Neurotoxicology and teratology最新文献

{"title":"A comprehensive review of the neurobehavioral and neurotoxic effects of 6PPD-Q in fish, rodents, and humans.","authors":"Emma Ivantsova, Austin Lu, Christopher J Martyniuk","doi":"10.1016/j.ntt.2026.107725","DOIUrl":"10.1016/j.ntt.2026.107725","url":null,"abstract":"<p><p>N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is a widely used tire additive that undergoes environmental transformation to 6PPD-quinone (6PPD-Q), which is ubiquitously detected in environmental matrices. Increasing evidence demonstrates that exposure to 6PPD-Q adversely affects organisms through neurobehavioral disruption and neurotoxicity. While studies document behavioral abnormalities and molecular alterations, a comprehensive synthesis linking these outcomes remains limited. The objective of this review was to synthesize current literature reporting neurobehavioral and neurotoxic effects of 6PPD-Q in fish, rodents, and humans using experimental and computational approaches. Using PRISMA guidelines, a search was conducted in PubMed and Google Scholar using several key phrases related to 6PPD-Q and neurotoxicity, capturing 1874 records. Relevant articles were assessed by full-text review for criteria eligibility, and the final review included 27 articles. In fish, exposure to 6PPD-Q can alter neurobehaviors like locomotor activity, anxiety-like responses, social and aggressive behaviors, and disturbances in circadian-regulated activities. Such behavioral outcomes correspond closely with neurotransmitter imbalance, neuroendocrine disruption, blood-brain barrier dysfunction, and transcriptome changes affecting neural signaling pathways. In rodents, repeated or chronic exposure to 6PPD-Q leads to neuronal damage, cognitive impairment, anxiety-like behavior, and memory deficits. Human biomonitoring and mechanistic studies further associate 6PPD-Q exposure with oxidative stress, mitochondrial dysfunction, and molecular responses relevant to neurological diseases. Leveraging the Comparative Toxicogenomics Database, computational analysis revealed entities associated with 6PPD-Q in the database were related to Alzheimer's disease, dopaminergic synapses, neurotrophin signaling pathways, and Parkinson's disease. Taken together, data suggests that 6PPD-Q may interfere with neuronal signaling, connectivity, and plasticity, leading to behavioral deficits. Based on predictive docking scores using fish, rodent, and human orthologs, 6PPD-Q may interact with tyrosine hydroxylase and L-dopa decarboxylase which can potentially lead to disrupted dopamine biosynthesis pathways. Given the widespread environmental presence of 6PPD-Q and its continuous introduction into aquatic ecosystems, characterizing such mechanisms is critical for improving ecological and human health risk assessments.</p>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":" ","pages":"107725"},"PeriodicalIF":3.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 37th ENTIS (European network of teratology information services) conference abstracts September 3rd – 5th, 2026, Leiden, The Netherlands","authors":"","doi":"10.1016/j.ntt.2026.107616","DOIUrl":"10.1016/j.ntt.2026.107616","url":null,"abstract":"","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"116 ","pages":"Article 107616"},"PeriodicalIF":3.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148693863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of subchronic late-gestational nicotine exposure on postpartum maternal behavior in Wistar rats: An exploratory pilot study","authors":"Wilmer Yamid González-Cabra,&nbsp;María del Pilar Santacruz Ortega,&nbsp;Andrés Carrillo-González","doi":"10.1016/j.ntt.2026.107615","DOIUrl":"10.1016/j.ntt.2026.107615","url":null,"abstract":"<div><h3>Objective</h3><div>This exploratory pilot study evaluated whether subchronic late-gestational oral nicotine exposure alters postpartum maternal behavior in Wistar rats.</div></div><div><h3>Methods</h3><div>Twelve pregnant Wistar rats were obtained in three successive intake batches and randomly assigned to experimental or control groups. Control animals received a 2% saccharin solution; experimental animals received nicotine (nominal 200 μg/mL) in 2% saccharin solution ad libitum from gestational day 7 through parturition. The initial concentration of 200 μg/mL produced two maternal deaths and one embryonic reabsorption in the first experimental batch; the solution was diluted approximately 1:3 to ∼50 μg/mL for the third experimental batch. Postpartum maternal behavior was scored from 15-min light-phase video samples (three 5-min blocks at 5-s instantaneous sampling) on each of the 14 postpartum days. Dependent variables were daily frequency counts of 19 ethogram behaviors organized into proximal, nest-related, motor, and self-maintenance categories. Primary analyses were 2 × 14 mixed repeated-measures ANOVAs. Fluid consumption, litter parameters, and cohort attrition are also reported.