Rotenone and 3-bromopyruvate toxicity impacts electrical and structural cardiac remodeling in rats

Zhan, Chengchuang; Liu, Guangzhong; Li, Jianqiang; Li, Guangnan; Li, Tiankai; Zhao, Hongyan; Li, Luyifei; Yang, Wen; Bai, Nan; Zheng, Min; Yang, Jiao; Liu, Weimin

doi:10.1016/j.toxlet.2019.09.024

Cited by 14 publications

(11 citation statements)

References 48 publications

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“…All pyrethroids but tetramethrin demonstrated broad activity in VT assays, and many studies have reported that ROS generation in heart tissues has been implicated in pyrethroid toxicity. , None of the pyrethroids display activity in assays associated with oxidative stress or MtDys at sub-cytotoxic concentrations, but 13% and 80% of them were active against assays associated with oxidative stress and MtDys, respectively, at higher concentrations. Rotenone is a widely used pesticide and a well-established mitochondrial toxicant, which was recently shown to cause fatal arrhythmias in rats . In CardioToxPi, it exhibited activity in assays associated with MtDys, TR, and NR.…”

Section: Results and Discussionmentioning

confidence: 99%

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High-Throughput Screening to Identify Chemical Cardiotoxic Potential

Krishna

Berridge

Kleinstreuer

2020

Chem. Res. Toxicol.

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Cardiovascular (CV) disease is one of the most prevalent public health concerns, and mounting evidence supports the contribution of environmental chemicals to CV disease burden. In this study, we performed cardiotoxicity profiling for the Tox21 chemical library by focusing on high-throughput screening (HTS) assays whose targets are associated with adverse events related to CV failure modes. Our objective was to develop new hypotheses around environmental chemicals of potential interest for adverse CV outcomes using Tox21/ToxCast HTS data. Molecular and cellular events linked to six failure modes of CV toxicity were cross-referenced with 1399 Tox21/ToxCast assays to identify cardio-relevant bioactivity signatures. The resulting 40 targets, measured in 314 assays, were integrated via a ToxPi visualization tool and ranking system to prioritize 1138 chemicals based upon formal integration across multiple domains of information. Filtering was performed based on cytotoxicity and generalized cell stress endpoints to try and isolate chemicals with effects specific to CV biology, and bioactivity- and structure-based clustering identified subgroups of chemicals preferentially affecting targets such as ion channels and vascular tissue biology. Our approach identified drugs with known cardiotoxic effects, such as estrogenic modulators like clomiphene and raloxifene, anti-arrhythmic drugs like amiodarone and haloperidol, and antipsychotic drugs like chlorpromazine. Several classes of environmental chemicals such as organotins, bisphenol-like chemicals, pesticides, and quaternary ammonium compounds demonstrated strong bioactivity against CV targets; these were compared to existing data in the literature (e.g., from cardiomyocytes, animal data, or human epidemiological studies) and prioritized for further testing.

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Section: Results and Discussionmentioning

confidence: 99%

“…Interestingly, it shows activity across all three ion channel assays (sodium-, potassium-, and calcium-gated channels). Similarly, exposure to rotenone also leads to pro-arrhythmic effect due to the prolonged QTc . Exposure to a high dose of diethylstilbestrol induced an eccentric hypertrophy in adult mice .…”

Section: Results and Discussionmentioning

confidence: 99%

High-Throughput Screening to Identify Chemical Cardiotoxic Potential

Krishna

Berridge

Kleinstreuer

2020

Chem. Res. Toxicol.

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“…Clinical studies have shown that the expression of BAX was increased in cardiovascular patients, including arrhythmia [32], and caspase3 variants was susceptible to atrial brillation (AF). Myocardial apoptosis can cause electrical and structural cardiac remodeling [33]; and as the important apoptotic factors, the expression of CASP8, CASP9, BAX was altered in many cardiovascular disease (e.g. ichaemia/reperfusion [34], AF [35]).…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms of Notopterygii Rhizoma Et Radix for the Treatment of Arrhythmia Based on Network Pharmacology

