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mitochondria and cardiotoxity

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https://www.readbyqxmd.com/read/30063064/curcumin-attenuates-doxorubicin-induced-cardiotoxicity-via-suppressing-oxidative-stress-and-preventing-mitochondrial-dysfunction-mediated-by-14-3-3%C3%AE
#1
Huan He, Yong Luo, Yang Qiao, Zeyu Zhang, Dong Yin, Jianguo Yao, Jiegen You, Ming He
Doxorubicin (Dox) induces cardiotoxicity, thereby limiting its clinical application for chemotherapy of cancer. The mechanism of cardiotoxicity includes the production of excess intracellular ROS. 14-3-3s have been found to protect the myocardium against various types of injury. Curcumin (Cur) is a polyphenolic compound that is derived from turmeric and has multiple bioactivities, including anti-oxidative and radical-scavenging activities that exert cytoprotection. We hypothesize that the cardioprotective effects of Cur are exerted by regulating 14-3-3γ...
July 31, 2018: Food & Function
https://www.readbyqxmd.com/read/30025410/microrna-29b-regulates-the-mitochondria-dependent-apoptotic-pathway-by-targeting-bax-in-doxorubicin-cardiotoxicity
#2
Xibo Jing, Jingxiao Yang, Lu Jiang, Jianghong Chen, Haiyan Wang
BACKGROUND/AIMS: Myocardial apoptosis plays an important role in doxorubicin (Dox) cardiotoxicity. MicroRNA-29 (miR-29) is suggested to function as an anti-fibrotic factor with potential therapeutic effects on cardiac fibrosis. However, it has not been shown whether there is an association between miR-29b and myocardial apoptosis. METHODS: Male Wistar rats were transfected with miR-29b agomir by local delivery to the myocardium prior to Dox treatment. Rat cardiomyocytes were pretreated with miR-29b mimics or inhibitor followed by Dox incubation in vitro...
July 19, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30009776/triptolide-induces-p53-dependent-cardiotoxicity-through-mitochondrial-membrane-permeabilization-in-cardiomyocytes
#3
Yue Xi, Wenwen Wang, Li Wang, Ji Pan, Yisen Cheng, Feihai Shen, Zhiying Huang
Triptolide (TP), a major active component of Tripterygium wilfordii Hook f., is widely used in the treatment of inflammation and autoimmune disorders. Its clinical application is limited by severe adverse effects, especially cardiotoxicity. Accumulative evidences indicate that TP induces DNA damage by inhibiting RNA polymerase. Considering the relationship among DNA damage, p53, and the role of p53 in mitochondria-dependent apoptosis, we speculate that TP-induced cardiotoxicity results from p53 activation. In this study, the role of p53 in TP-induced cardiotoxicity was investigated in H9c2 cells, primary cardiomyocytes, and C57BL/6 genetic background p53-/- mice...
July 18, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29921817/mitochondria-targeting-small-molecules-effectively-prevent-cardiotoxicity-induced-by-doxorubicin
#4
REVIEW
Wei Shi, Hongkuan Deng, Jianyong Zhang, Ying Zhang, Xiufang Zhang, Guozhen Cui
Doxorubicin (Dox) is a chemotherapeutic agent widely used for the treatment of numerous cancers. However, the clinical use of Dox is limited by its unwanted cardiotoxicity. Mitochondrial dysfunction has been associated with Dox-induced cardiotoxicity. To mitigate Dox-related cardiotoxicity, considerable successful examples of a variety of small molecules that target mitochondria to modulate Dox-induced cardiotoxicity have appeared in recent years. Here, we review the related literatures and discuss the evidence showing that mitochondria-targeting small molecules are promising cardioprotective agents against Dox-induced cardiac events...
