Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury

Todorović, Zoran; Đurašević, Siniša; Stojković, Maja; Grigorov, Ilijana; Pavlović, Slađan; Jasnić, Nebojša; Tosti, Tomislav; Macut, Jelica Bjekić; Thiemermann, Christoph; Đorđević, Jelena

doi:10.3390/ijms22062798

Cited by 11 publications

(4 citation statements)

References 107 publications

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“…Lipids are important building blocks of the body and serve various functions (Natesan & Kim, 2021). Particularly, tissue ischemia causes anaerobic circumstances in which enzymes are inactivated, and reperfusion can cause oxidative stress, which causes detrimental changes in membrane lipids, the creation of aldehydes, and chain destruction till cell death (Todorović et al, 2021). The undesired build‐up of fatty acids (FA) that leads to lipotoxicity is the essential event in such a cascade of damaging events in the cell.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine attenuates myocardial ischemia–reperfusion injury in hyperlipidemic rats by inhibiting inflammation, oxidative stress and NF‐κB

Gao,

Du,

et al. 2023

Chem Biol Drug Des

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The present study was conducted to determine the protective effect of Dexmedetomidine (DEX) in myocardial ischemia–reperfusion injury in hyperlipidemic rats. Towards this, the effect of DEX was first evaluated on the infarct size and the histopathology of cardiac tissues using TTC and H and E staining, and it was found that DEX significantly improved the infarct size and architecture of the myocardial tissues following the I/R injury. DEX also showed significant improvement in various examined hemodynamic parameters (e.g., LVSP, and ± dp/dtmax) in a dose‐dependent manner. The lipid profile (LDL, VLDL, TC, TG, and HDL level) of the rats were also found significantly improved in DEX‐treated rats. The level of various pro‐inflammatory cytokines (IL‐1β, IL‐6, IL‐10, IL‐17, and TNF‐α), cardiac injury (CK, CK‐MB, Troponin I AST, ALT, and LDH), and oxidative stress (MDA, SOD, and GSH) biomarkers were also found to be restored near to the normal in DEX‐treated group. It has been found that DEX also significantly reduces apoptosis of rat cardiomyocytes. In western blot analysis, DEX showed a significant reduction in the activation of NF‐κB. In conclusion, our study demonstrated the protective effect of Dexmedetomidine in myocardial ischemia–reperfusion injury in hyperlipidemic rats possibly via amelioration of oxidative stress, and inflammation apoptosis.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine attenuates myocardial ischemia–reperfusion injury in hyperlipidemic rats by inhibiting inflammation, oxidative stress and NF‐κB

Gao,

Du,

et al. 2023

Chem Biol Drug Des

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“…A lipidomic analysis by Todorović et al emphasized the importance of reducing FA overload to mitigate IRI (Todorović et al, 2021). Meldonium, a cardioprotective drug, prevents excessive accumulation of toxic long‐chain FAs in the mitochondria and protects against ROS production (Dambrova et al, 2016; Speijer et al, 2014).…”

Section: Lipis Droplets In Transplantationmentioning

confidence: 99%

Lipid droplets, autophagy, and ER stress as key (survival) pathways during ischemia‐reperfusion of transplanted grafts

Kamińska,

Skrzycki

2024

Cell Biology International

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Ischemia‐reperfusion injury is an event concerning any organ under a procedure of transplantation. The early result of ischemia is hypoxia, which causes malfunction of mitochondria and decrease in cellular ATP. This leads to disruption of cellular metabolism. Reperfusion also results in cell damage due to reoxygenation and increased production of reactive oxygen species, and later by induced inflammation. In damaged and hypoxic cells, the endoplasmic reticulum (ER) stress pathway is activated by increased amount of damaged or misfolded proteins, accumulation of free fatty acids and other lipids due to inability of their oxidation (lipotoxicity). ER stress is an adaptive response and a survival pathway, however, its prolonged activity eventually lead to induction of apoptosis. Sustaining cell functionality in stress conditions is a great challenge for transplant surgeons as it is crucial for maintaining a desired level of graft vitality. Pathways counteracting negative consequences of ischemia‐reperfusion are autophagy and lipid droplets (LD) metabolism. Autophagy remove damaged organelles and molecules driving them to lysosomes, digested simpler compounds are energy source for the cell. Mitophagy and ER‐phagy results in improvement of cell energetic balance and alleviation of ER stress. This is important in sustaining metabolic homeostasis and thus cell survival. LD metabolism is connected with autophagy as LD are degraded by lipophagy, a source of free fatty acids and glycerol—thus autophagy and LD can readily remove lipotoxic compounds in the cell. In conclusion, monitoring and pharmaceutic regulation of those pathways during transplantation procedure might result in increased/improved vitality of transplanted organ.

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“…к минимуму образование пероксинитритов, которые ухудшают эндотелиальную дисфункцию [60]. Мельдоний может нивелировать последствия нежелательного накопления жирных кислот в клетке (что приводит к формированию эффекта липотоксичности), снижая маркеры апоптоза и некроза и повышая антиоксидантную защиту [61], являясь наднозологическим препаратом [62] в борьбе с липотоксичностью [63].…”

Section: коморбидный пациентunclassified

Possibilities of drug correction of the state of the main arteries and microcirculation in patients with chronic heart failure and chronic obstructive pulmonary disease

2022

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Introduction. Patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are increasingly found in the clinical practice. The comorbidity of CHF and COPD promotes high mortality in such patients. Therapy that is prescribed to patients with CHF and COPD may not always have a positive effect on the condition of blood vessels. In this regard, researchers began to pay attention to drugs that have a beneficial effect on blood vessels, without worsening the course of CHF and COPD, one of which is meldonium.The purpose of the study. To study the effect of meldonium as part of complex therapy on arterial stiffness and microcirculation in patients with CHF and COPD.Materials and methods. The open randomized study included 60 patients with CHF IIA stage, II–III functional class (clinical recommendations of RKO, OSSN 2020) and COPD of the I–III degree of airflow restriction (classification GОLD 2021) without exacerbation. The patients were divided into 2 groups: the 1st group – the main group (n = 30) with CHF and COPD, which was prescribed meldonium as part of complex therapy at a dosage of 1000 mg/day, the 2nd group – the control group (n = 30) was on therapy only with basic drugs of CHF and COPD. The observation period is 12 weeks.Results. As a result of 12 weeks of therapy with the inclusion of meldonium in the complex therapy of patients with CHF and COPD, a decrease in the stiffness of the main arteries, an improvement in the regulation and parameters of microcirculation, an increase in the frequency of occurrence of the normocirculatory type of microcirculation were noted.Conclusions. A significant useful effect of complex therapy with the inclusion of meldonium on the condition of arterial stiffness and microcirculation in patients with CHF and COPD has been established, which makes it possible to recommend the use of meldonium in this category of patients.

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Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury

Cited by 11 publications

References 107 publications

Dexmedetomidine attenuates myocardial ischemia–reperfusion injury in hyperlipidemic rats by inhibiting inflammation, oxidative stress and NF‐κB

Dexmedetomidine attenuates myocardial ischemia–reperfusion injury in hyperlipidemic rats by inhibiting inflammation, oxidative stress and NF‐κB

Lipid droplets, autophagy, and ER stress as key (survival) pathways during ischemia‐reperfusion of transplanted grafts

Possibilities of drug correction of the state of the main arteries and microcirculation in patients with chronic heart failure and chronic obstructive pulmonary disease

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