Search Results (128)

Paroxetine, a selective serotonin reuptake inhibitor commonly used to treat various psychiatric disorders, may adversely affect female reproductive function. Although apigenin has been shown to ameliorate reproductive abnormalities and ovarian dysfunction, its effect on paroxetine-induced reproductive toxicity in females remains unclear. Therefore, this study investigated the potential protective effects of apigenin against paroxetine-induced reproductive alterations in female rats. Female rats with regular estrous cycles were randomly assigned to four groups (n = 9 per group): control, apigenin, paroxetine, and paroxetine + apigenin. The rats received saline, apigenin (20 mg/kg), paroxetine (10 mg/kg), or their combination by oral gavage once daily for about 29 consecutive days. Compared with paroxetine treatment alone, apigenin co-administration restored decreased serum anti-Müllerian hormone (AMH) levels, enhanced PAS reactivity in the zona pellucida, reduced ovarian iNOS immunoreactivity, increased follicle and corpus luteum numbers, and increased ovarian VEGF immunoreactivity. However, apigenin administration alone was associated with reduced testosterone levels and alterations in certain ovarian and uterine histological features in female rats. In conclusion, the findings suggest that apigenin may ameliorate paroxetine-induced reproductive alterations in female rats by modulating AMH levels, follicle and corpus luteum numbers, and ovarian histochemical and molecular parameters. Full article

The rising global demand for lithium has led to substantial accumulation of lithium slag, a by-product of lithium carbonate production and a potential environmental contaminant. Leachates from this material contain various metal elements and may pose risks to ecosystems and organismal health. However, research on its neurotoxicity and underlying mechanisms remains limited. In this study, zebrafish embryos at 6 h post-fertilisation were exposed to varying concentrations of lithium slag leachate for 7 days. The leachate contained multiple metal ions (Li, Fe, Mn, Ni, Zn, As, Cr, Cu, Hg, Cd, Pb, etc.). Following exposure, significant metal accumulation was observed in larvae, accompanied by developmental malformations (yolk sac oedema, cardiac haemorrhage, and uninflated swim bladders). Behavioural assessment revealed reduced swimming distance and velocity, along with disrupted circadian rhythms. Biochemical analyses showed elevated Reactive oxygen species (ROS), Superoxide dismutase (SOD), Catalase (CAT), and Malondialdehyde (MDA), alongside decreased Glutathione (GSH), indicating oxidative stress. Transcriptomic analysis confirmed downregulation of core circadian genes. Neurotransmitter assays revealed decreased acetylcholine (Ach), noradrenaline (NE), and dopamine (DA), with increased gamma-aminobutyric acid (GABA) and serotonin (5-HT). These findings demonstrate that lithium slag leachate induces oxidative stress, circadian disruption, and neurobehavioural toxicity in zebrafish, providing important evidence for environmental risk assessment. Full article

The accumulated ammonia within the recirculating aquaculture systems threaten fish health, while little is known about the influences during early fish ontogeny. Using larval and juvenile yellow catfish (Pelteobagrus fulvidraco) as a model, a comprehensive experiment exposing fish to varying total ammonia nitrogen concentrations (0, 10, 20 mg/L for larvae; 0, 25, 125 mg/L for juveniles) was conducted to evaluate the effects on gill transcriptome and microbiota along with the serotonergic regulation. First, the serotonin (5-HT) signal, which controls oxygen chemoreception and ventilation, was mainly detected in the surface of the body of the larvae, and then shifted to gill filaments of juveniles, showing a transition from cutaneous to branchial respiration. Both larval and juvenile yellow catfish exhibited reduced survival, damaged gill structure, and elevated 5-HT expression after ammonia exposure, as well as upregulated tph1b, slc6a4b, scgn and lama5 expression with the increased ammonia concentration, indicating the effects on respiratory function via serotonergic regulation. Further transcriptome analysis was conducted in juveniles to identify the differentially expressed genes (DEGs) and thus, to illustrate more detailed responses after ammonia exposure; KEGG enrichment analysis of DEGs indicated the coping strategy shifted from metabolic buffering to metabolic elimination via glutamine synthesis with the increased ammonia level. The qRT-PCR experiment also identified the increased expression of genes involved in the urea cycle—such as ass1, asl and glula—with the increased ammonia level. Considering the potential contributary role of microbiome to gill health, 16S sequencing was conducted on the gill in the control and the 125 mg/L ammonia-exposed group. Ammonia exposure at 125 mg/L induced significant variation in Simpson index and a marked decline in β diversity. Notably, the abundance of opportunistic pathogens such as Pseudomonadota increased, while the abundance of Deinococcota and Deinococcus—which were renowned for exceptional stress resistance capacity—decreased after ammonia exposure. Thus ammonia exposure disrupts the transcriptomic and microecological balance within gill mucosa, which may elevate the risk of pathogenic infection. Overall, our study provided the first evidence of serotonergic regulation on early fish respiration during ammonia exposure, and also offered new theoretical insights into the involvement of microorganisms in ammonia toxicity. Full article

