Nonenzymatic lipid mediators, neuroprostanes, exert the antiarrhythmic properties of docosahexaenoic acid

Roy, Jérôme; Oger, Camille; Thireau, Jérôme; Roussel, Julien; Mercier-Touzet, Olivia; Faure, Delinger; Pinot, Edith; Farah, Charlotte; Taber, Douglass F.; Cristol, Jean‐Paul; Lee, Jetty Chung‐Yung; Lacampagne, Alain; Galano, Jean‐Marie; Durand, Thierry; Guennec, Jean‐Yves Le

doi:10.1016/j.freeradbiomed.2015.04.014

Cited by 60 publications

(64 citation statements)

References 62 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The acute effects of LYC were studied at 0.14 nM, 1.4 nM and 14 nM on single cardiomyocytes obtained from Ctrl animals. In each mouse, the heart was rapidly excised after euthanasia (cervical dislocation) and submitted to enzymatic action (liberase) using a Langendorff perfusion system in order to disperse single rod-shaped left ventricular (LV) myocytes161758. Only cardiomyocytes with clear edges were used within 1–6 h of isolation.…”

Section: Methodsmentioning

confidence: 99%

“…Contractility and intracellular free Ca 2+ were measured in single LV myocytes field-stimulated at 1.0 Hz with 1-ms current pulses to assess cell shortening and Ca 2+ transients, respectively, as described16173858. Briefly, cardiomyocytes were bathed in a physiological solution (in mM: 117 NaCl, 5.7 KCl, 4.4 NaHCO 3 , 1.5 KH 2 PO 4 , 1.7 MgCl 2 , 21 HEPES, 1.8 CaCl 2 and 11 glucose).…”

Section: Methodsmentioning

confidence: 99%

“…Myocytes were field-stimulated at 1 Hz with 1-ms current pulses delivered via two platinum electrodes, one on each side of the perfusion chamber. During the rest period that followed stimulation, myocytes were repetitively scanned along their entire length at 1.5-ms intervals, for a maximum of 6 s175859. The intensity of the laser was reduced to 5% of maximum to decrease cell damage and dye bleaching.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Biodegradable Polymeric Nanocapsules Prevent Cardiotoxicity of Anti-Trypanosomal Lychnopholide

Branquinho

Roy

Farah

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Chagas disease is a neglected parasitic disease caused by the protozoan Trypanosoma cruzi. New antitrypanosomal options are desirable to prevent complications, including a high rate of cardiomyopathy. Recently, a natural substance, lychnopholide, has shown therapeutic potential, especially when encapsulated in biodegradable polymeric nanocapsules. However, little is known regarding possible adverse effects of lychnopholide. Here we show that repeated-dose intravenous administration of free lychnopholide (2.0 mg/kg/day) for 20 days caused cardiopathy and mortality in healthy C57BL/6 mice. Echocardiography revealed concentric left ventricular hypertrophy with preserved ejection fraction, diastolic dysfunction and chamber dilatation at end-stage. Single cardiomyocytes presented altered contractility and Ca2+ handling, with spontaneous Ca2+ waves in diastole. Acute in vitro lychnopholide application on cardiomyocytes from healthy mice also induced Ca2+ handling alterations with abnormal RyR2-mediated diastolic Ca2+ release. Strikingly, the encapsulation of lychnopholide prevented the cardiac alterations induced in vivo by the free form repeated doses. Nanocapsules alone had no adverse cardiac effects. Altogether, our data establish lychnopholide presented in nanocapsule form more firmly as a promising new drug candidate to cure Chagas disease with minimal cardiotoxicity. Our study also highlights the potential of nanotechnology not only to improve the efficacy of a drug but also to protect against its adverse effects.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Biodegradable Polymeric Nanocapsules Prevent Cardiotoxicity of Anti-Trypanosomal Lychnopholide

Branquinho

Roy

Farah

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, Roy et al , showed that the oxidation of ω‐3 PUFAs by ROS releases 4( RS )‐4‐F 4t ‐NeuroP from docosahexaenoic acid, which is necessary to prevent isoproterenol‐induced arrhythmias in mice with myocardial infarction (173), prevent early arrhythmias in rats after an ischemia/reperfusion period (174), or prevent breast cancer proliferation (175). As previously observed in different oxidative conditions (176), the researchers proposed that in oxidative stress conditions, such as ischemic events, 4( RS )‐4‐F 4t ‐NeuroP is responsible for the antiarrhythmic properties of ω‐3 PUFAs by countering the cellular stress by ROS.…”