</div></div><div><h3>Results</h3><div>Experimental dams reduced solution consumption by approximately 81% relative to their pre-nicotine water baseline, indicating that actual nicotine exposure was substantially below the nominal concentration. Among the three surviving dams per group, proximal maternal behaviors showed no reliable group differences on either parametric or non-parametric tests. The clearest between-group difference was in eating frequency (controls &gt; experimentals; F(1, 4) = 48.96, <em>p</em> = .002, ηp² = 0.92). A significant Day × Group interaction was observed for locomotion, concentrated on postpartum days 11–12.</div></div><div><h3>Conclusions</h3><div>In this small pilot, subchronic late-gestational nicotine exposure did not produce consistent alterations in core proximal maternal behaviors among surviving dams, but was associated with substantial gestational losses, reduced maternal fluid intake, a qualitative low-pup-birth-weight observation, and a postpartum eating-frequency difference that cannot be unambiguously attributed to nicotine pharmacology. The findings are hypothesis-generating and motivate adequately powered replication with cotinine verification and gravimetric pup-weight measurement.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"116 ","pages":"Article 107615"},"PeriodicalIF":3.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periconceptional and prenatal tobacco exposure and early externalizing behavior: Developmental pathways through maternal distress and language delay","authors":"Madeleine Singer,&nbsp;Julie A. Kable,&nbsp;Claire D. Coles","doi":"10.1016/j.ntt.2026.107614","DOIUrl":"10.1016/j.ntt.2026.107614","url":null,"abstract":"<div><div>Periconceptional and prenatal tobacco exposure (PPTE) has been associated with early externalizing behaviors, yet the developmental pathways underlying this association remain poorly understood. The purpose of this study was to examine potential mechanisms through which PPTE may relate to child behavior. Data were drawn from a prospective, longitudinal cohort of mother-child dyads recruited at birth. The final sample included 203 mothers, predominantly White, with lower income, education, and partnership rates observed among heavier smoking groups. The study collected socio-demographic information and measures of maternal psychological distress, child language ability and behavior. PPTE, defined in this study as a continuous variable representing the average number of cigarettes smoked per day three months prior and during pregnancy, was the primary exposure variable. Maternal psychological distress and child language development were evaluated as potential intervening pathways. A path model was used to evaluate the relative contribution of direct and indirect effects of PPTE on externalizing behavior at 24-months. PPTE significantly predicted both greater maternal psychological distress and poorer child language ability. Both variables were associated with higher externalizing behaviors. In the indirect effects model, the direct effect of PPTE on externalizing behaviors was nonsignificant, while multiple indirect pathways were significant, including via child language development and maternal psychological distress. Findings suggest that the association between PPTE and externalizing behaviors may operate indirectly through maternal psychological distress and child language development.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"116 ","pages":"Article 107614"},"PeriodicalIF":3.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal methamphetamine exposure increased addiction vulnerability through neural circuit dysfunction and epigenetic modifications in offspring","authors":"Yuqi Wang ,&nbsp;Daiju Tao ,&nbsp;Rongji Sun ,&nbsp;Li Zhang ,&nbsp;Renhua Yang ,&nbsp;Ying Shen ,&nbsp;Haiyu Su ,&nbsp;Bingquan Chen ,&nbsp;Zhiqiang Shen ,&nbsp;Peng Chen ,&nbsp;Bo He","doi":"10.1016/j.ntt.2026.107604","DOIUrl":"10.1016/j.ntt.2026.107604","url":null,"abstract":"<div><div>Methamphetamine (METH), a type of synthetic drug with effects similar to amphetamines, remains a significant public health concern, particularly among women of childbearing age. Prenatal methamphetamine exposure (PME) has been demonstrated to negatively affect fetal neurodevelopment and increase addiction in exposed individuals. Although there is increasing evidence of transgenerational effects, the molecular mechanisms that mediate addiction