Oxidative Stress Evaluation in Ischemia Reperfusion Models: Characteristics, Limits and Perspectives

Abstract

Ischemia reperfusion injury is a complex process consisting of a seemingly chaotic but actually organized and compartmentalized shutdown of cell function, of which oxidative stress is a key component. Studying oxidative stress, which results in an imbalance between reactive oxygen species (ROS) production and antioxidant defense activity, is a multi-faceted issue, particularly considering the double function of ROS, assuming roles as physiological intracellular signals and as mediators of cellular component damage. Herein, we propose a comprehensive overview of the tools available to explore oxidative stress, particularly in the study of ischemia reperfusion. Applying chemistry as well as biology, we present the different models currently developed to study oxidative stress, spanning the vitro and the silico, discussing the advantages and the drawbacks of each set-up, including the issues relating to the use of in vitro hypoxia as a surrogate for ischemia. Having identified the limitations of historical models, we shall study new paradigms, including the use of stem cell-derived organoids, as a bridge between the in vitro and the in vivo comprising 3D intercellular interactions in vivo and versatile pathway investigations in vitro. We shall conclude this review by distancing ourselves from “wet” biology and reviewing the in silico, computer-based, mathematical modeling, and numerical simulation options: (a) molecular modeling with quantum chemistry and molecular dynamic algorithms, which facilitates the study of molecule-to-molecule interactions, and the integration of a compound in a dynamic environment (the plasma membrane...); (b) integrative systemic models, which can include many facets of complex mechanisms such as oxidative stress or ischemia reperfusion and help to formulate integrated predictions and to enhance understanding of dynamic interaction between pathways.

Biomarkers and Utility of the Antioxidant Potential of Probiotic Lactobacilli and Bifidobacteria as Representatives of the Human Gut Microbiota

“…Reperfusion induces tissue reactions that fuel the production of ROS, sequestration of proinflammatory immunocytes in ischemic tissues, endoplasmic reticulum stress, and the development of postischemic capillary "no-reflow", which exacerbate tissue damage. Thus, OS is one of the most important pathological mechanisms of reperfusion injury, which causes apoptosis, autophagy, inflammation, and other tissue damage in several ways, ultimately causing irreversible damage to organs [8][9][10]. Ischemic/reperfusion injury is the most common cause of disease and death, and is a widespread problem in organ transplantation [11,12].…”

Protective effect of fluoxetine against oxidative stress induced by renal ischemia-reperfusion injury via the regulation of miR-450b-5p/Nrf2 axis

“…Numerous studies have suggested that oxidative stress could be regulated by multiple molecular mechanisms [18][19][20]. Oxygen supply to renal IRI leads to the formation of ROS and inflammatory response, and the overproduction of ROS is considered possible causes of renal IRI [21,22].…”

Oxidative Injury in Ischemic Stroke: A Focus on NADPH Oxidase 4

“…TIA has no infarcts, while RIND, stroke in evolution, and completed stroke have varying cerebral infarcts. Neurons lose their ability to maintain normal transmembrane ionic gradients after ischemia [ 50 ] and then cause a series of pathological changes, such as oxidative stress [ 51 ], excitotoxicity, inflammation [ 52 ], and apoptosis [ 53 ]. Increased ROS triggers oxidative stress after ischemia-reperfusion and then aggravates blood-brain barrier injury.…”