Neurotoxicity Research最新文献

{"title":"Flavonoid Rutin Reduces Intestinal Inflammation in an Experimental Model of Parkinson's Disease.","authors":"Livia Bacelar De Jesus, Annyta Fernandes Frota, Fillipe Mendes De Araújo, Fabine Correia Passos, Nestor Adrian Guerrero Gutierrez, Luana Brunelly Araujo de Lima, Victor Diogenes Amaral Silva, Gyselle Chrystina Baccan, Marcelo Biondaro Gois, Silvia Lima Costa","doi":"10.1007/s12640-026-00789-z","DOIUrl":"10.1007/s12640-026-00789-z","url":null,"abstract":"<p><p>The enteric nervous system (ENS), a complex network of neurons and glial cells, is essential for maintaining intestinal homeostasis and is implicated in neurodegenerative diseases such as Parkinson's disease (PD). The gut-brain axis, modulated by gut microbiota (GM), is influenced by dietary compounds that can alter its composition. Despite advances in the understanding of PD pathophysiology, effective treatments remain limited, underscoring the need for novel therapeutic approaches. Among plant-derived compounds, the flavonoid rutin has shown significant antioxidant, anti-inflammatory, and neuroprotective properties in vivo. This study evaluated the effects of rutin on leukocyte infiltration, intestinal morphology, and GM composition in an experimental model of PD. Adult male Wistar rats received a stereotaxic injection of 6-hydroxydopamine (6-OHDA) and were treated orally with rutin (10 mg/kg) for 14 days. Intestinal segments were analyzed histomorphometrically, and fecal samples were assessed for the abundance of Firmicutes, Bacteroidetes, Prevotellacea, Entererobactereacea, Bifidobacterium sp and Lactobacillus sp. by PCR. Rutin administration significantly reduced intraepithelial lymphocyte infiltration and goblet cell numbers in the ileum and colon and prevented hyperplasia of Paneth cells in the ileum. Importantly, GM composition remained unchanged following rutin treatment. These findings demonstrated that rutin reduces intestinal inflammation in PD models without altering gut microbiota composition, highlighting its potential as a therapeutic strategy.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"44 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13032989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574965","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":"Decoding the RNA Shield: HNRNPC and YTHDF2 Act as Guardians of Neurons in Parkinson's Disease.","authors":"Shreya, Khadga Raj Aran","doi":"10.1007/s12640-026-00790-6","DOIUrl":"10.1007/s12640-026-00790-6","url":null,"abstract":"<p><p>Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra, resulting in hallmark motor symptoms such as tremor, bradykinesia, rigidity, and postural instability. Beyond these classical features, emerging evidence highlights the critical role of RNA modifications, particularly N6-methyladenosine (m6A), in regulating neuronal health and disease. The m6A modification is dynamically controlled by writers (METTL3, METTL14, WTAP), erasers (FTO, ALKBH5), and readers (e.g., YTHDF2, HNRNPC), which together influence RNA splicing, stability, and translation. Dysregulation of the readers HNRNPC and YTHDF2 has been implicated in oxidative stress, neuroinflammation, and dopaminergic neurodegeneration, positioning the HNRNPC/YTHDF2 axis as a central regulator of RNA metabolism and as a potential therapeutic target. In the healthy brain, HNRNPC ensures proper splicing and stabilizes transcripts essential for neuronal function, while YTHDF2 promotes the degeneration of deleterious m6A-modified RNAs to maintain neuronal homeostasis. In PD, their downregulation disrupts these processes, leading to transcript accumulation, impaired splicing, heightened neuroinflammation, oxidative stress, and apoptosis, contributing to dopaminergic neuron susceptibility and degeneration. We further highlight their role in α-synuclein regulation, dopaminergic signaling, and neuroimmune interactions, underscoring their promise as biomarkers and therapeutic targets. Finally, we discuss emerging therapeutic strategies targeting the m6A landscape, including antisense oligonucleotides (ASOs), RNA interference (RNAi), CRISPR-Cas13-based epitranscriptomic editing, and small-molecule modulators of m6A regulators. This review integrates molecular insights with therapeutic perspectives to elucidate how HNRNPC and YTHDF2 contribute to PD pathophysiology and explore novel avenues for interventions.