Assessing neurological and cardiovascular effects caused by pharmaceuticals in river water: Insights from Daphnia magna and Danio rerio embryos.

Pharmaceutical residues in surface waters are an emerging environmental and public health issue, yet their biological impacts on aquatic life remain poorly understood. This study presents a cost-effective bioanalytical framework using Daphnia magna juveniles and zebrafish (Danio rerio) embryos to evaluate neurotoxic and cardiotoxic effects of pharmaceutical mixtures in rivers downstream of wastewater treatment plant (WWTP) effluents. Water samples from three rivers in north-eastern Spain (Besòs, Llobregat, and Onyar) were concentrated up to 5- and 20-fold using solid-phase extraction.

Ultra-sensitive UHPLC-MS/MS method for simultaneous quantification of 31 neurochemicals in zebrafish larvae and brain.

The precise determination of neurotransmitters and their metabolites in biological matrices is critical for research on neurological disorders, including those originated by the exposure to neurotoxic chemicals. This study presents an optimized liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for 31 neurochemicals, including neurotransmitters, their metabolites and precursors. The method is aimed at achieving lower limits of detection (LOD) and quantification (LOQ) compared to those currently available, while simultaneously expanding the number of compounds analyzed.

N-Acetylcysteine-Amide Protects Against Acute Acrylamide Neurotoxicity in Adult Zebrafish.

Acrylamide (ACR) is a potent neurotoxicant that disrupts cellular redox homeostasis by depleting reduced glutathione (GSH) and inducing oxidative stress. Despite its well-characterized mechanism, no effective treatments for ACR-induced neurotoxicity currently exist. This study evaluates the therapeutic efficacy of N-acetylcysteine-amide (AD4), a blood-brain barrier (BBB)-permeable derivative of N-acetylcysteine, in a novel severe acute ACR neurotoxicity model in adult zebrafish.

Efficient Small-Molecule Reversal Agents for Anticoagulant Fondaparinux.

Fondaparinux is a highly anionic synthetic heparinoid pentasaccharide used as an anticoagulant for specific clinical conditions and surgeries. As a non-natural small-molecule drug, it presents pharmacokinetic and pharmacodynamic advantages, as well as high stability and low immunogenicity, when compared with different forms of heparin. However, its broader usage is hampered by different factors like price, existence of alternative anticoagulants, or, specifically in this case, the lack of an effective antidote that is highly recommendable for avoiding uncontrolled bleeding.

Motor and Non-Motor Effects of Acute MPTP in Adult Zebrafish: Insights into Parkinson's Disease.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor and non-motor symptoms. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been extensively used in different animal species to develop chemical models of PD. This study aimed to evaluate the effects of acute exposure to MPTP (3 × 150 mg/kg, intraperitoneally) on adult zebrafish by assessing the neurochemical, transcriptional, and motor changes associated with PD pathogenesis.

Fluoroquinolone and sulfonamide antibiotics (single and mixtures) impair the motor function of zebrafish larvae at environmentally relevant concentrations.

The occurrence of antibiotics in freshwater is a global concern, with evidence pointing to potential neurotoxic effects after prolonged exposure. However, data on their impact on behavior, particularly at environmentally relevant concentrations, remain limited. This study examined the motor function of zebrafish larvae exposed to single and mixture of antibiotics from the sulfonamide and fluoroquinolone classes.

Zebra_K, a kinematic analysis automated platform for assessing sensitivity, habituation and prepulse inhibition of the acoustic startle response in adult zebrafish.

The acoustic startle response (ASR) is leaded by a sudden and intense acoustic stimulus. ASR has several forms of plasticity, including habituation and sensorimotor gating. Although ASR and its plasticity have been intensively studied in zebrafish (Danio rerio) larvae, information in adult zebrafish is still very scarce.

Analyzing the neurotoxic effects of anatoxin-a and saxitoxin in zebrafish larvae.

Global warming due to climate change, as well as freshwater eutrophication caused by anthropogenic activities are responsible, among other factors, for an increasing occurrence of harmful algal blooms (HABs) in aquatic systems. These can lead to the generation of cyanotoxins, secondary metabolites coming from cyanobacteria, producing adverse effects in living organisms including death. This research aims to study the effects that two neurotoxins, anatoxin-a (ATX-a) and saxitoxin (STX), have on living organisms.

Analyzing the Effects of Age, Time of Day, and Experiment on the Basal Locomotor Activity and Light-Off Visual Motor Response Assays in Zebrafish Larvae.

The recent availability of commercial platforms for behavioral analyses in zebrafish larvae based on video-tracking technologies has exponentially increased the number of studies analyzing different behaviors in this model organism to assess neurotoxicity. Among the most commonly used assays in zebrafish larvae are basal locomotor activity (BLA) and visual motor responses (VMRs). However, the effect of different intrinsic and extrinsic factors that can significantly alter the outcome of these assays is still not well understood.

Cardiac and neurobehavioral impairments in three phylogenetically distant aquatic model organisms exposed to environmentally relevant concentrations of boscalid.

