Dexmedetomidine post‐treatment attenuates cardiac ischaemia/reperfusion injury by inhibiting apoptosis through HIF‐1α signalling

Peng, Ke; Chen, Wei rong; Xia, Fan; Liu, Hong; Meng, Xiao Wen; Zhang, Juan; Liu, Hua Yue; Xia, Zheng; Ji, Fu

doi:10.1111/jcmm.14795

Cited by 36 publications

(35 citation statements)

References 41 publications

(98 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have suggested the neuroprotective effects of DEX in various models. [31][32][33][34] In recent years, researchers found that DEX inhibited lidocaine-induced neurotoxicity. 16,17,23 In this study, we also verified the role of SIRT1/FOXO3a signaling in the effect of DEX on lidocaine-induced neurotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine protects against lidocaine-induced neurotoxicity through SIRT1 downregulation-mediated activation of FOXO3a

Zheng

Guo

et al. 2020

Hum Exp Toxicol

View full text Add to dashboard Cite

Lidocaine, a typical local anesthetic, has been shown to directly induce neurotoxicity in clinical settings. Dexmedetomidine (DEX) is an alpha-2-adrenoreceptor agonist that has been used as anxiolytic, sedative, and analgesic agent which has recently found to protect against lidocaine-induced neurotoxicity. Nicotinamide adenine dinucleotide-dependent deacetylase sirtuin-1 (SIRT1)/forkhead box O3 (FOXO3a) signaling is critical for maintaining neuronal function and regulation of the apoptotic pathway. In the present study, we designed in vitro and in vivo models to investigate the potential effects of lidocaine and DEX on SIRT1 and FOXO3a and to verify whether SIRT1/FOXO3a-mediated regulation of apoptosis is involved in DEX-induced neuroprotective effects against lidocaine. We found that in both PC12 cells and brains of mice, lidocaine decreased SIRT1 level through promoting the degradation of SIRT1 protein. Lidocaine also increased FOXO3a protein level and increased the acetylation of SIRT1 through inhibiting SIRT1. Upregulation of SIRT1 or downregulation of FOXO3a significantly inhibited lidocaine-induced changes in both cell viability and apoptosis. DEX significantly inhibited the lidocaine-induced decrease of SIRT1 protein level and increase of FOXO3a protein level and acetylation of FOXO3a. Downregulation of SIRT1 or upregulation of FOXO3a suppressed DEX-induced neuroprotective effects against lidocaine. The data suggest that SIRT1/FOXO3a is a potential novel target for alleviating lidocaine-induced neurotoxicity and provide more theoretical support for the use of DEX as an effective adjunct to alleviate chronic neurotoxicity induced by lidocaine.

show abstract

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine protects against lidocaine-induced neurotoxicity through SIRT1 downregulation-mediated activation of FOXO3a

Zheng

Guo

et al. 2020

Hum Exp Toxicol

View full text Add to dashboard Cite

show abstract

“…Melatonin also regulates HIF expression (152). HIF-1 modulation plays a crucial role in regulating the apoptotic process (153). Glucose -insulin-potassium (GIK) solution, similar to the one used for adults to metabolically activate the myocardium, has a positive influence on the apoptotic process as well (154).…”

Section: Reducing the Apoptotic Processmentioning

confidence: 99%

Getting an Early Start in Understanding Perinatal Asphyxia Impact on the Cardiovascular System

et al. 2020

View full text Add to dashboard Cite

Perinatal asphyxia (PA) is a burdening pathology with high short-term mortality and severe long-term consequences. Its incidence, reaching as high as 10 cases per 1000 live births in the less developed countries, prompts the need for better awareness and prevention of cases at risk, together with management by easily applicable protocols. PA acts first and foremost on the nervous tissue, but also on the heart, by hypoxia and subsequent ischemia-reperfusion injury. Myocardial development at birth is still incomplete and cannot adequately respond to this aggression. Cardiac dysfunction, including low ventricular output, bradycardia, and pulmonary hypertension, complicates the already compromised circulatory status of the newborn with PA. Multiorgan and especially cardiovascular failure seem to play a crucial role in the secondary phase of hypoxic-ischemic encephalopathy (HIE) and its high mortality rate. Hypothermia is an acceptable solution for HIE, but there is a fragile equilibrium between therapeutic gain and cardiovascular instability. A profound understanding of the underlying mechanisms of the nervous and cardiovascular systems and a close collaboration between the bench and bedside specialists in these domains is compulsory. More resources need to be directed toward the prevention of PA and the consecutive decrease of cardiovascular dysfunction. Not much can be done in case of an unexpected acute event that produces PA, where recognition and prompt delivery are the key factors for a positive clinical result. However, the situation is different for high-risk pregnancies or circumstances that make the fetus more vulnerable to asphyxia. Improving the outcome in these cases is possible through careful monitoring, identifying the high-risk pregnancies, and the implementation of novel prenatal strategies. Also, apart from adequately supporting the heart through the acute episode, there is a need for protocols for long-term cardiovascular follow-up. This will increase our recognition of any lasting myocardial damage and will enhance our perspective on the real impact of PA. The goal of this article is to review data on the cardiovascular consequences of PA, in the context of an immature cardiovascular system, discuss the potential contribution of cardiovascular impairment on short and long-term outcomes, and propose further directions of research in this field.