Wei

Tan

et al. 2021

Preprint

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Background Many experiments showed that Notopterygii Rhizoma Et Radix (NRR) can resist arrhythmia, but the mechanism of its action has not clear. Here, we investigated the possible mechanisms of NRR by network pharmacology and molecular docking and verified them experimentally. Methods Active componds and targets of NRR were retrieved by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database andAnalysis Platform, SymMap, and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases. Arrhythmia-related targets were acquired from Comparative Toxicogenomics Database (CTD) and GeneCards databases. Overlapping targets of NRR associated with arrhythmia were acquired via Venn diagram. DAVID was applied for GO and KEGG pathway analyses. Cytoscape software and its plug-in were used for PPI network construction, module division and hub nodes screening. AutoDock Vina and qRT-PCR were carried out for validation. Results The 21 active compounds and 57 targets were obtained. Of these, coumarin was the predominant category including 15 components and 31 targets. The 5 key targets of NRR in treating arrhythmia, and these targets are involved in the apoptotic process, extrinsic apoptotic signaling pathway in absence of ligand, endopeptidase activity involved in apoptotic process by cytochrome c. The main pathways are p53 signaling pathway, Hepatitis B and Apoptosis. The results of molecular docking and qRT-PCR display good effect on hub node regulation in NRR treatment. Conclusion NRR plays an important role in anti-apoptotic mediated by modulating p53 signaling pathway, which may provide insight into future research and clinical applications in arrhythmia therapy.

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“…Rabbit anti-5HT 1A (1:1000, Bioss, bs-1124R) and rabbit anti-5HT 2A (1:1000, Bioss, bs-1056R) were used as the primary antibodies. Β-actin expression was determined using an antiβ-actin antibody (1:1000, Servicebio, GB12001) as an internal control (Zhan et al, 2020). The immunoblots were then visualized using an ECL Western Blot Detection System (Millipore Corporation, Billerica, MA, USA) and quantified with Image J software.…”

Section: Western Blot Analysismentioning

confidence: 99%

Armillaria mellea fermentation liquor ameliorates p‐chlorophenylalanine‐induced insomnia associated with the modulation of serotonergic system and gut microbiota in rats

Yao

Duan

et al. 2022

Journal of Food Biochemistry

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In China, Armillaria mellea (Vahl) P. Kumm. has been used as a folk medicine to treat insomnia for several hundred years. However, the underlying mechanisms involved are currently unknown. In this study, the anti-insomnia efficacy of A. mellea fermentation liquor (AFL) was evaluated in p-chlorophenylalanine-induced insomnia rats by measuring the serotonergic systems and gut microbiota. Our results demonstrate that all doses of AFL significantly reduced locomotor activity and alleviated decreasing weights in insomnia rats. Further, AFL exhibited better sedative effects by reducing sleep latency and increasing sleep duration in pentobarbital-treated rats. AFL treatment also elevated serum glutathione peroxidase and superoxide dismutase levels, while reducing serum interleukin-6, tumor necrosis factorα, and interleukin-1β levels. Furthermore, AFL alleviated insomnia by enhancing 5-hydroxytryptamine content and the expression 5-HT 1A and 5-HT 2A receptor in the hippocampus. Meanwhile, AFL treatment normalized the composition of gut microbiota in insomnia-model rats, while increasing relative abundance of Lachnospiraceae, Ruminococcaceae, and Saccharimonadaceae restores the gut microbial ecosystem altered in insomnia rats.The experiments show that A. mellea alleviated insomnia by modulating serotonergic system and gut microbiota. Practical applicationsInsomnia has become a serious health issue of global concern. As a well-known traditional Chinese medicine, Armillaria mellea has been clinically employed in the treatment of insomnia for centuries in Asia with significant efficacy. In the present study, we firstly reported A. mellea fermentation liquor potentially relieved insomnia rats by alteration of gut microbiota and serotonergic systems and could guide future clinical studies. As a popular edible and medicinal mushroom, A. mellea also can be potentially used in the development and production of novel food products in the future.

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Rotenone and 3-bromopyruvate toxicity impacts electrical and structural cardiac remodeling in rats

Cited by 14 publications

References 48 publications

High-Throughput Screening to Identify Chemical Cardiotoxic Potential

High-Throughput Screening to Identify Chemical Cardiotoxic Potential

Molecular Mechanisms of Notopterygii Rhizoma Et Radix for the Treatment of Arrhythmia Based on Network Pharmacology

Armillaria mellea fermentation liquor ameliorates p‐chlorophenylalanine‐induced insomnia associated with the modulation of serotonergic system and gut microbiota in rats

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