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"44 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521564","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":"Camphor-Induced Seizures in Rats Increase the Potency of Gamma Oscillations During the Ictal Period, A Component that may Lead to Refractoriness in Seizure Control.","authors":"Priscille Fidelis Pacheco Hartcopff, Clarissa Araujo da Paz, Luciana Eiró Quirino, Thaysa de Sousa Reis, Daniella Bastos de Araujo, Rafael Dos Reis de Souza, Caio Gabriel da Silva Motta, Mateus Felipe Ferreira Araújo, Marcelo Victor Dos Santos Brito, Murilo Farias Dos Santos, Alisson Bruno Leite Lima, Axell Lins, Moisés Hamoy","doi":"10.1007/s12640-026-00793-3","DOIUrl":"10.1007/s12640-026-00793-3","url":null,"abstract":"<p><p>Particularly in the evaluation of substances that can cause neuronal hyperexcitability, triggering refractoriness to antiepileptic drugs, this has always been of interest to science. This study investigated the neurobehavioral and electrocorticographic (ECoG) characteristics of seizures induced by camphorated oil in Wistar rats and compared them to those triggered by pentylenetetrazol (PTZ), a classical chemoconvulsant model. Male rats received intraperitoneal administration of camphor (470 mg/kg), and behavioral evolution was monitored to characterize seizure onset and progression. ECoG recordings from the motor cortex were acquired for 30 min to assess cortical oscillatory activity during ictal and interictal periods. Camphor administration elicited six distinct and rapidly evolving behavioral patterns culminating in generalized clonic seizures with loss of postural reflexes. ECoG analyses revealed cyclic high-power ictal discharges interspersed with low-power interictal activity, resembling PTZ-induced seizures but with lower potency. Evaluation of anticonvulsant efficacy demonstrated that camphor-induced seizures were refractory to phenobarbital and phenytoin, whereas diazepam and propofol significantly reduced β- and γ-band power and effectively controlled convulsive activity. These findings suggest that camphor produces a reproducible chemoconvulsant model characterized by prominent cortical excitability and partial pharmacoresistance, supporting its potential utility in neurotoxicological and neuropharmacological studies aimed at understanding seizure mechanisms and testing antiepileptic drug responsiveness.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"44 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13013342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513800","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":"Decreased Length of Locus Coeruleus Norepinephrine Axons and Increased Amyloid Beta Pathology in Male APP/PS1 Mice During Protracted Abstinence From Alcohol.","authors":"Ivy J Z Garland, Shaydel Engel, Matthew Scalf, Nichole R Payne, Anna M Lee, Steven M Graves","doi":"10.1007/s12640-026-00794-2","DOIUrl":"10.1007/s12640-026-00794-2","url":null,"abstract":"<p><p>Alzheimer’s disease (AD) is the leading cause of dementia and evidence suggests that alcohol, the most commonly used addictive substance, may increase AD risk. Locus coeruleus (LC) neurons are the primary source of norepinephrine in the brain and these neurons degenerate early in AD. In rodent models, lesioning the LC increases amyloid beta (Aβ) pathology suggesting that LC integrity and norepinephrine signaling obstruct Aβ pathogenesis. We recently reported a decrease in the number of LC norepinephrine neurons and increased Aβ pathology when measured after protracted abstinence from chronic intermittent alcohol consumption in female APP/PS1 mice. Clinically, female subjects are at a higher risk for AD; additionally, female mice consume more alcohol than male mice making it unclear as to whether alcohol consumption would produce similar adverse outcomes in male subjects. To address this gap, male APP/PS1 and non-transgenic mice underwent chronic intermittent access (IA) to alcohol followed by protracted abstinence with water drinking controls run in parallel, consistent with our prior study. In contrast to our previous results with female mice, the number of LC norepinephrine neurons was unchanged in male APP/PS1 mice that had IA to alcohol; however, the length of LC axons was decreased and Aβ pathology was increased in male APP/PS1 mice that consumed alcohol. These data demonstrate that alcohol consumption during early adulthood results in negative consequences in male APP/PS1 mice, although the effect may not be as severe as previously observed in female mice.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"44 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504419","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":"Role of LncRNA NEAT1 in Alzheimer's Disease: Pathophysiological Insights and Therapeutic Approaches.","authors":"Shreya, Gursimran Singh, Garry Hunjan, Khadga Raj Aran","doi":"10.1007/s12640-026-00792-4","DOIUrl":"10.1007/s12640-026-00792-4","url":null,"abstract":"<p><p>AD is a progressive neurodegenerative disease characterized by oxidative stress (OS), mitochondrial dysfunction, and synaptic dysfunction. Long non-coding RNAs (lncRNAs) play a crucial role in gene expression at transcriptional and post-transcriptional levels. Among them, NEAT1 is a structural component of nuclear paraspeckles that maintains transcriptional stability and coordinates stress responses. NEAT1 serves as a molecular scaffold that interacts with RNA-binding proteins to regulate pre-mRNA splicing, transcriptional repression, and cellular homeostasis. NEAT1 expression is elevated in AD and is associated with neuroinflammation, synaptic plasticity alterations, and neuronal apoptosis. It epigenetically regulates targets including CAV2, TGFB2, TGFBR1, and FZD3, suggesting context-dependent protective and pathogenic roles in AD progression. This multifaceted nature highlights NEAT1 as a potential noninvasive biomarker and therapeutic target. This review summarizes the structure and function of NEAT1, its regulatory role in the pathophysiology of AD, and new therapeutic approaches to regulate its expression.