vulnerability induced by PME are not yet fully understood. In this comprehensive review, we combine findings from epidemiology and mechanistic studies using animal models to create a more complete picture regarding the mechanisms by which PME changes the neural circuitry, through its effects on the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus. There is an increasing body of research on epigenetics that illustrates a relationship between epigenetic alterations to DNA via methylation, histone modifications, and the dysregulation of non-coding RNAs in neurodevelopmental programming and the eventual treatment outcomes for substance use disorders. Elucidating these neurobiological mechanisms provides critical insights for identifying vulnerable populations, developing targeted interventions, and establishing evidence-based strategies to mitigate addiction risk in PME-affected offspring.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"115 ","pages":"Article 107604"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postnatal environment differentially modulates neurodevelopmental outcomes following voluntary prenatal oxycodone exposure in rats","authors":"Kelsea R. Gildawie ,&nbsp;Kerri E. Budge ,&nbsp;Sara B. Isgate ,&nbsp;Jillian Celatka ,&nbsp;Megan Gulsby ,&nbsp;Cora C. Cunningham ,&nbsp;Fair M. Vassoler ,&nbsp;Elizabeth M. Byrnes","doi":"10.1016/j.ntt.2026.107603","DOIUrl":"10.1016/j.ntt.2026.107603","url":null,"abstract":"<div><div>As prenatal opioid exposure becomes increasingly prevalent, understanding which neurodevelopmental effects are amenable to postnatal intervention has become a critical question. Clinically, prenatal exposure and maternal factors that affect offspring development often co-occur, making it difficult to determine which developmental outcomes are directly attributable to drug effects versus postnatal environmental influences. Preclinical models can be useful in disentangling these interacting factors. Using a rat model of voluntary maternal Oxycodone (Oxy) self-administration, we examined whether postnatal rearing environment could ameliorate neonatal opioid withdrawal syndrome (NOWS)-like symptoms. Cross-fostering separated prenatal drug effects from postnatal rearing and revealed differential sensitivity to environmental modification. Altered ultrasonic vocalizations were rescued when Oxy-exposed offspring were reared by drug-naïve dams, while increased motor activity persisted regardless of rearing condition. Oxy-exposed offspring reared by Oxy-exposed dams showed a distinct developmental trajectory characterized by increased vocal power and reduced frequency variability. These early alterations persisted across the postnatal period. Unexpectedly, maternal opioid intake levels during pregnancy did not predict NOWS-like symptom severity. However, early vocalization patterns did show group-specific predictive relationships with adult markers (plasma corticosterone and nucleus accumbens MeCP2 expression), suggesting potential continuity between early behavioral alterations and later physiological changes. The functional significance of these relationships requires further investigation. Overall, some, but not all, developmental effects of prenatal opioid exposure could be ameliorated by the postnatal rearing environment. These findings suggest that early behavioral profiles may help identify offspring at greatest risk for persistent developmental alterations, highlighting the potential value of early assessment and postnatal intervention.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"115 ","pages":"Article 107603"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spermatogenic timing, dose, and route of administration as determinants of paternal transmission of developmental neurotoxicity","authors":"Issam Rimawi,&nbsp;Joseph Yanai","doi":"10.1016/j.ntt.2026.107605","DOIUrl":"10.1016/j.ntt.2026.107605","url":null,"abstract":"<div><div>Growing evidence challenges the long-standing assumption that the paternal germline is insulated from environmental perturbation and identifies preconception paternal exposure as an underrecognized pathway of developmental neurotoxicity. Across mammalian models, paternal exposure to substances of abuse, including cocaine, nicotine, ethanol, morphine, and cannabinoids, induces reproducible, often sex-specific alterations in offspring brain function and behavior, including changes in cognition, stress responsivity, reward processing, and affective behaviors, accompanied by transcriptional and epigenetic modifications. A critical but underappreciated determinant of these outcomes is exposure design, particularly exposure duration relative to the spermatogenic cycle, which emerges as