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mitochondria and cardiotoxity

Taiyi Wang, Xiaonan Chen, Jiahui Yu, Qunqun Du, Jie Zhu, Mingzhu Yang, Honghua Wu, Meng Wang, Yan Zhu
Although the efficacy and the health care advantages of Chinese herbal medicine (CHM) have become increasingly recognized worldwide, the potential side effects and toxicity still restrict its broader application. This study established and applied an integrated platform anchored on automatic patch clamp system to screen and evaluate a collection of CHM extracts, compositions and monomeric compounds for in vitro cardiac toxicity. Of 1036 CHM samples screened, 2.79% significantly inhibited hERG channel activity...
December 14, 2018: American Journal of Chinese Medicine
Guo-Xing Wan, Lan Cheng, Hai-Lun Qin, Yun-Zhang Zhang, Ling-Yu Wang, Yong-Gang Zhang
The wide use of anthracyclines represented by doxorubicin (DOX) has benefited cancer patients, yet the clinical application is limited due to its cardiotoxicity. Although numerous evidences have supported a role of microRNAs (miRNAs) in DOX-induced myocardial damage, the exact etiology and pathogenesis remain largely obscure. In this study, we focused on the role of miR-15b-5p in DOX-induced cardiotoxicity. We employed a public miRNA and gene microarray to screen differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) in rat cardiomyocytes, and 33 DEMs including miR-15b-5p and 237 DEGs including Bmpr1a and Gata4 were identified...
December 7, 2018: Cardiovascular Toxicology
Payal Rana, Michael D Aleo, Mark Gosink, Yvonne Will
Mitochondrial toxicity has been shown to contribute to a variety of organ toxicities such as liver, cardiac and kidney. In the past decades, two high throughput applicable screening assays (isolated rat liver mitochondria; glucose-galactose grown HepG2 cells) to assess mitochondrial toxicity have been deployed in many pharmaceutical companies and numerous publications have demonstrated its usefulness for mechanistic investigations. However, only two publications have demonstrated the utility of these screens as a predictor of human drug induced liver injury...
December 10, 2018: Chemical Research in Toxicology
Siwen Li, Hongjing Zhao, Yu Wang, Yizhi Shao, Juanjuan Liu, Mingwei Xing
Arsenic-based drugs as food additive were used in poultry. However, excessive arsenic exposure can disturb myocardial cell metabolism, which results in the inhibition of growth and development of chickens. Since disordered mitochondria influences cardiac physiology and pathology, a better understanding of the mechanisms modulating cardiomyocyte mitochondria process is critical for identifying the potent detoxication targets under arsenic exposure in chickens. Male Hy-line chickens (1-day-old) were fed either a basal diet or an arsenic trioxide (As2O3)-supplemented diet containing 7...
October 18, 2018: Poultry Science
Adam J Smith, Peter J Gawne, Michelle T Ma, Philip J Blower, Richard Southworth, Nicholas J Long
Radiolabelled lipophilic cations that accumulate in mitochondria according to the magnitude of the mitochondrial membrane potential can be used to report non-invasively on mitochondrial dysfunction in cardiovascular disease, cardiotoxicity, and cancer. While several such cations are already commercially available for SPECT imaging, PET offers greater promise in terms of sensitivity, resolution, and capacity for dynamic imaging and pharmacokinetic modelling. We have therefore synthesised a series of three triarylphosphonium-functionalised DO3A chelators for positron emitter gallium-68, with differing alkyl-functionalisation motifs to provide opportunities for tunable lipophilicity as a means of optimising their pharmacokinetics...
October 17, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Rui Song, Yurong Yang, Han Lei, Guangxue Wang, Yong Huang, Wenlong Xue, Yinfang Wang, Lingling Yao, Yichun Zhu
Doxorubicin (Dox) is an efficacious antineoplastic drug but is limited used for its cardiotoxicity. Histone Deacetylase 6 (HDAC6) has been indicated to participate in cardiomyopathies, however, its role in Dox-induced cardiac injury is largely unknown. In this study, we firstly aimed to determine the role of HDAC6 in Dox-induced cardiomyopathy. Immunoblotting revealed that Dox increased HDAC6 protein level and activity and decreased α-tubulin acetylation level in vitro and vivo. HDAC6 knockout (HDAC6-/- ) mice showed obvious anti-Dox cardiotoxicity by conserved cardiac function monitored by echocardiography and the protection was reversed by Nocodazole, one drug lowering α-tubulin acetylation...
October 10, 2018: Journal of Molecular and Cellular Cardiology
Wen-Juan Li, Xian-Yi Zhang, Rui-Ting Wu, Ye-Hao Song, Ming-Yong Xie
The present study aimed to determine the cardioprotective effect of Ganoderma atrum polysaccharide (PSG-1) in doxorubicin (DOX)-treated mice and its underlying mechanism. Results indicated that PSG-1 treatment significantly alleviated DOX-induced myocardial damage via attenuating apoptosis and maintaining the structure of myocardial mitochondria. Meanwhile, PSG-1-evoked cardioprotection was associated with an increase of manganese superoxide dismutase activity and decrease of caspases activities. Moreover, administration of PSG-1 suppressed DOX-induced mitochondrial disorders, which was evidenced by reducing reactive oxygen species, elevating mitochondrial membrane potential and inhibiting the opening of mitochondrial permeability transition pore...
