Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
Results
Showing 1 to 15 of 15 for “"mitochondrial toxicity"”.
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Statin-induced muscle mitochondrial toxicity
… no convenient and reliable marker of SIM, but mitochondrial dysfunction has been implicated. We sought to investigate the effect of statins on mitochondrial DNA (mtDNA) levels in order to gain information on the mechanism of SIM and to explore the possibility of utilizing changing mtDNA levels …
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Using Heterogeneous Information Sources for Understanding and Predicting Biological Effects of Compounds
… Receptor 1 family. The final chapter, “Mitochondrial Toxicity Prediction using Cell Painting Assay on a PROTACs dataset”, explored the successful profiling of a novel data modality (PROTACs) with the Cell Painting assay and evaluated whether this profiling can be used in the …
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Pharmacogenetics of stavundine : role of genetic variation in mitochondrial DNA and polymerase gamma among adult Malawian HIV/AIDS patients
… the genetic correlates for drugs associated with mitochondrial toxicity that are used as part of HIV therapy, especially nucleoside reverse transcriptase inhibitors (NRTIs). Toxicity from NRTIs manifests through metabolic diseases such as peripheral neuropathy, lipodystrophy, lactic acidosis and …
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Synthesis and Design of ClpP Activators as Novel Antibiotics
… Explore their potential as antibiotics through mitochondrial toxicity tests, glucose/galactose assays, and biophysical measurements related to metabolism and clearance, including thermal shift and surface plasmon resonance assays. Results. Synthesized and tested 33 novel compounds, comprising a …
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Development of in silico models to support repeat dose safety assessment of cosmetic ingredients to humans
… increase in research into the use of alternative toxicity testing methods, such as in vitro, in chemico and in silico. Whilst there are a number of alternative techniques that may be employed, no one method can be used in isolation as a full replacement for an in vivo test. Therefore, the Adverse …
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Accurate Uncertainty Quantification and Explainable Artificial Intelligence in Machine Learning Models for Toxicological Risk Assessment
… mechanistically driven structural alerts for mitochondrial toxicity. Structural alerts are constructed using a maximum common substructure algorithm developed by Wedlake et al. (2020) and their mechanisms are verified by literature review. The alerts performed well on external validation when …
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Mechanism of TNF-α cytotoxicity in a leukemia virus transformation model
… sensitivity to TNF-α. The differential cytotoxicity was observed when cells were treated with TNF-α, for 18 hr, at 0 to 100 units/ml, at 37°C. The mechanism of this differential cytotoxicity was further investigated. Thus, TNF-R levels on the cell surface were found to be not correlated with …
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UNDERSTANDING CONDITIONAL MODES OF ACTIONS IN CHEMICAL-INDUCED TOXICITY USING RULE MODELS
… shifting efforts toward alternative methods for toxicity assessment is essential. However, slow regulatory acceptance of new approaches is governed by knowledge gaps in toxicity modes of action. In this thesis, I describe these challenges and the use of in vitro screening as an alternative of …
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Using Cell Painting and Chemical Data for Small-molecule Bioactivity and Toxicity Prediction
… the mechanism of action of a compound, its toxicity profile, and many other biological effects. Traditional approaches in drug discovery primarily rely on chemical structure fingerprints, which do not capture biological responses to compounds. By integrating cell morphology data, models …
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The role of mitochondrial transporters in human physiology and adverse drug effects
… prescribed medications often cause off-target mitochondrial dysfunction, but the underlying molecular mechanisms are largely unknown. Mitochondrial transport proteins form a significant class of potential off-targets that remain largely unexplored. The main aim of this thesis is to evaluate the …
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Computer modelling of metabolic adaptions during mitochondrial dysfunction and machine learning to predict novel mitochondrial disease genes
… This thesis investigates two main causes of mitochondrial dysfunction: mitochondrial toxicity arising from side-effects of drugs; and mitochondrial diseases arising from defects in nuclear-encoded genes. Novel chemical entities being developed as drug leads are screened for cellular toxicity …
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Anti-hyperlipidemic activities of Ilex latifolia and other selected herbs
… and AML-12 hepatocytes. Ilex latifolia effect on mitochondrial metabolism, and glucose uptake was assayed in HepG2 and AML-12 hepatocytes. Chapter I is an introduction to hyperlipidemia, its types, causes, and treatment. A review of the literature relating to Ilex latifolia and other herbs and …
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Optimising linezolid use for drug-resistant tuberculosis: pharmacokinetics, toxicity, and resistance
… The major drawback of linezolid is dose-related mitochondrial toxicity that may be treatment limiting. The incidence and risk factors for linezolid adverse events have not been systematically studied in TB programmes, particularly in populations from sub-Saharan Africa with high rates of HIV …
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Discovery of small-molecule natural products that target cellular bioenergetics
… enhance the effectiveness of current therapies. Mitochondrial oxidative phosphorylation inhibitors in botanical dietary supplements (BDS) possess a potential health hazard which should be identified and appropriately regulated. Chapter one briefly reviews the molecular-targeted natural product …
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5 ns Electric pulses evoke longer-lived calcium responses in adrenal chromaffin cells than the physiological stimulus: an experimental and computational study
… influx through VGCCs, and a disruption of mitochondrial membrane potential has been shown to delay calcium clearance, our first aim was to explore whether 5 ns pulses affect mitochondrial membrane potential using fluorescent mitochondrial membrane potential dyes. Control experiments …