a primary toxicodynamic relevant variable. Exposures spanning a full spermatogenic cycle frequently produce persistent neurobehavioral and molecular alterations, whereas shorter exposures targeting late spermatids or mature sperm can also generate robust offspring phenotypes, highlighting stage-specific germ cell vulnerability. Importantly, delaying mating beyond a complete spermatogenic cycle often attenuates offspring effects, suggesting that temporal separation between exposure and conception may mitigate neurodevelopmental risk. Mechanistically, paternal exposures disrupt sperm epigenetic regulation, including altered DNA methylation, histone modifications, and small RNA profiles, often linked to germline oxidative stress as a potential upstream mediator. Exposure dose and route further modulate transmission through pharmacokinetic effects on systemic and germline exposure. We propose a stage-specific framework in which paternal transmission magnitude and persistence are primarily determined by exposure duration relative to spermatogenesis, with dose and route acting as key modifiers. This framework integrates behavioral and molecular findings and provides a biologically grounded basis for developmental neurotoxicity risk assessment and male preconception health.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"115 ","pages":"Article 107605"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bromelain mitigates monosodium glutamate-induced neurobehavioral impairment in mice by modulating AChE-MAO-GAD and oxido-inflammatory pathways: Experimental and computational insights","authors":"Joseph Chimezie ,&nbsp;Noah A. Omeiza ,&nbsp;Oludare M. Ogunyemi ,&nbsp;Abayomi M. Ajayi ,&nbsp;Jude I. Abeje ,&nbsp;Nafisat O. Abdullahi ,&nbsp;Grace O. Isehunwa ,&nbsp;Solomon Owumi ,&nbsp;Temitope G. Adedeji","doi":"10.1016/j.ntt.2026.107586","DOIUrl":"10.1016/j.ntt.2026.107586","url":null,"abstract":"<div><div>Excessive exposure to monosodium glutamate (MSG) induces glutamate-mediated excitotoxicity, oxidative stress, and neuroinflammation, culminating in neurobehavioral impairments. Bromelain, a cysteine protease derived from <em>Ananas comosus</em>, exhibits potent antioxidative and anti-inflammatory properties; however, its potential to attenuate excitotoxic neuronal injury remains insufficiently characterized. This study investigated the neuroprotective effects of bromelain against MSG-induced neurotoxicity through integrated behavioral, biochemical, histological, and computational analyses. Male Swiss mice (7–8 weeks) received MSG (4 g/kg, i.p.) to induce excitotoxicity and were subsequently treated orally with bromelain (50 or 100 mg/kg) or fluoxetine (1 mg/kg) for 21 days. Behavioral tests assessed locomotor, cognitive, and affective functions, while biochemical and histological analyses evaluated oxidative stress, neuroinflammatory markers, and neurotransmitter-modulating enzyme activities. In silico AlphaFold3 modeling and protein–protein docking were employed to elucidate bromelain's interactions with acetylcholinesterase (AChE), monoamine oxidase-B (MAO-B), and glutamate decarboxylase (GAD). Bromelain treatment significantly ameliorated MSG-induced behavioral deficits, restored cortical and hippocampal redox balance, suppressed pro-inflammatory cytokines, and preserved neuronal cytoarchitecture. It normalized neurotransmitter metabolism by inhibiting AChE and MAO-B activities while enhancing GAD function. AlphaFold3 modeling revealed a compact, high-confidence bromelain conformation (pLDDT &gt;90) with strong predicted binding affinities to catalytically active residues of AChE, MAO-B, and GAD, supporting its multi-target neuromodulatory role. Altogether, these findings provide the first integrated experimental and computational evidence that bromelain confers neuroprotection by regulating redox homeostasis, inflammation, and neurotransmitter signaling, highlighting its promise as a nutraceutical candidate for mitigating glutamate-mediated neurodegenerative disorders.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"114 ","pages":"Article 107586"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiles of polysubstance exposure in youth with fetal alcohol spectrum disorders and the association with neurodevelopmental outcomes","authors":"Madeline N. Delage ,&nbsp;Emily L. Speybroeck ,&nbsp;Alesia A. Richardson ,&nbsp;Lynn L. Cole ,&nbsp;Carson Kautz-Turnbull ,&nbsp;Christie L.M. Petrenko","doi":"10.1016/j.ntt.2026.107585","DOIUrl":"10.1016/j.ntt.2026.107585","url":null,"abstract":"<div><h3>Background</h3><div>Prenatal polysubstance exposure is highly prevalent among individuals with fetal alcohol spectrum disorders (FASD), yet little research has examined how specific patterns of co-exposure relate to neuropsychological outcomes. While alcohol is a known teratogen, other substances such as opioids, stimulants, cannabis, and nicotine also disrupt neurodevelopmental processes. Prior studies often assess single substances in isolation, failing to reflect real-world exposure patterns. Identifying meaningful patterns of co-occurring exposures and their associations with neuropsychological outcomes is critical for advancing targeted assessment and intervention.