June 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29867492/salvianolic-acid-a-ameliorates-arsenic-trioxide-induced-cardiotoxicity-through-decreasing-cardiac-mitochondrial-injury-and-promotes-its-anticancer-activity
#5
Jing-Yi Zhang, Min Wang, Rui-Ying Wang, Xiao Sun, Yu-Yang Du, Jing-Xue Ye, Gui-Bo Sun, Xiao-Bo Sun
Arsenic trioxide (ATO) is used as a therapeutic agent in the treatment of acute promyelocytic leukemia (APL). The therapeutic use of arsenic is limited due to its severe cardiovascular side effects. The cardio-protective effect of salvianolic acid A (Sal A) against ATO cardiotoxicity has been reported. However, the distinct role of the mitochondria in the cardio-protection of Sal A is not understood. The aim of this study was to determine whether Sal A preconditioning protects against ATO-induced heart injury by maintaining cardiac mitochondrial function and biogenesis...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29775411/humanin-analogue-hng-enhances-the-protective-effect-of-dexrazoxane-against-doxorubicin-induced-cardiotoxicity
#6
YanHe Lue, Chen Gao, Ronald S Swerdloff, James Hoang, Rozeta Avetisyan, Yue Jia, Meng Rao, Shuxun Ren, Vince Atienza, Junyi Yu, Yie Zhang, Mengping Chen, Yang Song, Yibin Wang, Christina Wang
The chemotherapeutic effect of Doxorubicin (Dox) is limited by cumulative dose-dependent cardiotoxicity in cancer survivors. Dexrazoxane (DRZ) is approved to prevent Dox-induced cardiotoxicity. Humanin and its synthetic analog HNG have cytoprotective effect on the heart. To investigate the cardioprotective efficacy of HNG alone or in combination with DRZ against Dox-induced cardiotoxicity, eighty adult male mice were randomly divided into 8 groups to receive the following treatments via intraperitoneal injection: saline daily; HNG (5mg/kg) daily; DRZ (60mg/kg) weekly; Dox (3mg/kg) weekly; DRZ+HNG, Dox+HNG; Dox+DRZ and Dox+HNG+DRZ...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29765507/ex-vivo-cardiotoxicity-of-antineoplastic-casiopeinas-is-mediated-through-energetic-dysfunction-and-triggered-mitochondrial-dependent-apoptosis
#7
Christian Silva-Platas, César A Villegas, Yuriana Oropeza-Almazán, Mariana Carrancá, Alejandro Torres-Quintanilla, Omar Lozano, Javier Valero-Elizondo, Elena C Castillo, Judith Bernal-Ramírez, Evaristo Fernández-Sada, Luis F Vega, Niria Treviño-Saldaña, Héctor Chapoy-Villanueva, Lena Ruiz-Azuara, Carmen Hernández-Brenes, Leticia Elizondo-Montemayor, Carlos E Guerrero-Beltrán, Karla Carvajal, María E Bravo-Gómez, Gerardo García-Rivas
Casiopeinas are a group of copper-based antineoplastic molecules designed as a less toxic and more therapeutic alternative to cisplatin or Doxorubicin; however, there is scarce evidence about their toxic effects on the whole heart and cardiomyocytes. Given this, rat hearts were perfused with Casiopeinas or Doxorubicin and the effects on mechanical performance, energetics, and mitochondrial function were measured. As well, the effects of Casiopeinas-triggered cell death were explored in isolated cardiomyocytes...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29743983/chemotherapeutic-drugs-and-mitochondrial-dysfunction-focus-on-doxorubicin-trastuzumab-and-sunitinib
#8
REVIEW
Stefania Gorini, Antonella De Angelis, Liberato Berrino, Natalia Malara, Giuseppe Rosano, Elisabetta Ferraro
Many cancer therapies produce toxic side effects whose molecular mechanisms await full elucidation. The most feared and studied side effect of chemotherapeutic drugs is cardiotoxicity. Also, skeletal muscle physiology impairment has been recorded after many chemotherapeutical treatments. However, only doxorubicin has been extensively studied for its side effects on skeletal muscle. Chemotherapeutic-induced adverse side effects are, in many cases, mediated by mitochondrial damage. In particular, trastuzumab and sunitinib toxicity is mainly associated with mitochondria impairment and is mostly reversible...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29729358/doxorubicin-induced-mitophagy-and-mitochondrial-damage-is-associated-with-dysregulation-of-the-pink1-parkin-pathway
#9
Jian Yin, Jiabin Guo, Qiang Zhang, Lan Cui, Li Zhang, Tingfen Zhang, Jun Zhao, Jin Li, Alistair Middleton, Paul L Carmichael, Shuangqing Peng
The usefulness of doxorubicin (DOX), a potent anticancer agent, is limited by its cardiotoxicity. Mitochondria play a central role in DOX-induced cardiotoxicity though the precise mechanisms are still obscure. Increasing evidence indicates that excessive activation of mitophagy and mitochondrial dysfunction are key causal events leading to DOX-induced cardiac injury. The PINK1/parkin pathway has emerged as a critical pathway in regulation of mitophagy as well as mitochondrial function. The present study was aimed to investigate the role of PINK1/parkin pathway in DOX-induced mitochondrial damage and cardiotoxicity...