Parkinson’s disease (PD) is one of the most prevalent and extensively studied neurodegenerative conditions. One of its most challenging clinical manifestations is the emergence of dyskinesias, characterized by involuntary movements that significantly impair patients’ quality of life. Meanwhile, boron, as a trace element, and boron-containing compounds have emerged as active modulators of neurotransmitter systems. To evaluate the effect of aryl-boroxazolidones on parkinsonism, the in vitro neurotoxicity of three boroxazolidones was assessed, along with the effects of two of them in mice with parkinsonism induced by MPTP administration. Two novel compounds demonstrated a limitation of parkinsonism, whereas risperidone reduced the beneficial effect of the tested boroxazolidones. The three boroxazolidones did not induce toxicity in neurons or glial cells at concentrations up to 100 µM. In silico analyses support the ability of BCC to act as ligands of dopamine and serotonin receptors. Taken together, these results suggest that the tested boroxazolidones are promising candidate agents, warranting further exploration for the treatment of PD. Full article

Background/Objectives: Plant-based supplements are widely used for the management of anxiety, depression, and insomnia. Despite their over-the-counter availability and perceived safety, these products may pose relevant pharmacological and toxicological risks. This narrative review critically evaluates clinical evidence on commonly used herbal preparations, with particular emphasis on herb–drug interactions, adverse effects, and issues related to product adulteration. Methods: Major scientific databases (PubMed, Scopus, and Web of Science) were searched to identify clinical studies evaluating plant-based supplements for mental health and sleep disorders. Data on study design, dosage, efficacy, and adverse events were analyzed, together with regulatory information and reports of product adulteration and quality concerns. Results: Herbal supplements such as Hypericum perforatum, Passiflora incarnata, Valeriana officinalis, Piper methysticum, Withania somnifera, Crocus sativus, and Curcuma longa demonstrated anxiolytic, antidepressant, and sedative effects in clinical studies, with improvements in mood, stress levels, and sleep quality. Proposed mechanisms include modulation of monoaminergic and GABAergic pathways, serotonergic activity, regulation of the hypothalamic–pituitary–adrenal axis, and anti-inflammatory effects. However, clinically relevant risks were identified, including cytochrome P450–mediated drug interactions, excessive sedation, serotonin syndrome, and toxic effects associated with adulterated products, such as hepatotoxicity, cardiovascular events, and neurological disturbances. Conclusions: While plant-based supplements may provide clinically meaningful benefits for anxiety, depression, and insomnia, their use requires careful clinical monitoring due to potential pharmacokinetic and pharmacodynamic interactions and safety concerns. Increased awareness of herb–drug interactions and stricter quality control are essential to optimize therapeutic outcomes and minimize harm. Full article

