Comprehensive review of cardiovascular toxicity of drugs and related agents

Mladěnka, Přemysl; Applová, Lenka; Patočka, Jiří; Costa, Vera Marisa; Remião, Fernando; Pourová, Jana; Mladěnka, Aleš; Karlíčková, Jana; Jahodár, L; Vopršalová, Marie; Varner, Kurt J.; Štěrba, Martin; Tox-Oer,; Researchers, Cardiotox Hradec Králové

doi:10.1002/med.21476

Cited by 192 publications

(107 citation statements)

References 532 publications

(1,153 reference statements)

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“…Cardiovascular toxicity is a major limiting factor in drug development and requires multiple cost-effective models to perform toxicological evaluation [73,74] . Zebrafish is now a well-validated animal model to study treatment with small molecules, as well as to elucidate biological functions, and deciphering the mechanism of bioactive compounds [74] .…”

Section: Cardiotoxicity Of Small Molecules: Drug Screening Using the mentioning

confidence: 99%

Zebrafish as Toxicological model for screening and recapitulate human diseases

Caballero¹,

Candiracci²

2018

JUMD

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Embryonic and larval Danio rerio (zebrafish) is increasingly used as a toxicological model to conduct rapid in vivo tests and developmental toxicity assays; the zebrafish features high genetic homology to mammals, robust, phenotypes, highthroughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. New methodologies of genome editing as CRISPR/Cas9; ZFN and TALEN make it a suitable model to perform studies to pair human genetic diseases as well. This review surveys recent studies employing zebrafish as experimental model, comparing it with other in vivo and in vitro models, presenting zebrafish as a potent vertebrate tool to evaluate drug toxicity and efficacy in order to facilitate more extensive, easy and comprehensive knowledge of new generation drugs.

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Section: Cardiotoxicity Of Small Molecules: Drug Screening Using the mentioning

confidence: 99%

Zebrafish as Toxicological model for screening and recapitulate human diseases

Caballero¹,

Candiracci²

2018

JUMD

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“…The human ether-a-go-go-related gene (hERG) encodes a potassium channel protein, which is important for cardiac electrical activity and the coordination of heartbeat. Blockade of the hERG potassium channel can result in a potentially fatal disorder called long QT syndrome, as well as serious cardiotoxicity, which has led to the withdrawal of several marketed drugs and the failure of many drug research and development projects (Fermini and Fossa, 2003;Recanatini et al, 2005;Sanguinetti and Tristani-Firouzi, 2006;Bowes et al, 2012;Nachimuthu et al, 2012;Zhang et al, 2012;Shah, 2013;Kalyaanamoorthy and Barakat, 2018;Mladenka et al, 2018). Therefore, drug candidates that can bind with hERG should be eliminated as early as possible in drug discovery studies.…”

Section: Introductionmentioning

confidence: 99%

Capsule Networks Showed Excellent Performance in the Classification of hERG Blockers/Nonblockers

et al. 2020

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Capsule networks (CapsNets), a new class of deep neural network architectures proposed recently by Hinton et al., have shown a great performance in many fields, particularly in image recognition and natural language processing. However, CapsNets have not yet been applied to drug discovery-related studies. As the first attempt, we in this investigation adopted CapsNets to develop classification models of hERG blockers/ nonblockers; drugs with hERG blockade activity are thought to have a potential risk of cardiotoxicity. Two capsule network architectures were established: convolution-capsule network (Conv-CapsNet) and restricted Boltzmann machine-capsule networks (RBM-CapsNet), in which convolution and a restricted Boltzmann machine (RBM) were used as feature extractors, respectively. Two prediction models of hERG blockers/nonblockers were then developed by Conv-CapsNet and RBM-CapsNet with the Doddareddy's training set composed of 2,389 compounds. The established models showed excellent performance in an independent test set comprising 255 compounds, with prediction accuracies of 91.8 and 92.2% for Conv-CapsNet and RBM-CapsNet models, respectively. Various comparisons were also made between our models and those developed by other machine learning methods including deep belief network (DBN), convolutional neural network (CNN), multilayer perceptron (MLP), support vector machine (SVM), k-nearest neighbors (kNN), logistic regression (LR), and LightGBM, and with different training sets. All the results showed that the models by Conv-CapsNet and RBM-CapsNet are among the best classification models. Overall, the excellent performance of capsule networks achieved in this investigation highlights their potential in drug discoveryrelated studies.

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“…Exposing to nicotine stimulates macrophages to release pro-inflammatory mediators. Then, they activate neutrophils to synthesize free radicals, elastase and inflammatory cytokines including TNF--6 and IL-1b [80]. It has been shown that inflammatory cytokines have an important role in the development and progression of chronic renal failure (CRF) [81].…”

Section: Effects On the Kidneymentioning

confidence: 99%

A Mechanistic Review of Nicotine Toxicity with Recent Updates

Ahmadi¹

2019

IJBP

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There are concerns about the spread of cigarette smoking and nicotine is the most harmful agent in cigarette smoke. The statics show the growing use of cigarette smoking. Nicotine is an alkaloid and is present in the leaves of tobacco where it acts as a botanical insecticide. It represents 90% of total alkaloid in cigarette smoke. Osteoporosis, lung and kidney injuries, diseases of respiratory and cardiovascular systems, and increased risk of malignancy are just a few of toxic effects of nicotine on the body. Nicotine exerts its harmful effects via oxidative stress pathway, so that it enhances the production of reactive oxygen species (ROS) and then negatively affects different organs and systems of body. This review provides a comprehensive review of detrimental effects of nicotine on the body and then describes its mechanism of toxicity.

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Comprehensive review of cardiovascular toxicity of drugs and related agents

Cited by 192 publications

References 532 publications

Zebrafish as Toxicological model for screening and recapitulate human diseases

Zebrafish as Toxicological model for screening and recapitulate human diseases

Capsule Networks Showed Excellent Performance in the Classification of hERG Blockers/Nonblockers

A Mechanistic Review of Nicotine Toxicity with Recent Updates

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