September 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29653124/doxorubicin-triggers-bioenergetic-failure-and-p53-activation-in-mouse-stem-cell-derived-cardiomyocytes
#10
Teresa Cunha-Oliveira, Luciana L Ferreira, Ana Raquel Coelho, Cláudia M Deus, Paulo J Oliveira
Doxorubicin (DOX) is a widely used anticancer drug that could be even more effective if its clinical dosage was not limited because of delayed cardiotoxicity. Beating stem cell-derived cardiomyocytes are a preferred in vitro model to further uncover the mechanisms of DOX-induced cardiotoxicity. Our objective was to use cultured induced-pluripotent stem cell(iPSC)-derived mouse cardiomyocytes (Cor.At) to investigate the effects of DOX on cell and mitochondrial metabolism, as well as on stress responses. Non-proliferating and beating Cor...
June 1, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29563880/antineoplastic-drug-induced-cardiotoxicity-a-redox-perspective
#11
REVIEW
Gilda Varricchi, Pietro Ameri, Christian Cadeddu, Alessandra Ghigo, Rosalinda Madonna, Giancarlo Marone, Valentina Mercurio, Ines Monte, Giuseppina Novo, Paolo Parrella, Flora Pirozzi, Antonio Pecoraro, Paolo Spallarossa, Concetta Zito, Giuseppe Mercuro, Pasquale Pagliaro, Carlo G Tocchetti
Antineoplastic drugs can be associated with several side effects, including cardiovascular toxicity (CTX). Biochemical studies have identified multiple mechanisms of CTX. Chemoterapeutic agents can alter redox homeostasis by increasing the production of reactive oxygen species (ROS) and reactive nitrogen species RNS. Cellular sources of ROS/RNS are cardiomyocytes, endothelial cells, stromal and inflammatory cells in the heart. Mitochondria, peroxisomes and other subcellular components are central hubs that control redox homeostasis...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29518932/diazoxide-improves-mitochondrial-connexin-43-expression-in-a-mouse-model-of-doxorubicin-induced-cardiotoxicity
#12
Michela Pecoraro, Michele Ciccarelli, Antonella Fiordelisi, Guido Iaccarino, Aldo Pinto, Ada Popolo
Doxorubicin (DOXO) administration induces alterations in Connexin 43 (Cx43) expression and localization, thus, inducing alterations in chemical and electrical signal transmission between cardiomyocytes and in intracellular calcium homeostasis even evident after a single administration. This study was designed to evaluate if Diazoxide (DZX), a specific opener of mitochondrial KATP channels widely used for its cardioprotective effects, can fight DOXO-induced cardiotoxicity in a short-time mouse model. DZX (20 mg/kg i...
