Acetylcholinesterase inhibitor ameliorates doxorubicin-induced cardiotoxicity through reducing RIP1-mediated necroptosis

Khuanjing, Thawatchai; Ongnok, Benjamin; Maneechote, Chayodom; Siri‐Angkul, Natthaphat; Prathumsap, Nanthip; Arinno, Apiwan; Chunchai, Titikorn; Arunsak, Busarin; Chattipakorn, Nipon

doi:10.1016/j.phrs.2021.105882

Cited by 35 publications

(38 citation statements)

References 52 publications

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“…In addition, cardiac mitochondrial swelling was also determined by measuring the change in absorbance density under a spectrophotometer. The decrease in absorbance of the suspension at 540 nm indicates mitochondrial swelling [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

“…Biomarkers of cardiac injury, including the levels of cardiac troponin-I (cTnI) and N-terminal pro B-type natriuretic peptide (NT-proBNP) (MyBioSource, Inc., San Diego, USA), were determined using ELISA assay kits in accordance with the manufacturer’s instructions [ 23 ]. For oxidative stress, the levels of malondialdehyde (MDA) concentrations in serum and cardiac tissue were determined using the thiobarbituric acid method and measured with the high-performance liquid chromatography (HPLC) system as previously described [ 23 , 25 ].…”

Section: Methodsmentioning

confidence: 99%

“…Freshly-isolated mitochondria were stained with either 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolecar bocyanine iodide (JC-1, Sigma-Aldrich, Missouri, USA) or dichlorohydrofluorescein diacetate (DCFDA, Sigma-Aldrich, Missouri, USA) for the determination of ΔΨm (485 nm) or mtROS (485 nm) using a spectrophotometer (Gen5 Microplate Reader, BioTek Instruments, Vermont, USA) [22][23][24]. In addition, cardiac mitochondrial swelling was also determined by measuring the change in absorbance density under a spectrophotometer.…”

Section: Determination Of Cardiac Mitochondrial Membrane Potential (δ...mentioning

confidence: 99%

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GSDMD-mediated pyroptosis dominantly promotes left ventricular remodeling and dysfunction in post-myocardial infarction: a comparison across modes of programmed cell death and mitochondrial involvement

et al. 2023

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Background Myocardial infarction (MI) has recently accounted for more than one-third of global mortality. Multiple molecular pathological pathways, such as oxidative stress, inflammation, and mitochondrial dysfunction, have been recognized as possible mechanisms in the development of MI. Furthermore, different phases of ischemic injury following the progression of MI were also associated with multiple types of programmed cell death (PCDs), including apoptosis, necroptosis, ferroptosis, and pyroptosis. However, it remains unknown whether which types of PCDs play the most dominant role in post-myocardial infarction (post-MI). Method In this study, we used a preclinical rat model of MI induced by permanent left anterior descending coronary artery (LAD) ligation (n = 6) or a sham operated rat model (n = 6). After a 5-week experiment, cardiac function and morphology, mitochondrial studies, and molecular signaling analysis of PCDs were determined. Results Herein, we demonstrated that post-MI rats had considerably impaired cardiac geometry, increased oxidative stress, myocardial injuries, and subsequently contractile dysfunction. They also exhibited worsened cardiac mitochondrial function and dynamic imbalance. More importantly, we found that post-MI mediated abundant myocardial cell death through multiple PCDs, including apoptosis, necroptosis, and pyroptosis, but not ferroptosis. Conclusion In this study, we provide the first insights into the mechanism of PCDs by pyroptosis, which is leveraged as the most dominant mode of cell death after MI.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Determination Of Cardiac Mitochondrial Membrane Potential (δ...mentioning

confidence: 99%

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GSDMD-mediated pyroptosis dominantly promotes left ventricular remodeling and dysfunction in post-myocardial infarction: a comparison across modes of programmed cell death and mitochondrial involvement

et al. 2023

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“…Based on immunofluorescence analysis of TOM20, mitochondrial distribution and mitochondrial network disruption, as well as mitophagy, were revealed in DOX-treated neonatal rat ventricular myocytes [ 87 , 88 ]. To mimic human anticancer therapy, the administration schedule was conducted by multiple administrations at separate time points, including 3 mg/kg every other day for a cumulative dose of 9 mg/kg [ 99 ], twice a week for three weeks to attain a 9 mg/kg cumulative dose [ 100 ], 6 doses of 3 mg/kg [ 101 ], 2–2.5 mg/kg/48 h over 12 days [ 94 ], 2 mg/kg for 10 consecutive days [ 102 ], 5 mg/kg once a week to a total of 20 mg/kg [ 103 ], or two doses of 10 mg/kg [ 104 ]. Of note, a cumulative dose of 20 mg/kg in adult mice roughly corresponds to 120 mg/m 2 in humans, which is much lower than the maximum lifelong dose of 400–550 mg/m 2 [ 105 ].…”

