Cytotoxicity of propofol in human induced pluripotent stem cell-derived cardiomyocytes

Kido, Koji; Ito, Hiroyuki; Yamamoto, Youichi; Makita, Koshi; Uchida, Tatsuo

doi:10.1007/s00540-017-2441-0

Cited by 16 publications

(11 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, these disruptions caused by cisplatin can be improved by TMZ and CoQ10, suggesting that TMZ and CoQ10 may inhibit cell apoptosis partially through suppressing cisplatin-induced mitochondrial dysfunction. Other studies have also reported the positive modulation of TMZ and CoQ10 on mitochondrial function in damaged cardiomyocytes (35,36), similar to the results of our study.…”

Section: Discussionsupporting

confidence: 93%

Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction

Zhao

2019

Anatol J Cardiol

View full text Add to dashboard Cite

Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction Objective: The objective of this study was to investigate the effects of trimetazidine (TMZ) and coenzyme Q10 (CoQ10) on cisplatin-induced cardiotoxicity in rat cardiomyocytes. Methods: Rat cardiomyocytes were isolated and subjected to cisplatin (200 μM) treatment with and without TMZ (200 μM) and CoQ10 (200 mg/L) pretreatment. The cell viability, apoptosis, oxidant and antioxidant indicators, and mitochondrial dysfunction were examined. Results: TMZ or CoQ10 significantly attenuated cisplatin-induced cell viability inhibition (p<0.01) and apoptosis (p<0.001), and the combined use of TMZ and CoQ10 pretreatment exerted a pronounced effect compared to the effects of using each of these agents individually (p<0.05). TMZ or CoQ10 inhibited the levels of reactive oxidative species (ROS, p<0.01) and malondialdehyde (MDA, p<0.001 and p<0.01, respectively), elevated the activities of antioxidant enzymes superoxide dismutase (SOD, p<0.01) and catalase (CAT, p<0.01 and p<0.05, respectively), evidently enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2, p<0.05), alleviated mitochondrial membrane potential (ΔΨm) loss (p<0.05), and down-regulated the release of cytochrome c (cyto-c) into the cytosol (p<0.01) in cisplatin-treated cells. The combined use of TMZ and CoQ10 treatment was more effective than using either agent alone (p<0.01 for ROS, MDA, CAT, and cytosolic cyto-c; p<0.05 for SOD, nuclear Nrf2, and ΔΨm loss). Conclusion: TMZ and CoQ10 showed protective effects against cisplatin-induced cardiotoxicity via attenuating oxidative stress.

show abstract

Section: Discussionsupporting

confidence: 93%

Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction

Zhao

2019

Anatol J Cardiol

View full text Add to dashboard Cite

show abstract

“…The current study demonstrated the cytotoxicity of propofol and lipid reagents toward muscle cells using a basic, relatively simple experiment, involving murine cell lines. Our results are in accordance with previous studies related to PRIS due to propofol-induced muscle cell injury (7, 25-27). Furthermore, our experiments used differentiated muscle cells derived from murine myoblast cells, which are similarly susceptible to cell damage as pediatric tissues.…”

Section: Discussionsupporting

confidence: 93%

“…Thus a basic and simple experimental model is needed to investigate the detailed mechanism of its occurrence and possible treatments. Hence, experiments using cultured cells have been reported in recent years (25, 26).…”

