L-Carnitine Reduces Myocardial Oxidative Stress and Alleviates Myocardial Ischemia-Reperfusion Injury by Activating Nuclear Transcription-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) Signaling Pathway

Zhao, Tana; Chen, Shangjun; BingXin, Wang; Cai, Ding

doi:10.12659/msm.923251

Cited by 17 publications

(10 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, in acute conditions, such as in myocardial infarction, LC could mitigate abnormal oxidative stress condition and enhance cardiomyocytes survival. Animal studies and preliminary clinical studies seem to confirm this hypothesis [195][196][197][198]. It is important to note that these first trials suggest that LC improves antioxidative cellular defense, in particular the NRF2 pathway [198].…”

Section: From Caloric Restriction To Cr-related Nutrients: L-carnitinementioning

confidence: 78%

Diabetes Mellitus and Cardiovascular Diseases: Nutraceutical Interventions Related to Caloric Restriction

Senesi

Ferrulli

Luzi

et al. 2021

IJMS

View full text Add to dashboard Cite

Type 2 diabetes (T2DM) and cardiovascular disease (CVD) are closely associated and represent a key public health problem worldwide. An excess of adipose tissue, NAFLD, and gut dysbiosis establish a vicious circle that leads to chronic inflammation and oxidative stress. Caloric restriction (CR) is the most promising nutritional approach capable of improving cardiometabolic health. However, adherence to CR represents a barrier to patients and is the primary cause of therapeutic failure. To overcome this problem, many different nutraceutical strategies have been designed. Based on several data that have shown that CR action is mediated by AMPK/SIRT1 activation, several nutraceutical compounds capable of activating AMPK/SIRT1 signaling have been identified. In this review, we summarize recent data on the possible role of berberine, resveratrol, quercetin, and L-carnitine as CR-related nutrients. Additionally, we discuss the limitations related to the use of these nutrients in the management of T2DM and CVD.

show abstract

Section: From Caloric Restriction To Cr-related Nutrients: L-carnitinementioning

confidence: 78%

Diabetes Mellitus and Cardiovascular Diseases: Nutraceutical Interventions Related to Caloric Restriction

Senesi

Ferrulli

Luzi

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Research has confirmed that Nrf2 protect cardiomyocytes from oxidative stress by increasing detoxification pathways, enhancing antioxidant potential and alleviating oxidative damage in various disease states (20).…”

Section: Ros-associated Mechanism Of Different Concentrations Of Pinacidil Postconditioning In the Rat Cardiac Nrf2-are Signaling Pathwaymentioning

confidence: 99%

ROS‑associated mechanism of different concentrations of pinacidil postconditioning in the rat cardiac Nrf2‑ARE signaling pathway

et al. 2021

View full text Add to dashboard Cite

Previous studies have confirmed that 50 µmol/l pinacidil postconditioning (PPC) activates the nuclear factor-E2 related factor 2 (Nrf2)-antioxidant responsive element (ARE) pathway, which protects the myocardium from ischemia-reperfusion (IR) injury; however, whether this is associated with reactive oxygen species (ROS) generation remains unclear. In the present study, a Langendorff rat model of isolated myocardial IR was established to investigate the mechanism of PPC at different concentrations, as well as the association between the rat myocardial Nrf2-ARE signaling pathway and ROS. A total of 48 rats were randomly divided into the following six groups (n=8 per group): i) Normal; ii) IR iii) 10 µmol/l PPC (P10); iv) 30 µmol/l PPC (P30); v) 50 µmol/l PPC (P50); and vi) N-(2-mercaptopropionyl)-glycine (MPG; a ROS scavenger) + 50 µmol/l pinacidil (P50 + MPG). At the end of reperfusion (T3), compared with the IR group, the P10, P30 and P50 groups exhibited improved cardiac function, such as left ventricular development pressure, heart rate, left ventricular end-diastolic pressure, +dp/dtmax, myocardial cell ultrastructure and mitochondrial Flameng score. Furthermore, the P10 and P50 groups demonstrated the weakest and most marked improvements, respectively. Additionally, in the P10, P30 and P50 groups, the residual ROS content at the end of reperfusion was highly negatively correlated with relative expression levels of Nrf2 gene and protein. Higher pinacidil concentration was associated with higher ROS generation at 5 min post-reperfusion (T2), although this was significantly lower compared with the IR group, as well as with increased expression levels of antioxidant proteins and phase II detoxification enzymes downstream of the Nrf2 and Nrf2-ARE pathways. This result was associated with a stronger ability to scavenge ROS during reperfusion, leading to lower levels of ROS at the end of reperfusion (T3) and less myocardial damage. The optimal myocardial protective effect was achieved by 50 mmol/l pinacidil. However, cardiac function of the P50 + MPG group was significantly decreased, ultrastructure of cardiomyocytes was significantly impaired and the relative expression levels of genes and proteins in the Nrf2-ARE pathway were decreased. The aforementioned results confirmed that different PPC concentrations promoted early generation of ROS and activated the Nrf2-ARE signaling pathway following reperfusion, regulated expression levels of downstream antioxidant proteins and alleviated myocardial IR injury in rats. Treatment with 50 mmol/l pinacidil resulted in the best myocardial protection.

