Chemotherapy‐associated cardiomyopathy: Mechanisms of toxicity and cardioprotective strategies

2021 ◽  
Author(s):  
Justin A. Veeder ◽  
Lauren N. Hothem ◽  
Amber E. Cipriani ◽  
Brian C. Jensen ◽  
Jo E. Rodgers
Keyword(s):  
Mechanisms Of Toxicity

Toxicology

2017 ◽  
Author(s):  
Robert Laumbach ◽  
Michael Gochfeld
Keyword(s):  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Toxicity Testing ◽  
The Body ◽  
Toxic Substances ◽  
Basic Principles ◽  
Practical Applications ◽  
Mechanisms Of Toxicity ◽  
Body Distribution ◽  
Threshold Doses

This chapter describes the basic principles of toxicology and their application to occupational and environmental health. Topics covered include pathways that toxic substances may take from sources in the environment to molecular targets in the cells of the body where toxic effects occur. These pathways include routes of exposure, absorption into the body, distribution to organs and tissues, metabolism, storage, and excretion. The various types of toxicological endpoints are discussed, along with the concepts of dose-response relationships, threshold doses, and the basis of interindividual differences and interspecies differences in response to exposure to toxic substances. The diversity of cellular and molecular mechanisms of toxicity, including enzyme induction and inhibition, oxidative stress, mutagenesis, carcinogenesis, and teratogenesis, are discussed and the chapter concludes with examples of practical applications in clinical evaluation and in toxicity testing.

Cyanobacterial Neurotoxins: Their Occurrence and Mechanisms of Toxicity

2017 ◽  
Vol 33 (1) ◽  
pp. 168-177 ◽  
Author(s):  
Kenneth J. Rodgers ◽  
Brendan J. Main ◽  
Kate Samardzic
Keyword(s):  
Mechanisms Of Toxicity

scholarly journals Transcriptome Profile Alterations with Carbon Nanotubes, Quantum Dots, and Silver Nanoparticles: A Review

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 794
Author(s):  
Cullen Horstmann ◽  
Victoria Davenport ◽  
Min Zhang ◽  
Alyse Peters ◽  
Kyoungtae Kim
Keyword(s):  
Carbon Nanotubes ◽  
Quantum Dots ◽  
High Throughput Sequencing ◽  
The Body ◽  
Rna Seq ◽  
Mechanisms Of Toxicity ◽  
Promising Tool ◽  
Engineered Nanomaterial ◽  
Next Generation Sequencing Ngs ◽  
Transcriptomic Changes

Next-generation sequencing (NGS) technology has revolutionized sequence-based research. In recent years, high-throughput sequencing has become the method of choice in studying the toxicity of chemical agents through observing and measuring changes in transcript levels. Engineered nanomaterial (ENM)-toxicity has become a major field of research and has adopted microarray and newer RNA-Seq methods. Recently, nanotechnology has become a promising tool in the diagnosis and treatment of several diseases in humans. However, due to their high stability, they are likely capable of remaining in the body and environment for long periods of time. Their mechanisms of toxicity and long-lasting effects on our health is still poorly understood. This review explores the effects of three ENMs including carbon nanotubes (CNTs), quantum dots (QDs), and Ag nanoparticles (AgNPs) by cross examining publications on transcriptomic changes induced by these nanomaterials.

Inspiration and Exasperation: The Challenges of Inhaled Biologics

2021 ◽  
pp. 019262332098471
Author(s):  
Peter Hall ◽  
John L. Vahle ◽  
Karyn Colman
Keyword(s):  
Nucleic Acids ◽  
Scientific Knowledge ◽  
Human Disease ◽  
Regulatory Approval ◽  
Special Edition ◽  
Mechanisms Of Toxicity ◽  
Dornase Alfa

The delivery of biotherapeutic molecules (antibodies, proteins, peptides) and nucleic acids via the respiratory route has presented challenges for regulatory approval, due in part to a lack of understanding of the expected pathology, mechanisms of toxicity, and immunogenicity induced by the inhalation route. Although the first inhaled biotherapeutic was approved some time ago (Dornase Alfa, Pulmozyme; Genetech, 1993), no other inhaled biotherapeutics have been marketed for the treatment of human disease other than the inhaled insulins (Exubera; Pfizer, 2006 and Afrezza; Mannkind Corporation, 2014). As a result, scientific knowledge within the toxicologic pathology community is fragmented with precious little publicly available data. Therefore, one of the aims of this special edition was to generate a collection of manuscripts that pathologists and toxicologists could refer in order to understand the pathology, mechanisms of toxicity, immunogenicity, and challenges associated with the development of inhaled biotherapeutics.