Section: Main Properties Of Mitochondria and Drug-induced Mitochondri...mentioning

confidence: 99%

Assessing Drug-Induced Mitochondrial Toxicity in Cardiomyocytes: Implications for Preclinical Cardiac Safety Evaluation

Tang

Wang

et al. 2022

Pharmaceutics

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Drug-induced cardiotoxicity not only leads to the attrition of drugs during development, but also contributes to the high morbidity and mortality rates of cardiovascular diseases. Comprehensive testing for proarrhythmic risks of drugs has been applied in preclinical cardiac safety assessment for over 15 years. However, other mechanisms of cardiac toxicity have not received such attention. Of them, mitochondrial impairment is a common form of cardiotoxicity and is known to account for over half of cardiovascular adverse-event-related black box warnings imposed by the U.S. Food and Drug Administration. Although it has been studied in great depth, mitochondrial toxicity assessment has not yet been incorporated into routine safety tests for cardiotoxicity at the preclinical stage. This review discusses the main characteristics of mitochondria in cardiomyocytes, drug-induced mitochondrial toxicities, and high-throughput screening strategies for cardiomyocytes, as well as their proposed integration into preclinical safety pharmacology. We emphasize the advantages of using adult human primary cardiomyocytes for the evaluation of mitochondrial morphology and function, and the need for a novel cardiac safety testing platform integrating mitochondrial toxicity and proarrhythmic risk assessments in cardiac safety evaluation.

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“…Although there is no consensus on the role of mitophagy in AIC currently, several agents have been reported to alleviate AIC by correcting Dox-induced excessive mitophagy in cardiomyocytes. The acetylcholinesterase inhibitor donepezil was found to attenuate mitochondrial injury by blocking mitophagy and autophagy flux in dox-treated rat cardiomyocytes, leading to decreased levels of inflammatory cytokines and ROS production and rescue receptor-interacting protein kinase 1- (RIP1-) mediated necroptosis [ 202 ]. In addition, liensinine, a novel mitophagy inhibitor, has also been shown to have a significant therapeutic effect on AIC, and the suppression of Dox-related mitophagy and phosphorylation of Drp1 at Ser616 may account for the therapeutic mechanisms of this bioactive compound [ 57 ].…”

Section: Therapeutic Outlookmentioning

confidence: 99%

The Role of Mitochondrial Quality Control in Anthracycline-Induced Cardiotoxicity: From Bench to Bedside

Lin

Peng

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cardiotoxicity is the major side effect of anthracyclines (doxorubicin, daunorubicin, epirubicin, and idarubicin), though being the most commonly used chemotherapy drugs and the mainstay of therapy in solid and hematological neoplasms. Advances in the field of cardio-oncology have expanded our understanding of the molecular mechanisms underlying anthracycline-induced cardiotoxicity (AIC). AIC has a complex pathogenesis that includes a variety of aspects such as oxidative stress, autophagy, and inflammation. Emerging evidence has strongly suggested that the loss of mitochondrial quality control (MQC) plays an important role in the progression of AIC. Mitochondria are vital organelles in the cardiomyocytes that serve as the key regulators of reactive oxygen species (ROS) production, energy metabolism, cell death, and calcium buffering. However, as mitochondria are susceptible to damage, the MQC system, including mitochondrial dynamics (fusion/fission), mitophagy, mitochondrial biogenesis, and mitochondrial protein quality control, appears to be crucial in maintaining mitochondrial homeostasis. In this review, we summarize current evidence on the role of MQC in the pathogenesis of AIC and highlight the therapeutic potential of restoring the cardiomyocyte MQC system in the prevention and intervention of AIC.

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Acetylcholinesterase inhibitor ameliorates doxorubicin-induced cardiotoxicity through reducing RIP1-mediated necroptosis

Cited by 35 publications

References 52 publications

GSDMD-mediated pyroptosis dominantly promotes left ventricular remodeling and dysfunction in post-myocardial infarction: a comparison across modes of programmed cell death and mitochondrial involvement

GSDMD-mediated pyroptosis dominantly promotes left ventricular remodeling and dysfunction in post-myocardial infarction: a comparison across modes of programmed cell death and mitochondrial involvement

Assessing Drug-Induced Mitochondrial Toxicity in Cardiomyocytes: Implications for Preclinical Cardiac Safety Evaluation

The Role of Mitochondrial Quality Control in Anthracycline-Induced Cardiotoxicity: From Bench to Bedside

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