Depression remains a major global health challenge, with a significant proportion of patients failing to respond to conventional antidepressants. This study aimed to evaluate the potential antidepressant effects and toxicological profile of a novel tetrodotoxin (TTX) oral film formulation in a mouse model of chronic unpredictable mild stress (CUMS). Male C57BL/6J mice were subjected to CUMS and treated daily with TTX oral film at doses of 10, 20, and 40 μg/kg, with fluoxetine (18 mg/kg) serving as a positive control. Behavioral assessments, including sucrose preference test, open field test, forced swimming test, elevated plus maze, and novel object recognition, demonstrated that TTX oral film administration alleviated depression- and anxiety-like behaviors and improved cognitive function. Furthermore, TTX oral film treatment restored hippocampal serotonin levels, which were depleted in CUMS mice, and showed no adverse effects on organ indexes after long-term use. Toxicological evaluation through acute toxicity testing revealed an oral LD₅₀ of 919 μg/kg, indicating a substantially improved safety profile compared to pure TTX and a wide therapeutic window. These findings suggest that the TTX oral film possesses significant antidepressant activity with favorable toxicological properties, supporting its potential as a novel and safe treatment for depression. Full article

Microplastics (MPs) and antibiotics have emerged as contaminants of global concern, posing potential threats to ecosystem security and organismal health. To investigate the individual and combined toxicity of microplastics (PS-MPs) and sulfamethoxazole (SMX), we conducted a 120 h acute exposure experiment using embryo–larval zebrafish as a toxicological model. Our findings demonstrate that both PS-MPs and SMX can induce neurodevelopmental toxicity in embryo–larval zebrafish during embryonic development. Notably, PS-MPs and SMX exerted a significant synergistic effect. PS-MPs 1 µm in diameter were restricted to the chorion surface of pre-hatching zebrafish, whereas post-hatching, PS-MPs accumulated mainly in the gut and gills, with accumulation levels increasing progressively with exposure duration. Individual exposure to PS-MPs or SMX reduced spontaneous locomotion, decreased heart rate, and shortened body length in embryo–larval zebrafish. In addition to exacerbating these effects, coexposure further increased the incidence of malformations such as pericardial effusion and spinal curvature. PS-MPs and SMX significantly decreased the levels of dopamine (DA), serotonin (5-HT), and γ-aminobutyric acid (GABA) in zebrafish while also suppressing acetylcholinesterase (AChE) activity and increasing acetylcholine (ACh) levels. Moreover, upon coexposure at high concentrations, PS-MPs and SMX acted synergistically to reduce the levels of DA and GABA. The downregulation of key neurodevelopmental genes (elavl3, gap43, and syn2a) and related neurotransmitter pathway genes indicates that PS-MPs and SMX impaired structural development and functional regulation of the nervous system. An integrated biomarker response (IBR) index confirmed that PS-MPs and SMX significantly enhanced developmental neurotoxicity during early neurodevelopment in embryo–larval zebrafish through synergistic effects. Our study provides critical toxicological evidence for the scientific assessment of the ecological risks posed by microplastic–antibiotic cocontamination. Full article

Fluoxetine (FLX) is an antidepressant pertaining to the class of selective serotonin reuptake inhibitors. FLX use has increased in the past decade culminating in its discharge to surface waters. Owing to the limited knowledge about the toxicity of this drug to aquatic biota, this study aimed to evaluate potential toxic effects of FLX on green algae Chlorella vulgaris, cyanobacteria Microcystis novacekii, marine bacteria Aliivibrio fischeri, and mollusk Biomphalaria glabrata. Assays with C. vulgaris and M. novacekii followed OECD protocol 201 (2011) and NBR 12648 standard (2018), respectively. The assay with A. fischeri was carried out according to ISO/OIN 11348-3 (2007). Toxicity assays with B. glabrata were performed by exposing these organisms (newborn and embryos) in 24-well culture plates for 3 and 7 days, respectively. All test-organisms were exposed to at least 6 different concentrations of FLX, ranging from 0.1 to 20,000 µg/L, in triplicates. Effect concentrations (EC50) obtained for these assays showed that FLX is more toxic to M. novacekii (10.71 ± 1.67 µg/L), followed by C. vulgaris (13.01 ± 2.01 µg/L) and A. fischeri (3140 ± 1050 µg/L). Regarding B. glabrata, the 50% lethal concentration for newborns was 1770 ± 260 µg/L, while for embryos it was equivalent to 34.98 ± 3.66 µg/L. Considering recent reports of FLX occurrence in environmental matrices in the µg/L range, results reported in this study and the toxicity classification criteria by the Globally Harmonized System, FLX poses high risk to aquatic environments, its biodiversity, and ecosystems. Therefore, measures must be taken to prevent the disposal of waste containing FLX into the environment, especially in region lacking basic sanitation infrastructure. Full article