scholarly journals Human Neuronal Cell Lines as An In Vitro Toxicological Tool for the Evaluation of Novel Psychoactive Substances

2021 ◽  
Vol 22 (13) ◽  
pp. 6785
Author(s):  
Valeria Sogos ◽  
Paola Caria ◽  
Clara Porcedda ◽  
Rafaela Mostallino ◽  
Franca Piras ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell ◽  
In Vitro Study ◽  
Dependent Manner ◽  
Novel Psychoactive Substances ◽  
Psychoactive Substances ◽  
Concentration Dependent Manner ◽  
Mechanisms Of Toxicity ◽  
Neuronal Cell Lines

Novel psychoactive substances (NPS) are synthetic substances belonging to diverse groups, designed to mimic the effects of scheduled drugs, resulting in altered toxicity and potency. Up to now, information available on the pharmacology and toxicology of these new substances is very limited, posing a considerable challenge for prevention and treatment. The present in vitro study investigated the possible mechanisms of toxicity of two emerging NPS (i) 4′-methyl-alpha-pyrrolidinoexanophenone (3,4-MDPHP), a synthetic cathinone, and (ii) 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA), a phenethylamine. In addition, to apply our model to the class of synthetic opioids, we evaluated the toxicity of fentanyl, as a reference compound for this group of frequently abused substances. To this aim, the in vitro toxic effects of these three compounds were evaluated in dopaminergic-differentiated SH-SY5Y cells. Following 24 h of exposure, all compounds induced a loss of viability, and oxidative stress in a concentration-dependent manner. 2-Cl-4,5-MDMA activates apoptotic processes, while 3,4-MDPHP elicits cell death by necrosis. Fentanyl triggers cell death through both mechanisms. Increased expression levels of pro-apoptotic Bax and caspase 3 activity were observed following 2-Cl-4,5-MDMA and fentanyl, but not 3,4-MDPHP exposure, confirming the different modes of cell death.

scholarly journals Self-Targeting of Carbon Dots into the Cell Nucleus: Diverse Mechanisms of Toxicity in NIH/3T3 and L929 Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5608
Author(s):  
Markéta Havrdová ◽  
Iztok Urbančič ◽  
Kateřina Bartoň Tománková ◽  
Lukáš Malina ◽  
Janez Štrancar ◽  
...  
Keyword(s):  
Dna Damage ◽  
Carbon Dots ◽  
L929 Cell ◽  
Fluorescent Properties ◽  
Cell Cycle Profile ◽  
Mechanisms Of Toxicity ◽  
3T3 Fibroblasts ◽  
Nih 3T3 ◽  
Positively Charged ◽  
Endocytic Pathways

It is important to understand the nanomaterials intracellular trafficking and distribution and investigate their targeting into the nuclear area in the living cells. In our previous study, we firstly observed penetration of nonmodified positively charged carbon dots decorated with quaternary ammonium groups (QCDs) into the nucleus of mouse NIH/3T3 fibroblasts. Thus, in this work, we focused on deeper study of QCDs distribution inside two healthy mouse NIH/3T3 and L929 cell lines by fluorescence microspectroscopy and performed a comprehensive cytotoxic and DNA damage measurements. Real-time penetration of QCDs across the plasma cell membrane was recorded, concentration dependent uptake was determined and endocytic pathways were characterized. We found out that the QCDs concentration of 200 µg/mL is close to saturation and subsequently, NIH/3T3 had a different cell cycle profile, however, no significant changes in viability (not even in the case with QCDs in the nuclei) and DNA damage. In the case of L929, the presence of QCDs in the nucleus evoked a cellular death. Intranuclear environment of NIH/3T3 cells affected fluorescent properties of QCDs and evoked fluorescence blue shifts. Studying the intracellular interactions with CDs is essential for development of future applications such as DNA sensing, because CDs as DNA probes have not yet been developed.