December 15, 2018: Carbohydrate Polymers
Jun Li, Ran Duan, Yingying Zhang, Xin Zhao, Yanxin Cheng, Yongxue Chen, Jinge Yuan, Hong Li, Jianping Zhang, Li Chu, Dengyun Xia, Senming Zhao
In order to determine the role of the adrenergic system in bupivacaine-induced cardiotoxicity, a series of experiments were performed. In an animal experiment, male Sprague-Dawley (SD) rats under chloral hydrate anesthesia received intravenous bupivacaine, followed by an intravenous injection of adrenalin or isoprenalin, and the electrocardiogram (ECG), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum rate of rise of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure decrease (-dP/dtmax) were continually monitored...
2018: PloS One
Philippe Hantson
BACKGROUND: Dilated cardiomyopathy is a frequent disease responsible for 40-50% of cases of heart failure. Idiopathic cardiomyopathy is a primary disorder often related to familial/genetic predisposition. Before the diagnosis of idiopathic cardiomyopathy is made, clinicians must not only rule out viral and immune causes, but also toxic causes such as drugs, environmental agents, illicit substances and natural toxins. OBJECTIVE: The objective of this review is to present recent data on the mechanisms underlying toxic cardiomyopathy...
September 27, 2018: Clinical Toxicology
Ting Chen, Zhiyong Deng, Ruilian Zhao, Hongmei Shen, Wenhui Li
Backgrounds. Doxorubicin (DOX) is an effective therapeutic drug for malignant tumors; however, its clinical applications were limited by its side effects, especially the cardiotoxicity caused by ROS-mediated p53 and MAPK signal pathways' activation-induced cell apoptosis. Sanyang Xuedai mixture (SYKT) has been reported as an antioxidant agent and attenuated DOX-induced cardiotoxicity by targeting ROS-mediated apoptosis, but the mechanisms are still not fully delineated. Objective. This study aimed at investigating whether SYKT alleviated DOX-induced cardiotoxicity by inhibiting ROS-mediated apoptosis and elucidating the role of ROS-mediated p53 and MAPK signal pathways' activation in this process...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Xilei Xie, Fuyan Tang, Guangzhao Liu, Yong Li, Xingxing Su, Xiaoyun Jiao, Xu Wang, Bo Tang
Anthracyclines rank among the most efficacious anticancer medications. However, their clinical utility and oncologic efficacy are severely compromised by the cardiotoxicity risk facing the early-diagnosis difficulty and their unclear molecular mechanism. Herein, a two-photon-excitable and near-infrared-emissive fluorescent probe, TPNIR-FP, was fabricated and endowed with extraordinary specificity and sensitivity and a rapid response toward peroxynitrite (ONOO- ), as well as mitochondria-targeting ability. With the aid of TPNIR-FP, we demonstrate that mitochondrial ONOO- is upregulated in the early stage and contributes to the onset and progression of anthracycline cardiotoxicity in cardiomyocyte and mouse models; therefore, it represents an early biomarker to predict subclinical cardiotoxicity induced by drug challenge...
October 2, 2018: Analytical Chemistry
Meric A Altinoz, Ayhan Bilir, İlhan Elmaci
BACKGROUND: PPAR-δ is a transcription factor which has crucial roles in stimulating oligodendroglial differentiation and myelination and its activation was also shown to differentiate malignant C6 glioma cells into oligodendrocytes. OBJECTIVE: One of the ligands of PPAR-δ is erucic acid (EA), an edible omega-9 fatty acid consumed more by Asian populations and exists highly in Chinese womens milk. There exist epidemiological evidence that pediatric brain tumor incidence is among the lowest in the Chinese population...
October 1, 2018: Chemico-biological Interactions
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...
August 15, 2018: Food & Function
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...
2018: Cellular Physiology and Biochemistry
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...
September 15, 2018: Toxicology and Applied Pharmacology
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
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
Yanhe Lue, Chen Gao, Ronald Swerdloff, James Hoang, Rozeta Avetisyan, Yue Jia, Meng Rao, Shuxun Ren, Vince Atienza, Junyi Yu, Ye 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 a cytoprotective effect on the heart. To investigate the cardioprotective efficacy of HNG alone or in combination with DRZ against Dox-induced cardiotoxicity, 80 adult male mice were randomly divided into 8 groups to receive the following treatments via intraperitoneal injection: saline dailym HNG (5 mg/kg) daily, DRZ (60 mg/kg) weekly, Dox (3 mg/kg) weekly, DRZ + HNG, Dox + HNG, Dox + DRZ, and Dox + HNG + DRZ...
September 1, 2018: American Journal of Physiology. Heart and Circulatory Physiology
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
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
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