The aim of this study was to evaluate the impact of fluoxetine, a widely used selective serotonin reuptake inhibitor, on two aquatic plants: Lemna minor and Spirodela polyrhiza. Additionally, the effect of exogenous serotonin on the level of fluoxetine-induced stress in duckweed will be studied. Increasing presence of antidepressants in surface waters poses ecological risks, and the duckweed species are ideal model organisms for ecotoxicological studies due to their rapid growth and ability to accumulate pollutants. For 14 days, plants were exposed to fluoxetine (0.001–150 mg L⁻¹), followed by a recovery phase in a drug-free medium or a medium supplemented with exogenous serotonin. We analysed morphological/physiological parameters (frond length and area, fresh and dry mass, hydration, stomatal size), the activity of antioxidant enzymes (catalase, ascorbate peroxidase, superoxide dismutase), cell viability, and the level of heat-shock proteins. The plants’ ability to remove fluoxetine from the medium was also assessed. High fluoxetine concentrations (50–150 mg L⁻¹) significantly reduced fresh mass (by 63–98% in L. minor and 56–97% in S. polyrhiza), frond area (by 21–48% in L. minor and 11–25% in S. polyrhiza), and cell viability (by 36–94% in L. minor and 49–94% in S. polyrhiza), and induced oxidative stress. Despite this, both species showed high regeneration potential after the stressor’s removal. Serotonin supplementation did not affect morphology but increased antioxidant enzyme activity, improved cell viability, and elevated heat-shock proteins levels. Crucially, serotonin significantly increased the efficiency of fluoxetine removal. The data can provide a basis for predicting fluoxetine removal efficiency in plants with different levels of endogenous serotonin. L. minor and S. polyrhiza exhibit substantial tolerance to fluoxetine, and antioxidative enzymes are sensitive markers of this stress. Full article

Simultaneous detection of multiple neurochemicals and toxic metal ions in real time remains a major analytical challenge in neurochemistry and environmental sensing. In this study, we present a novel, biocompatible, laser-trimmed four-bore carbon fiber microelectrode (CFM) platform capable of ultra-fast, multi-analyte detection using fast-scan cyclic voltammetry (FSCV). Each of the four carbon fibers, spaced nanometers apart within a glass housing, was independently functionalized and addressed with a distinct waveform, allowing the selective and concurrent detection of four analytes without electrical crosstalk. To validate the system, we developed two electrochemical detection paradigms: (1) selective electrodeposition of gold nanoparticles (AuNPs) on one fiber for enhanced detection of cadmium (Cd²⁺), alongside dopamine (DA), arsenic (As³⁺), and copper (Cu²⁺); and (2) Nafion-modification of two diagonally opposing fibers for discriminating DA and serotonin (5-HT) from their interferents, ascorbic acid (AA) and 5-hydroxyindoleacetic acid (5-HIAA), respectively. Scanning electron microscopy and energy-dispersive X-ray spectroscopy analysis confirmed surface modifications and the spatial localization of electrodeposited materials. Electrochemical characterization in tris buffer, which mimics artificial cerebrospinal fluid, demonstrated enhanced analytical performance. Compared to single-bore CFMs, the four-bore design yielded a 28% increase in sensitivity for Cd²⁺ (147.62 to 190.02 nA µM⁻¹), 12% increase for DA (10.785 to 12.767 nA µM⁻¹), and enabled detection of As³⁺ with a sensitivity of 0.844 nA µM⁻¹, which was not possible with single-bore electrodes within the mixture of analytes. Limits of detection improved twofold for both DA (0.025 µM) and Cd²⁺ (0.005 µM), while As³⁺ was detectable down to 0.1 µM. In neurotransmitter-interference studies, sensitivity increased by 39% for DA and 33% for 5-HT with four-bore CFMs compared to single-bore CFMs, despite modest Nafion diffusion onto adjacent fibers. Overall, our four-bore CFM system enables rapid, selective, and multiplexed detection of chemically diverse analytes in a single scan, providing a highly promising platform for real-time neurochemical monitoring, environmental toxicology, and future integration with AI-based in vivo calibration models. Full article