Section: Physiological Implications Of Rosmentioning

confidence: 99%

Physiological role of reactive oxygen species as promoters of natural defenses

et al. 2017

Self Cite

View full text Add to dashboard Cite

It has been 60 yr since the discovery of reactive oxygen species (ROS) in biology and the beginning of the scientific community's attempt to understand the impact of the unpaired electron of ROS molecules in biological pathways, which was eventually noted to be toxic. Several studies have shown that the presence of ROS is essential in triggering or acting as a secondary factor for numerous pathologies, including metabolic and genetic diseases; however, it was demonstrated that chronic treatment with antioxidants failed to show efficacy and positive effects in the prevention of diseases or health complications that result from oxidative stress. On the contrary, such treatment has been shown to sometimes even worsen the disease. Because of the permanent presence of ROS in organisms, elaborate mechanisms to adapt with these reactive molecules and to use them without necessarily blocking or preventing their actions have been studied. There is now a large body of evidence that shows that living organisms have conformed to the presence of ROS and, in retrospect, have adapted to the bioactive molecules that are generated by ROS on proteins, lipids, and DNA. In addition, ROS have undergone a shift from being molecules that invoked oxidative damage in regulating signaling pathways that impinged on normal physiological and redox responses. Working in this direction, this review unlocks a new conception about the involvement of cellular oxidants in the maintenance of redox homeostasis in redox regulation of normal physiological functions, and an explanation for its essential role in numerous pathophysiological states is noted.-Roy, J., Galano, J.-M., Durand, T., Le Guennec, J.-Y., Lee, J. C.-Y. Physiological role of reactive oxygen species as promoters of natural defenses.

show abstract

“…9), showed potent D118, page 7 of 10 dose-dependent AAP in cellulo and also in vivo in PMI mice. At the cellular level, the mechanism of action is unlikely to be due to a β-blocker effect, but the AAP can instead be explained by a rycal-like effect; in particular, stabilization of the RyR2 complex with FKBP12.6 (Andersson and Marks, 2010;Roy, 2015).…”

Section: Neuroprostanesmentioning

confidence: 99%

Non enzymatic metabolites of polyunsaturated fatty acids: friend or foe

Bultel-Poncé¹,

Guy²,

Oger³

et al. 2015

OCL

Self Cite

View full text Add to dashboard Cite

-Under condition of oxidative stress, free radical mediated peroxidation of polyunsaturated fatty acids generates in vivo, cyclic metabolites like the isoprostanes, neuroprostanes, dihomo-isoprostanes, isofuranes among a large number of key products which participate in many pathophysiological processes. These metabolites display a wide range of biological actions, and some of them are now the most reliable indicators of oxidative stress in humans. In this review, we will discuss several key points of our understanding of those cyclic polyunsaturated fatty acids derivatives, going from multi-step syntheses, analytical chemistry and biological activities.Keywords: biomarkers / polyunsaturated fatty acid / radical peroxidation / isoprostanes / neuroprostanes / isofurans / total synthesis Résumé -La peroxydation radicalaire des acides gras polyinsaturés, constituants majeurs des membranes cellulaires, conduit à de nombreux métabolites, comme les isoprostanes, les neuroprostanes, les dihomo-isoprostanes, les isofuranes. Certaines isoprostanes sont à présent des marqueurs du stress oxydant cellulaire les plus significatifs utilisés en clinique. Ces lipides oxygénés possèdent également un large spectre d'activités biologiques. Cette revue fera le point sur notre dernière stratégie de synthèse organique multi-étapes pour obtenir ces molécules pures et sur des résultats récents issus de collaborations avec des collègues biologistes et cliniciens.

show abstract

Nonenzymatic lipid mediators, neuroprostanes, exert the antiarrhythmic properties of docosahexaenoic acid

Cited by 60 publications

References 62 publications

Biodegradable Polymeric Nanocapsules Prevent Cardiotoxicity of Anti-Trypanosomal Lychnopholide

Biodegradable Polymeric Nanocapsules Prevent Cardiotoxicity of Anti-Trypanosomal Lychnopholide

Physiological role of reactive oxygen species as promoters of natural defenses

Non enzymatic metabolites of polyunsaturated fatty acids: friend or foe

Contact Info

Product

Resources

About