The Development and Evaluation of In Vitro Tests by the FRAME Alternatives Laboratory

1995 ◽  
Vol 23 (1) ◽  
pp. 75-90
Author(s):  
Richard H. Clothier ◽  
Karen A. Atkinson ◽  
Michael J. Garle ◽  
Rachel K. Ward ◽  
Angela Willshaw
Keyword(s):  
Research Programme ◽  
Neutral Red ◽  
In Vitro Cytotoxicity ◽  
In Vitro Tests ◽  
Dermal Toxicity ◽  
Mechanisms Of Toxicity ◽  
The Us ◽  
Detergent Association ◽  
Assay Methods

This review outlines the work which has been conducted in the FRAME Alternatives Laboratory during the first ten years of the FRAME Research Programme. A number of in vitro tests, including the kenacid blue, neutral red release and fluorescein leakage assay methods, have been evaluated and have subsequently been included in validation schemes organised by the US Soap and Detergent Association, the US Cosmetic, Toiletry and Fragrance Association, the European Commission and the European Cosmetic, Toiletry and Perfumery Association, as well as in the Scandinavian multicentre evaluation of in vitro cytotoxicity testing scheme. More recently, research has been undertaken in the areas of phototoxicity, immunotoxicity, dermal toxicity and intercellular communication, in addition to investigations into fundamental mechanisms of toxicity.

scholarly journals Comparative Proteomic Analysis of Carbonylated Proteins from the Striatum and Cortex of Pesticide-Treated Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Christina Coughlan ◽  
Douglas I. Walker ◽  
Kelly M. Lohr ◽  
Jason R. Richardson ◽  
Laura M. Saba ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pesticide Exposure ◽  
Epidemiological Studies ◽  
Cytoskeletal Proteins ◽  
Synaptic Function ◽  
Behavioral Alterations ◽  
Mechanisms Of Toxicity ◽  
Kegg Pathways ◽  
Increased Risk ◽  
Proteomic Analyses

Epidemiological studies indicate exposures to the herbicide paraquat (PQ) and fungicide maneb (MB) are associated with increased risk of Parkinson’s disease (PD). Oxidative stress appears to be a premier mechanism that underlies damage to the nigrostriatal dopamine system in PD and pesticide exposure. Enhanced oxidative stress leads to lipid peroxidation and production of reactive aldehydes; therefore, we conducted proteomic analyses to identify carbonylated proteins in the striatum and cortex of pesticide-treated mice in order to elucidate possible mechanisms of toxicity. Male C57BL/6J mice were treated biweekly for 6 weeks with saline, PQ (10 mg/kg), MB (30 mg/kg), or the combination of PQ and MB (PQMB). Treatments resulted in significant behavioral alterations in all treated mice and depleted striatal dopamine in PQMB mice. Distinct differences in 4-hydroxynonenal-modified proteins were observed in the striatum and cortex. Proteomic analyses identified carbonylated proteins and peptides from the cortex and striatum, and pathway analyses revealed significant enrichment in a variety of KEGG pathways. Further analysis showed enrichment in proteins of the actin cytoskeleton in treated samples, but not in saline controls. These data indicate that treatment-related effects on cytoskeletal proteins could alter proper synaptic function, thereby resulting in impaired neuronal function and even neurodegeneration.

scholarly journals Diagnosis, Prevention, Treatment and Surveillance of Anthracycline-Induced Cardiovascular Toxicity in Pediatric Cancer Survivors

Hearts ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 45-60
Author(s):  
Valerie Curren ◽  
Niti Dham ◽  
Christopher Spurney
Keyword(s):  
Pediatric Cancer ◽  
Systolic Function ◽  
Treatment Strategies ◽  
Significant Risk ◽  
Imaging Biomarkers ◽  
Cancer Therapies ◽  
Cardiovascular Toxicity ◽  
Treatment Protocols ◽  
Mechanisms Of Toxicity ◽  
Pediatric Cancer Survivors

Advances in pediatric cancer therapies have dramatically improved the likelihood of survival. As survivors are aging, however, we are now understanding that treatment carries a significant risk of cardiovascular toxicity, which can develop immediately, or even many years after completing therapy. Anthracycline derivates are some of the most commonly used agents in pediatric oncology treatment protocols, which have a dose-dependent correlation with the development of cardiac toxicity. As we learn more about the mechanisms of toxicity, we are developing prevention strategies, including improvements in surveillance, to improve early diagnosis of heart disease. Current survivorship surveillance protocols often include screening echocardiograms to evaluate systolic function by measuring the ejection fraction or fractional shortening. However, these measurements alone are not enough to capture early myocardial changes. The use of additional imaging biomarkers, serum biomarkers, electrocardiograms, as well as cholesterol and blood pressure screening, are key to the early detection of cardiomyopathy and cardiovascular disease. Medical treatment strategies are the same as those used for heart failure from other causes, but earlier recognition and implementation can lead to improved long term outcomes.

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