March 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29397400/cell-death-mechanisms-of-the-anti-cancer-drug-etoposide-on-human-cardiomyocytes-isolated-from-pluripotent-stem-cells
#13
Harshal Nemade, Umesh Chaudhari, Aviseka Acharya, Jürgen Hescheler, Jan Georg Hengstler, Symeon Papadopoulos, Agapios Sachinidis
Etoposide (ETP) and anthracyclines are applied for wide anti-cancer treatments. However, the ETP-induced cardiotoxicity remains to be a major safety issue and the underlying cardiotoxic mechanisms are not well understood. This study is aiming to unravel the cardiotoxicity profile of ETP in comparison to anthracyclines using physiologically relevant human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). Using xCELLigence real-time cell analyser (RTCA), we found that single high dose of ETP induces irreversible increase in hPSC-CMs beating rate and decrease in beating amplitude...
April 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29348263/phosphoinositide-3-kinase-gamma-inhibition-protects-from-anthracycline-cardiotoxicity-and-reduces-tumor-growth
#14
Mingchuan Li, Valentina Sala, Maria Chiara De Santis, James Cimino, Paola Cappello, Nicola Pianca, Anna Di Bona, Jean Piero Margaria, Miriam Martini, Edoardo Lazzarini, Flora Pirozzi, Luca Rossi, Irene Franco, Julia Bornbaum, Jacqueline Heger, Susanne Rohrbach, Alessia Perino, Carlo G Tocchetti, Braulio H F Lima, Mauro M Teixeira, Paolo E Porporato, Rainer Schulz, Annalisa Angelini, Marco Sandri, Pietro Ameri, Sebastiano Sciarretta, Roberto César P Lima-Júnior, Marco Mongillo, Tania Zaglia, Fulvio Morello, Francesco Novelli, Emilio Hirsch, Alessandra Ghigo
Background -Anthracyclines, such as doxorubicin (DOX), are potent anti-cancer agents for the treatment of solid tumors and hematological malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of PI3Kγ in DOX-induced cardiotoxicity and the potential cardio-protective and anti-cancer effects of PI3Kγ inhibition. Methods -Mice expressing a kinase-inactive PI3Kγ or receiving PI3Kγ selective inhibitors were subjected to chronic DOX treatment. Cardiac function was analyzed by echocardiography and DOX-mediated signaling was assessed in whole hearts or in isolated cardiomyocytes...
January 18, 2018: Circulation
https://www.readbyqxmd.com/read/29331652/salinomycin-induces-primary-chicken-cardiomyocytes-death-via-mitochondria-mediated-apoptosis
#15
Xiuge Gao, Yani Zheng, Xiangchun Ruan, Hui Ji, Lin Peng, Dawei Guo, Shanxiang Jiang
Salinomycin, as a polyether ionophore antibiotic, is extensively used as a feed additive against coccidiosis in poultry and as a growth promoter of ruminants worldwide. Owing to its narrow therapeutic index, numerous intoxication have been reported in target/non-target animals by overdosage, misuse or drug interactions as well as human who consumed salinomycin accidently. Salinomycin-induced cardiotoxicity in chicken and non-target animals is considered as a major contributor to animal death. In the current study, we aim to elucidate the underlying mechanism of its myocardial toxicity using primary chicken myocardial cell as an in vitro model...
February 25, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29329420/pyrrolidine-dithiocarbamate-reverses-bcl-xl-mediated-apoptotic-resistance-to-doxorubicin-by-inducing-paraptosis
#16
Seok Soon Park, Dong Min Lee, Jun Hee Lim, Dongjoo Lee, Sang Jun Park, Hwan Myung Kim, Seonghyang Sohn, Gyesoon Yoon, Young Woo Eom, Seong-Yun Jeong, Eun Kyung Choi, Kyeong Sook Choi
Elevated Bcl-xL expression in cancer cells contributes to doxorubicin (DOX) resistance, leading to failure in chemotherapy. In addition, the clinical use of high-dose doxorubicin (DOX) in cancer therapy has been limited by issues with cardiotoxicity and hepatotoxicity. Here, we show that co-treatment with pyrrolidine dithiocarbamate (PDTC) attenuates DOX-induced apoptosis in Chang-L liver cells and human hepatocytes, but overcomes DOX resistance in Bcl-xL-overexpressing Chang-L cells and several hepatocellular carcinoma (HCC) cell lines with high Bcl-xL expression...