show abstract

“…Serum samples were collected and frozen at -80°C before assays. A commercial ELISA kit (Life diagnostics, Lincoln, USA) was used as previously described [30]. The absorbance values were measured at 450 nm on a microplate reader.…”

Section: Quantitative Real-time Polymerase Chain Reactionmentioning

confidence: 99%

Heat Shock Protein 70 Protects the Heart from Ischemia/Reperfusion Injury through Inhibition of p38 MAPK Signaling

Song

Meng

et al. 2020

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Background. Heat shock protein 70 (Hsp70) has been shown to exert cardioprotection. Intracellular calcium ([Ca2+]i) overload induced by p38 mitogen-activated protein kinase (p38 MAPK) activation contributes to cardiac ischemia/reperfusion (I/R) injury. However, whether Hsp70 interacts with p38 MAPK signaling is unclear. Therefore, this study investigated the regulation of p38 MAPK by Hsp70 in I/R-induced cardiac injury. Methods. Neonatal rat cardiomyocytes were subjected to oxygen-glucose deprivation for 6 h followed by 2 h reoxygenation (OGD/R), and rats underwent left anterior artery ligation for 30 min followed by 30 min of reperfusion. The p38 MAPK inhibitor (SB203580), Hsp70 inhibitor (Quercetin), and Hsp70 short hairpin RNA (shRNA) were used prior to OGD/R or I/R. Cell viability, lactate dehydrogenase (LDH) release, serum cardiac troponin I (cTnI), [Ca2+]i levels, cell apoptosis, myocardial infarct size, mRNA level of IL-1β and IL-6, and protein expression of Hsp70, phosphorylated p38 MAPK (p-p38 MAPK), sarcoplasmic/endoplasmic reticulum Ca2+-ATPase2 (SERCA2), phosphorylated signal transducer and activator of transcription3 (p-STAT3), and cleaved caspase3 were assessed. Results. Pretreatment with a p38 MAPK inhibitor, SB203580, significantly attenuated OGD/R-induced cell injury or I/R-induced myocardial injury, as evidenced by improved cell viability and lower LDH release, resulted in lower serum cTnI and myocardial infarct size, alleviation of [Ca2+]i overload and cell apoptosis, inhibition of IL-1β and IL-6, and modulation of protein expressions of p-p38 MAPK, SERCA2, p-STAT3, and cleaved-caspase3. Knockdown of Hsp70 by shRNA exacerbated OGD/R-induced cell injury, which was effectively abolished by SB203580. Moreover, inhibition of Hsp70 by quercetin enhanced I/R-induced myocardial injury, while SB203580 pretreatment reversed the harmful effects caused by quercetin. Conclusions. Inhibition of Hsp70 aggravates [Ca2+]i overload, inflammation, and apoptosis through regulating p38 MAPK signaling during cardiac I/R injury, which may help provide novel insight into cardioprotective strategies.

show abstract

Dexmedetomidine post‐treatment attenuates cardiac ischaemia/reperfusion injury by inhibiting apoptosis through HIF‐1α signalling

Cited by 36 publications

References 41 publications

Dexmedetomidine protects against lidocaine-induced neurotoxicity through SIRT1 downregulation-mediated activation of FOXO3a

Dexmedetomidine protects against lidocaine-induced neurotoxicity through SIRT1 downregulation-mediated activation of FOXO3a

Getting an Early Start in Understanding Perinatal Asphyxia Impact on the Cardiovascular System

Heat Shock Protein 70 Protects the Heart from Ischemia/Reperfusion Injury through Inhibition of p38 MAPK Signaling

Contact Info

Product

Resources

About