Study of Cardioprotective Effects of Necroptosis Inhibitors on Isolated Rat Heart Subjected to Global Ischemia–Reperfusion

Dmitriev, Yu. V.; Минасян, С. М.; Демченко, Е. А.; Galagudza, M. M.

doi:10.1007/s10517-013-2124-2

Cited by 44 publications

(31 citation statements)

References 5 publications

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“…1A, B). These effects of Nec-1, which can be attributed in part to the working myocardium, are consistent with a study of Dmitriev et al (2013), who have shown a marked initial elevation of systolic intraventricular pressure. In contrast to our findings, diastolic BP after intracoronary Nec-1 application was unchanged (Dmitriev et al 2013).…”

supporting

confidence: 91%

“…However, it should be pointed out that in spite of this increase in HR, no ventricular tachycardia nor fibrillation was recorded at any of timepoints of the protocol. Although there were several protocol differences in comparison to ours (the used dose, application into the femoral vein vs. intracoronary application), Dmitriev et al (2013) have also shown HR values being unchanged at 10 min after Nec-1 administration. On the other hand, as they have monitored heart function only during a short 10-min stabilization period prior to ischemia/reperfusion, it cannot be ruled out that heart rate was also changed at a later timepoint after the drug administration like seen in our hands.…”

contrasting

confidence: 70%

“…Although Nec-1 and Nec-1i have been widely used to examine necroptosis in myocardial pathologies (Oerlemans et al 2012, Koudstaal et al 2015, Dmitriev et al 2013, Miyamae et al 2014) effects of these agents on basal function of the cardiovascular system have not been investigated so far. In this study conducted in healthy rats, delta sBP recorded at 30 min after the drug administration did not differ among the groups.…”

mentioning

confidence: 99%

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Effects of Necrostatin-1, an Inhibitor of Necroptosis, and its Inactive Analogue Nec-1i on Basal Cardiovascular Function

Szobi¹,

Rajtík²,

Adameová

2016

Physiol Res

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Inhibitionof receptor-interacting serine/threonine-protein kinase 1 (RIP1) by necrostatin-1 (Nec-1) alleviates cardiac injury due to prevention of necroptotic cell death. Its inactive analogue necrostatin-1i (Nec-1i), lacking RIP1 activity, serves as a suitable control. It is unknown if these agents influence the heart function in the absence of damaging stimuli. For this purpose, we measured intraarterial blood pressure (systolic -sBP and diastolic -dBP) and ECG parameters after a bolus administration of Nec-1 and Nec-1i in rats during 30 min. Nec-1, unlike Nec-1i, increased sBP and dBP, as well as heart rate reaching the peak at 20 min. The P wave duration tended to be decreased and the duration of the PR interval was shortened by Nec-1 indicating faster conduction of the impulses through atria to the ventricles.The drugs did not influence the QTc interval duration and no episode of ventricular arrhythmia was observed. In summary, Nec-1 temporarily modulates blood pressure and electrical function of the healthy heart. These effects of Nec-1 are likely due to its off-target action or RIP1 has an important role in the regulation of cardiovascular function independently of its action on the necroptotic pathway.

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supporting

confidence: 91%

contrasting

confidence: 70%

mentioning

confidence: 99%

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Effects of Necrostatin-1, an Inhibitor of Necroptosis, and its Inactive Analogue Nec-1i on Basal Cardiovascular Function

Szobi¹,

Rajtík²,

Adameová

2016

Physiol Res

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“…90 This was supported by later findings of a protective effect of Nec-1 in a myocardial IRI model. [91][92][93] Additionally, Nec-1 plus zVAD-fmk double blockade 94 or vanadyl sulfate (perhaps via induction of FLIP 95 ) were found to be beneficial. However, genetic evidence for a role for necroptosis has been largely limited to effects of RIPK3 deficiency in some models.…”

Section: Ischemia-reperfusion Injury and Necrostatinsmentioning

confidence: 94%

“…Upon discovery of regulated necrosis, necroptosis was suggested as being involved. [91][92][93] Additionally, Nec-1 plus zVAD-fmk double blockade 94 or vanadyl sulfate (perhaps via induction of FLIP 95 ) were found to be beneficial. [91][92][93] Additionally, Nec-1 plus zVAD-fmk double blockade 94 or vanadyl sulfate (perhaps via induction of FLIP 95 ) were found to be beneficial.…”

Section: Ischemia-reperfusion Injury and Necrostatinsmentioning

confidence: 95%

The in vivo evidence for regulated necrosis

Tonnus

Linkermann

2017

Immunological Reviews

103

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Necrosis is a hallmark of several widespread diseases or their direct complications. In the past decade, we learned that necrosis can be a regulated process that is potentially druggable. RIPK3- and MLKL-mediated necroptosis represents by far the best studied pathway of regulated necrosis. During necroptosis, the release of damage-associated molecular patterns (DAMPs) drives a phenomenon referred to as necroinflammation, a common consequence of necrosis. However, most studies of regulated necrosis investigated cell lines in vitro in a cell autonomous manner, which represents a non-physiological situation. Conclusions based on such work might not necessarily be transferrable to disease states in which synchronized, non-cell autonomous effects occur. Here, we summarize the current knowledge of the pathophysiological relevance of necroptosis in vivo, and in light of this understanding, we reassess the morphological classification of necrosis that is generally used by pathologists. Along these lines, we discuss the paucity of data implicating necroptosis in human disease. Finally, the in vivo relevance of non-necroptotic forms of necrosis, such as ferroptosis, is addressed.

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The role of necroptosis in disease and treatment

Liu

Xie

Ren

et al. 2021

MedComm

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Necroptosis, a distinctive type of programmed cell death different from apoptosis or necrosis, triggered by a series of death receptors such as tumor necrosis factor receptor 1 (TNFR1), TNFR2, and Fas. In case that apoptosis process is blocked, necroptosis pathway is initiated with the activation of three key downstream mediators which are receptor‐interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain‐like protein (MLKL). The whole process eventually leads to destruction of the cell membrane integrity, swelling of organelles, and severe inflammation. Over the past decade, necroptosis has been found widely involved in life process of human beings and animals. In this review, we attempt to explore the therapeutic prospects of necroptosis regulators by describing its molecular mechanism and the role it played in pathological condition and tissue homeostasis, and to summarize the research and clinical applications of corresponding regulators including small molecule inhibitors, chemicals, Chinese herbal extracts, and biological agents in the treatment of various diseases.

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Study of Cardioprotective Effects of Necroptosis Inhibitors on Isolated Rat Heart Subjected to Global Ischemia–Reperfusion

Cited by 44 publications

References 5 publications

Effects of Necrostatin-1, an Inhibitor of Necroptosis, and its Inactive Analogue Nec-1i on Basal Cardiovascular Function

Effects of Necrostatin-1, an Inhibitor of Necroptosis, and its Inactive Analogue Nec-1i on Basal Cardiovascular Function

The in vivo evidence for regulated necrosis

The role of necroptosis in disease and treatment

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