March 8, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29225006/mechanistic-studies-on-ketamine-induced-mitochondrial-toxicity-in-zebrafish-embryos
#17
Bonnie L Robinson, Melanie Dumas, Syed F Ali, Merle G Paule, Qiang Gu, Jyotshna Kanungo
Ketamine, a phencyclidine derivative, is an antagonist of the Ca2+ -permeable N-methyl-d-aspartate (NMDA)-type glutamate receptors. It is a pediatric anesthetic and has been implicated in developmental neurotoxicity. Ketamine has also been shown to deplete ATP in mammalian cells. Our previous studies showed that acetyl l-carnitine (ALCAR) prevented ketamine-induced cardiotoxicity and neurotoxicity in zebrafish embryos. Based on our finding that ALCAR's protective effect was blunted by oligomycin A, an inhibitor of ATP synthase, we further investigated the effects of ketamine and ALCAR on ATP levels, mitochondria and ATP synthase in zebrafish embryos...
December 7, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/29105555/toxicity-of-new-synthetic-amphetamine-drug-mephedrone-on-rat-heart-mitochondria-a-warning-for-its-abuse
#18
Parvaneh Naserzadeh, Farzaneh Jokar, Farzaneh Vafaei, Enayatollah Seydi, Jalal Pourahmad
1. Mephedrone, a new and popular amphetamine drug, is widely abused and is still legal in some parts around the world. Little data on mechanisms involved in mephedrone induced cardiotoxicity are available. 2. Therefore, we decided to explain the mechanisms of mephedrone cardiotoxicity by using mitochondria isolated from rat heart. The isolated heart mitochondria were incubated with different concentrations of mephedrone (5, 10 and 20 µM). 3. Results showed that mephedrone induced mitochondrial dysfunction via an increase in mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling and damage in the mitochondrial outer membrane (MOM) which is associated with the cytochrome c release...
November 28, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28993115/recurrent-exposure-to-ferric-oxide-nanoparticles-alters-myocardial-oxidative-stress-apoptosis-and-necrotic-markers-in-male-mice
#19
Vijayprakash Manickam, Madhivadhani Periyasamy, Vasanth Dhakshinamoorthy, Lakshmikanthan Panneerselvam, Ekambaram Perumal
The cardiotoxicity of iron oxide nanoparticles (Fe2 O3 -NPs) in mice was investigated. The mice were intraperitoneally administered with Fe2 O3 -NPs at the dose of 25 and 50 mg/kg bw for 30 days at seven days interval. In vivo MRI analysis reveals the Fe2 O3 -NPs accumulation in the cardiac system. Also, serum iron estimation and Prussian blue staining confirms the iron deposition in circulatory system. Cardiac dysfunction was assessed by ECG analysis and further validated by evaluating the functional markers such as cardiac Troponin-1 (cTnI) expression, AChE activity and levels of LDH and CK-MB in cardiac tissue...
December 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28931882/honokiol-protects-against-doxorubicin-cardiotoxicity-via-improving-mitochondrial-function-in-mouse-hearts
#20
Lizhen Huang, Kailiang Zhang, Yingying Guo, Fengyuan Huang, Kevin Yang, Long Chen, Kai Huang, Fengxue Zhang, Qinqiang Long, Qinglin Yang
Honokiol is a key component of a medicinal herb, Magnolia bark. Honokiol possesses potential pharmacological benefits for many disease conditions, especially cancer. Recent studies demonstrate that Honokiol exerts beneficial effects on cardiac hypertrophy and doxorubicin (Dox)-cardiotoxicity via deacetylation of mitochondrial proteins. However, the effects and mechanisms of Honokiol on cardiac mitochondrial respiration remain unclear. In the present study, we investigate the effect of Honokiol on cardiac mitochondrial respiration in mice subjected to Dox treatment...
September 20, 2017: Scientific Reports
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