</div></div><div><h3>Methods</h3><div>Latent class analysis was conducted on data from 635 youth with FASD (mean age of diagnosis 7.4 years, range 0.24–21.61) to identify distinct profiles of prenatal exposure to six substances: alcohol, nicotine, marijuana, opioids, cocaine, and other drugs. Class differences in neuropsychological functioning, postnatal experiences, and demographics were examined using the Bolck, Croon, and Hagenaars method.</div></div><div><h3>Results</h3><div>A three-class solution demonstrated best model fit (AIC = 3945.216, saBIC = 3970.790, aLRT = 18.521, <em>p</em> = .006). Classes comprised of an all-exposure (Class 1, 47%), mainly alcohol exposed (Class 2, 46%), and mainly opioid exposed (Class 3, 7%). Significant between-class differences emerged across domains of memory, motor speed, sensory processing, and child-reported anxiety (χ² = 9.264–42.659, <em>p</em> = .046–0.001). Class 2 demonstrated significantly greater neuropsychological challenges, while Class 3 demonstrated high sensory sensitivity and anxiety. Results also reveal caregiver disruption was more prevalent in Class 2.</div></div><div><h3>Discussion</h3><div>Findings highlight heterogeneity in neuropsychological outcomes based on distinct patterns of prenatal polysubstance exposures. Neuropsychological assessment remains essential for capturing this variability and informing individualized, exposure-responsive care.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"114 ","pages":"Article 107585"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S-adenosyl-L-methionine reverses ethanol-induced developmental toxicity in FASD model of Danio rerio embryos via dual-modulation of oxidative stress and glutathione homeostasis","authors":"Prasanth Babu Nandagopal,&nbsp;Anu Varghese Kaithamattathil,&nbsp;Gopika Jayakrishnan,&nbsp;Sampath Raghul Kannan,&nbsp;Ramasamy Tamizhselvi,&nbsp;Venkatraman Manickam","doi":"10.1016/j.ntt.2026.107589","DOIUrl":"10.1016/j.ntt.2026.107589","url":null,"abstract":"<div><div>Fetal Alcohol Spectrum Disorder (FASD) represents a major global public health concern, affecting approximately 7.7 per 1000 births worldwide and remains as the most common preventable cause of lifelong neurodevelopmental impairment. Despite its prevalence, current clinical interventions are largely symptom-supportive and fail to address the underlying developmental pathology, underscoring the need for targeted, mechanism-based therapeutic strategies. Given the central involvement of oxidative stress and inflammation in FASD pathogenesis, this study evaluated the protective efficacy of S-adenosyl-L-methionine (SAMe), a key metabolic intermediate and universal methyl donor, using a zebrafish embryo model because of its high translational relevance and optical transparency. Fertilized embryos were exposed to 1.25% ethanol and co-treated with SAMe (15 and 30 μM) until 96 h post-fertilization (hpf). Ethanol exposure resulted in reduced survival and hatching rates, cardiac rhythm abnormalities, pronounced morphological defects, and compromised tissue integrity. SAMe treatment, particularly at 30 μM, significantly ameliorated these developmental abnormalities and associated biochemical dysregulations. Mechanistically, SAMe exerted a dual protective effect by restoring glutathione biosynthesis and attenuating oxidative stress-driven inflammatory responses. This was evidenced by marked reductions in reactive oxygen species, apoptosis, lipid peroxidation, and nitric oxide levels, alongside significant downregulation of pro-inflammatory cytokines, including <em>TNF-α</em> and <em>IL-1β</em>. Importantly, these biochemical and molecular improvements were consistently translated into phenotypic rescue, with substantial normalization of tissue architecture and developmental morphology. Collectively, these findings establish SAMe as a promising anti-teratogenic intervention that directly targets core oxidative and inflammatory pathways underlying FASD, highlighting its potential translational relevance as a mechanism-driven therapeutic strategy.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"114 ","pages":"Article 107589"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}