Publications by authors named "M Hetheridge"
With the US Environment Protection Agency reducing requests for (and funding of) mammalian studies alongside the proposed elimination of requests by 2035, there is an urgent need for fully validated New Approach Methods (NAMs) to fill the resultant gap for safety assessment of agrochemicals. One promising NAM for assessing the potential for human prenatal developmental toxicity potential is the Zebrafish Embryo Developmental Toxicity Assessment, a bioassay that has been used by the pharmaceutical industry for more than a decade in early-stage drug safety assessment. Despite its promise, little data has been generated to assess the validity of ZEDTA for assessing Developmental and Reproductive Toxicity of new agrochemical products.
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- Rising global temperatures due to climate change may worsen the toxic effects of pollutants like pharmaceuticals on wildlife, particularly fish, which are sensitive to environmental temperature changes.
- The study used genetically modified zebrafish to investigate how higher temperatures (increased by 2-5 °C) amplify oxidative stress caused by drugs such as paracetamol, diclofenac, and doxorubicin.
- Findings suggest that risk assessments for chemical toxicity in aquatic life should take into account the impact of temperature, as elevated heat can increase both drug absorption and oxidative stress in fish, posing risks for their health and the environment.
Article Synopsis
- - Antidepressants, particularly the tricyclic drug amitriptyline (AMI), are widely prescribed, raising concerns about their effects on non-target aquatic organisms like fish due to potential environmental exposure.
- - A study using zebrafish revealed that AMI accumulates in their bodies, converts to an active metabolite, and impacts gene expression related to serotonin transport even at low, environmentally relevant concentrations.
- - While higher concentrations of AMI affected fish behavior (like increased hatch rates and decreased movement), the overall low risk to fish populations may be underestimated due to factors like the ongoing increase in prescription rates and the presence of other drugs acting similarly.
The clinical heterogeneity of heart failure has challenged our understanding of the underlying genetic mechanisms of this disease. In this respect, large-scale patient DNA sequencing studies have become an invaluable strategy for identifying potential genetic contributing factors. The complex aetiology of heart failure, however, also means that models are vital to understand the links between genetic perturbations and functional impacts as part of the process for validating potential new drug targets.
View Article and Find Full Text PDFBackground And Purpose: Functional brain imaging using genetically encoded Ca sensors in larval zebrafish is being developed for studying seizures and epilepsy as a more ethical alternative to rodent models. Despite this, few data have been generated on pharmacological mechanisms of action other than GABA antagonism. Assessing larval responsiveness across multiple mechanisms is vital to test the translational power of this approach, as well as assessing its validity for detecting unwanted drug-induced seizures and testing antiepileptic drug efficacy.
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