Patients undergoing oral surgery are frequently polymedicated and preoperative prescriptions (analgesics, corticosteroids, antibiotics) can generate clinically significant drug–drug interactions (DDIs) associated with bleeding risk, serotonin toxicity, cardiovascular instability and other adverse events. This study prospectively evaluated whether large language models (LLMs) can assist in detecting clinically relevant DDIs at the point of care. Five LLMs (ChatGPT-5, DeepSeek-Chat, DeepSeek-Reasoner, Gemini-Flash, and Gemini-Pro) were compared with a panel of experienced oral surgeons in 500 standardized oral-surgery cases constructed from realistic chronic medication profiles and typical postoperative regimens. For each case, all chronic and procedure-related drugs were provided and the task was to identify DDIs and rate their severity using an ordinal Lexicomp-based scale (A–X), with D/X considered “action required”. Primary outcomes were exact agreement with surgeon consensus and ordinal concordance; secondary outcomes included sensitivity for actionable DDIs, specificity, error pattern and response latency. DeepSeek-Chat reached the highest exact agreement with surgeons (50.6%) and showed perfect specificity (100%) but low sensitivity (18%), missing 82% of actionable D/X alerts. ChatGPT-5 showed the highest sensitivity (98.0%) but lower specificity (56.7%) and generated more false-positive warnings. Median response time was 3.6 s for the fastest model versus 225 s for expert review. These findings indicate that current LLMs can deliver rapid, structured DDI screening in oral surgery but exhibit distinct safety trade-offs between missed critical interactions and alert overcalling. They should therefore be considered as decision-support tools rather than substitutes for clinical judgment and their integration should prioritize validated, supervised workflows. Full article

Background: Thunbergia alata is employed in traditional medicine to treat culture-bound syndromes such as “susto” (fright) or “espanto” (fearfulness). These conditions may correlate with depressive disorders. However, there is no evidence that this species has antidepressant properties. Aims: To characterize the antidepressant-like effect of an aqueous extract of T. alata in different paradigms and to analyze the role of brain monoamines in such actions. Methods: Independent groups of mice were treated with saline or the extract (1, 5, 10, 50, and 100 mg/kg; p.o.) and evaluated in the tail suspension (TST) and forced swimming tests (FST). Biochemical mechanisms were analyzed using inhibitors of monoamine synthesis, ligands of serotonergic receptors, and in vitro assays of MAO-A and MAO-B activity. Acute and sub-acute toxicity was evaluated. Results: The extract significantly reduced the immobility time of mice in both the TST and the FST, without affecting locomotor activity, as did the prototypical antidepressant desipramine. PCPA, AMPT, and NAN-190 abolished the extract’s effects on despair, while serotonergic ligands (8-OH-DPAT, fluoxetine, and pindolol) facilitated their antidepressant action. T. alata inhibited MAO-A and B activity. High doses of the extract produced no change in organ morphology; LD₅₀ was >2000 mg/kg. Conclusions: This is the first study to demonstrate that an aqueous extract of T. alata produces antidepressant effects mediated by the monoamine brain levels, especially serotonin. In addition to its use in culture-bounded syndromes, the present findings of safety and efficacy give support to the proposal that T. alata may be used in the treatment of depression. Full article