Section: Discussionmentioning

confidence: 99%

The Basic Study of the Mechanism of Propofol-Related Infusion Syndrome Using a Murine Skeletal Muscle Injury Model

et al. 2019

View full text Add to dashboard Cite

Background The pathophysiological mechanism of propofol-related infusion syndrome (PRIS) is believed to be due to the injury to the mitochondrial electron transport chain and the resultant metabolic disorders that are caused by both propofol agents and the lipid solvent. However, the mechanisms and causative factors of PRIS have not been fully elucidated. Objectives The aim of this study was to evaluate the possibility of a research model using the culture of differentiated C2C12 cells for fundamental research of PRIS. Methods First, differentiated C2C12 cells were cultured accompanied by several concentrations of chemical reagents of 2,6-diisopropylphenol (2,6 DIP) or dimethyl sulfoxide (DMSO) for 60 hours and the cell death rate was examined by trypan blue staining. Second, The cells were incubated with a commercially available propofol reagent or lipid reagent for 48 hours. The supernatant fluid of the cell culture medium was gathered and the numbers of floating cells were measured by cell counter. To investigate the mitochondrial disorder by the propofol preparation, JC-1, an experiment using fluorescent reagent, was performed for the 48 hours with 100 µg/mL propofol incubation. Results The rate of cell death was increased with elevating concentrations both of chemical reagents of 2,6 DIP group and dimethyl sulfoxide group. The rates of cell death were significantly higher in the 2,6 DIP group than DMSO group. The numbers of floating cells were increased with elevating concentrations both commercially available propofol reagent and lipid reagent groups. The decreased red/green fluorescence ratio by JC-1 staining in the propofol 100µg/mL group proved an attenuated mitochondrial membrane potential. Conclusions The dose-dependent cell damage induced by the propofol reagents and a lipid solvent may provide a proposed model as a basic experimental model for further investigations into PRIS.

show abstract

“…Propofol‐induced mitochondrial dysfunction has been proposed as a key mechanism. Kido, Ito, Yamamoto, Makita, and Uchida (2018) treated iPSC‐CMs with different propofol concentrations (0–50 μg·ml −1 ) for 48 hours and measured mitochondrial function. At concentrations above 10 μg·ml −1 , propofol caused mitochondrial dysfunction while higher concentrations induced apoptosis.…”

Section: Using Ipsc Technology To Evaluate Anaesthetic Agents In Cardmentioning

confidence: 99%

“…Reprogramming of patient-specific somatic cells into induced pluripotent stem cells (iPSCs) allows the generation of iPSC-derived cardiomyocytes and iPSC-derived neuronal cells for later small molecule/antibody screening, drug development, and disease modelling. PONV, postoperative nausea and vomiting T A B L E 1 Commercially available ESC and iPSC lines for in vitro cell-based anaesthesia studies (Yuan et al, 2016) iPSC-CM (ReproCardio2 ® ) Propofol Toxicity GABA A (Kido et al, 2018) iPSC-CM (iCell ® ) Milrinone, citalopram, nifedipine, lidocaine EHT function Multiple (Mannhardt et al, 2017) Abbreviations: EHT, engineered heart tissue; NPC, neuronal progenitor cell; NSC, neuronal stem cell; OPRK1, κ-opioid receptor.…”

Section: Gpcrsmentioning

confidence: 99%

Induced pluripotent stem cells as a platform to understand patient‐specific responses to opioids and anaesthetics

Obal

2020

British J Pharmacology

View full text Add to dashboard Cite

Recent advances in human induced pluripotent stem cell (iPSC) technology may provide unprecedented opportunities to study patient‐specific responses to anaesthetics and opioids. In this review, we will (1) examine the advantages and limitations of iPSC technology, (2) summarize studies using iPSCs that have contributed to our current understanding of anaesthetics and opioid action on the cardiovascular system and central nervous system (CNS), and (3) describe how iPSC technology can be used to further develop personalized analgesic and sedative pharmacotherapies with reduced or minimal detrimental cardiovascular effects.

show abstract

Cytotoxicity of propofol in human induced pluripotent stem cell-derived cardiomyocytes

Cited by 16 publications

References 37 publications

Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction

Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction

The Basic Study of the Mechanism of Propofol-Related Infusion Syndrome Using a Murine Skeletal Muscle Injury Model

Induced pluripotent stem cells as a platform to understand patient‐specific responses to opioids and anaesthetics

Contact Info

Product

Resources

About