show abstract

“…A variety of other substances have been shown to exert their cardioprotective effects against myocardial I/R injury via HO-1 activation. L-carnitine, either injected intraperitoneally to rats undergoing left anterior descending (LAD) coronary artery occlusion or administered to H9c2 cardiomyoblasts exposed to hypoxia/reoxygenation, reduced oxidative stress and apoptosis likely via activation of Nrf2/HO-1 pathway [ 99 ]. Galanthamine, an alkaloid with anti-inflammatory properties, has been shown to reduce myocardial I/R injury, endoplasmic reticulum stress-related apoptosis, and myocardial fibrosis in rats via activating 5′ adenosine monophosphate-activated protein kinase (AMPK)/Nrf2/HO-1 pathway [ 100 ].…”

Section: Heme Oxygenase System In I/r Injury and Cytoprotectionmentioning

confidence: 99%

The Molecular Mechanisms of Iron Metabolism and Its Role in Cardiac Dysfunction and Cardioprotection

Ravingerová

Kindernay

Barteková

et al. 2020

IJMS

111

View full text Add to dashboard Cite

Iron is an essential mineral participating in different functions of the organism under physiological conditions. Numerous biological processes, such as oxygen and lipid metabolism, protein production, cellular respiration, and DNA synthesis, require the presence of iron, and mitochondria play an important role in the processes of iron metabolism. In addition to its physiological role, iron may be also involved in the adaptive processes of myocardial “conditioning”. On the other hand, disorders of iron metabolism are involved in the pathological mechanisms of the most common human diseases and include a wide range of them, such as type 2 diabetes, obesity, and non-alcoholic fatty liver disease, and accelerate the development of atherosclerosis. Furthermore, iron also exerts potentially deleterious effects that may be manifested under conditions of ischemia/reperfusion (I/R) injury, myocardial infarction, heart failure, coronary artery angioplasty, or heart transplantation, due to its involvement in reactive oxygen species (ROS) production. Moreover, iron has been recently described to participate in the mechanisms of iron-dependent cell death defined as “ferroptosis”. Ferroptosis is a form of regulated cell death that is distinct from apoptosis, necroptosis, and other types of cell death. Ferroptosis has been shown to be associated with I/R injury and several other cardiac diseases as a significant form of cell death in cardiomyocytes. In this review, we will discuss the role of iron in cardiovascular diseases, especially in myocardial I/R injury, and protective mechanisms stimulated by different forms of “conditioning” with a special emphasis on the novel targets for cardioprotection.

show abstract

L-Carnitine Reduces Myocardial Oxidative Stress and Alleviates Myocardial Ischemia-Reperfusion Injury by Activating Nuclear Transcription-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) Signaling Pathway

Cited by 17 publications

References 24 publications

Diabetes Mellitus and Cardiovascular Diseases: Nutraceutical Interventions Related to Caloric Restriction

Diabetes Mellitus and Cardiovascular Diseases: Nutraceutical Interventions Related to Caloric Restriction

ROS‑associated mechanism of different concentrations of pinacidil postconditioning in the rat cardiac Nrf2‑ARE signaling pathway

The Molecular Mechanisms of Iron Metabolism and Its Role in Cardiac Dysfunction and Cardioprotection

Contact Info

Product

Resources

About