Background/Objectives: Neurotransmitters such as dopamine and serotonin are critical regulators of mood, cognition, and neuronal homeostasis. This study aimed to evaluate the neuropharmacological potential of Hawaiian plants by investigating their ability to modulate the expression of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), key enzymes in neurotransmitter biosynthesis. Methods: A total of 108 aqueous and methanolic extracts of Hawaiian plants were screened for cytotoxicity against PC-12 and Neuro-2A cells using the MTT assay. Fifty-six non-toxic extracts were selected and further analyzed for TH and TPH expression via quantitative real-time PCR (qPCR). Results: Several extracts significantly upregulated TH and TPH expression without inducing cytotoxicity. Extracts derived from Morinda citrifolia, Pipturus albidus, and Hedychium coronarium showed the most notable activity, suggesting their potential to enhance dopaminergic and serotonergic pathways. Conclusions: The findings highlight the promise of native Hawaiian flora as sources of neuroactive compounds that may support neuroprotection and regeneration. These results provide a foundation for in vivo studies and further exploration of novel neurotherapeutic agents. Full article

Individuals with severe mental illness face a substantially higher risk of suicide compared with the general population, with drug overdose representing one of the most common and potentially lethal methods. This narrative review explores toxidromes frequently encountered in psychiatric populations, such as opioid, anticholinergic, and serotonergic toxicity, highlighting the clinical presentation in intentional overdose. Emphasis is placed on clinical recognition, antidote-based treatment, and systems-level strategies for the prevention of lethal overdose. We conducted a comprehensive literature search of PubMed, Google Scholar, and Web of Science for English-language articles using combinations of the following keywords: mental disorders; persons with psychiatric disorders; drug overdose; poisoning; serotonin syndrome; neuroleptic malignant syndrome; anticholinergic agents/poisoning; cholinergic antagonists/poisoning; psychotropic drugs/adverse effects; substance-related disorders; drug-related side effects and adverse reactions; polypharmacy; suicide, attempted; emergency service, hospital. By embedding toxidrome awareness into routine emergency and psychiatric practice, we aim to expedite treatment and improve patient outcomes. Full article

The bidirectional relationship between epilepsy and depression illustrates shared neurobiological mechanisms of neuroinflammation, hypothalamic–pituitary–adrenal axis dysregulation, and glutamatergic dysfunction. Depression is present in 20–55% of people with epilepsy, far greater than in the general population, while depression doubles epilepsy risk 2.5-fold, indicating shared pathophysiology. Neuroinflammatory mediators (interleukin-6, tumor necrosis factor alpha, high-mobility group box 1) establish a vicious cycle: seizures exacerbate inflammation and mood disruption, and stress lowers seizure thresholds. Hippocampal damage and cortisol toxicity also link these disorders, with early life stress imprinting lifelong risk via epigenetic alteration. Genetic studies identify pleiotropic genes (brain-derived neurotrophic factor) that regulate synaptic plasticity, serotonin activity, and immune responses. New treatments target shared pathways: ketamine and AMPAkines normalize glutamate tone; mGluR5 antagonists attenuate hyperexcitability and inflammation; DNA methyltransferase inhibitors reverse aberrant DNA methylation; and probiotics manipulate the gut–brain axis by boosting neuroprotective metabolites like butyrate. Despite challenges—transient effects, precision dosing, and blood–brain barrier penetration—these advances constitute a paradigm shift toward mechanistic repair rather than symptom management. The way forward includes clustered regularly interspaced short palindromic repeats (CRISPR)-based epigenome editing, biomarker-led therapies, and combination approaches (e.g., ketamine and probiotics). Such comorbidity needs to be managed holistically through integrated neuropsychiatry care, offering hope to patients with treatment-refractory symptoms. Full article