applied in the clinic ( Gonzalez et al, 2015 ; de Holanda et al, 2021 ). As a consequence, it is crucial to find new and effective methods to reduce intestinal IR injury.…”