Boscalid (2-Chloro-N-(4'-chlorobiphenyl-2-yl) nicotinamide), a pyridine carboxamide fungicide, is an inhibitor of the complex II of the respiration chain in fungal mitochondria. As boscalid is only moderately toxic for aquatic organisms (LC > 1-10 mg/L), current environmental levels of this compound in aquatic ecosystems, in the range of ng/L-μg/L, are considered safe for aquatic organisms. In this study, we have exposed zebrafish (Danio rerio), Japanese medaka (Oryzias latipes) and Daphnia magna to a range of concentrations of boscalid (1-1000 μg/L) for 24 h, and the effects on heart rate (HR), basal locomotor activity (BLA), visual motor response (VMR), startle response (SR), and habituation (HB) to a series of vibrational or light stimuli have been evaluated.

Short-term exposure to environmental levels of nicotine and cotinine impairs visual motor response in zebrafish larvae through a similar mode of action: Exploring the potential role of zebrafish α7 nAChR.

The current view is that environmental levels of nicotine and cotinine, commonly in the ng/L range, are safe for aquatic organisms. In this study, 7 days post-fertilization zebrafish embryos have been exposed for 24 h to a range of environmental concentrations of nicotine (2.0 ng/L-2.

Analysis of sleep/wake cycles in zebrafish larvae.

Zebrafish larvae are a model organism increasingly used in the study of the effect of neuroactive chemicals on vertebrate sleep/wake cycles. Sleep disturbances have a negative impact on mood, cognition and overall health. Here we present a protocol to assess over 24 h sleep/wake cycles in zebrafish larvae subjected to 12 h light/dark periods in 48-well plates, using video-tracking technologies.

Neurotoxicity Assessment in Adult Danio rerio using a Battery of Behavioral Tests in a Single Tank.

The presence of neuropathological effects proved to be, for many years, the main endpoint for assessing the neurotoxicity of a chemical substance. However, in the last 50 years, the effects of chemicals on the behavior of model species have been actively investigated. Progressively, behavioral endpoints were incorporated into neurotoxicological screening protocols, and these functional outcomes are now routinely used to identify and determine the potential neurotoxicity of chemicals.

Environmental concentrations of tire rubber-derived 6PPD-quinone alter CNS function in zebrafish larvae.

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone) is a degradation product of 6PPD, an antioxidant widely used in rubber tires. 6PPD-quinone enters aquatic ecosystems through urban stormwater runoff and has been identified as the chemical behind the urban runoff mortality syndrome in coho salmon. However, the available data suggest that the acute effects of 6PPD-quinone are restricted to a few salmonid species and that the environmental levels of this chemical should be safe for most fish.

Heart rate and behavioral responses in three phylogenetically distant aquatic model organisms exposed to environmental concentrations of carbaryl and fenitrothion.

Carbaryl and fenitrothion are two insecticides sharing a common mode of action, the inhibition of the acetylcholinesterase (AChE) activity. Their use is now regulated or banned in different countries, and the environmental levels of both compounds in aquatic ecosystems have decreased to the range of pg/L to ng/L. As these concentrations are below the non-observed-adverse-effect-concentrations (NOAEC) for AChE inhibition reported for both compounds in aquatic organisms, there is a general agreement that the current levels of these two chemicals are safe for aquatic organisms.

Developmental exposure to sertraline impaired zebrafish behavioral and neurochemical profiles.

The number of people suffering from mental health problems is rising, with anxiety and depression now the most commonly diagnosed psychiatric conditions. Selective serotonin reuptake inhibitors (SSRIs) are one of the most prescribed pharmaceuticals to treat these conditions, which has led to their common detection in many aquatic ecosystems. As the monoaminergic system shows a high degree of structural conservation across diverse animal phyla, a reasonable assumption is that the environmental levels of SSRIs in surface water can lead to adverse effects on fish and other aquatic wildlife.

Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissues.

Adrenoceptors are G protein-coupled receptors involved in a large variety of physiological processes, also under pathological conditions. This is due in large part to their ubiquitous expression in the body exerting numerous essential functions. Therefore, the possibility to control their activity with high spatial and temporal precision would constitute a valuable research tool.

A Photoswitchable Ligand Targeting the β -Adrenoceptor Enables Light-Control of the Cardiac Rhythm.

Catecholamine-triggered β-adrenoceptor (β-AR) signaling is essential for the correct functioning of the heart. Although both β - and β -AR subtypes are expressed in cardiomyocytes, drugs selectively targeting β -AR have proven this receptor as the main target for the therapeutic effects of beta blockers in the heart. Here, we report a new strategy for the light-control of β -AR activation by means of photoswitchable drugs with a high level of β -/β -AR selectivity.

Environmental levels of carbaryl impair zebrafish larvae behaviour: The potential role of ADRA2B and HTR2B.

The insecticide carbaryl is commonly found in indirectly exposed freshwater ecosystems at low concentrations considered safe for fish communities. In this study, we showed that after only 24 h of exposure to environmental concentrations of carbaryl (0.066-660 ng/L), zebrafish larvae exhibit impairments in essential behaviours.

A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure.

Hyperthermia is a common confounding factor for assessing the neurotoxic effects of methamphetamine (METH) in mammalian models. The development of new models of methamphetamine neurotoxicity using vertebrate poikilothermic animals should allow to overcome this problem. The aim of the present study was to develop a zebrafish model of neurotoxicity by binge-like methamphetamine exposure.