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"44 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494336","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":"Tubuloside B Alleviates Aβ_25-35 Induced PC12 Cell Injury by Attenuating Pyroptosis, Apoptosis and Excessive Autophagy.","authors":"Hao Yang, Rao Fu, Yueyang Duan, Yongjiao Hua, Tianyu Wei, Guiping Li, Xinru Gu, Ming Li, Xiao Yu, Liang Li, Liang Cao, Zhen-Zhong Wang, Chenfeng Zhang, Yaozhong Lv, Mingli He, Wei Xiao","doi":"10.1007/s12640-026-00791-5","DOIUrl":"10.1007/s12640-026-00791-5","url":null,"abstract":"<p><p>Cistanche, a traditional Chinese medicine with reported neuroprotective effects, contains multiple bioactive constituents whose specific mechanisms of action remain incompletely defined. Here, we aimed to identify a key neuroprotective component and explore its potential mechanism against Aβ-induced neurotoxicity. Fourteen commercially available Cistanche-derived compounds were screened for neuroprotection in an Aβ25-35 (Aβ fragment 25–35)-injured PC12 cell model. The most active compound, Tubuloside B (TB), was further investigated using polymerase chain reaction (PCR) array, immunoblotting, flow cytometry, immunofluorescence, and mitochondrial function assays. TB exerted concentration-dependent protective effects in the Aβ25-35-injured PC12 model. Aβ25-35 exposure was associated with marked activation of pyroptotic signaling, characterized by caspase-1 activation, GSDMD cleavage, and increased interleukin (IL)-1β/IL-18 levels. These alterations were substantially blunted in the presence of TB. Modulation of the absent in melanoma 2 (AIM2) inflammasome pathway was further supported by reduced AIM2 expression and diminished apoptosis-associated speck-like protein containing a CARD (ASC) speck formation. Mitochondrial perturbations induced by Aβ25-35, including excessive mitochondrial reactive oxygen species (ROS) generation, membrane depolarization, and cytosolic mtDNA accumulation, were concurrently ameliorated by TB. In addition, markers of apoptosis and dysregulated autophagy were partially normalized following TB treatment. These findings suggest that TB may contribute to neuroprotection in an Aβ25-35-induced PC12 cell model, potentially involving modulation of mitochondrial dysfunction–associated inflammasome activation and downstream cell death pathways. Given the in vitro design and limited sample size, these results should be considered preliminary and warrant further validation in vivo.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"44 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486684","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":"Modulation of NMDA Receptor and TRPM4 Activity in Hippocampal Neurons with the NMDA Receptor/TRPM4 Interface Inhibitor Brophenexin.","authors":"Jordan Casby, Rachel K Allen, Ezequiel Marron Fernandez de Velasco, Stanley A Thayer","doi":"10.1007/s12640-026-00788-0","DOIUrl":"10.1007/s12640-026-00788-0","url":null,"abstract":"<p><p>Excitotoxic signaling mediated by N-methyl-D-aspartate receptors (NMDARs) is inhibited by NMDAR/TRPM4 complex inhibitors such as brophenexin (BPN). We used rat hippocampal neurons grown in culture to determine the effects of BPN on NMDAR and TRPM4 function. NMDA evoked concentration-dependent increases in intracellular Ca2+ that were inhibited by 10 µM BPN in a non-competitive manner. In contrast, the TRPM4 inhibitor 4-chloro-2-(2-(naphthalene-1-yloxy) acetamido) benzoic acid (NBA) increased the potency of NMDA at 22 °C. BPN inhibition of NMDAR-mediated increases in Ca2+ was fully reversible and recovered by rapid (30 s) and slow (90 min) processes. The rapid phase of recovery from BPN inhibition was mediated by trafficking through recycling endosomes as indicated by blockade of this phase with bafilomycin A1 an agent that prevents endosomal acidification. The full recovery of NMDAR function observed 90 min after washout of BPN was not affected by this treatment. Immunocytochemistry experiments suggested that BPN did not directly alter NMDAR trafficking but instead changes in surface and internal GluN2B immunoreactivity were likely homeostatic responses to inhibition of NMDAR function by BPN. In the presence of MK-801 to block NMDARs, 10 µM NBA inhibited spontaneous network-driven Ca2+ spiking by 74 ± 11% whereas 10 µM BPN reduced activity by 49 ± 6%. Thus, BPN inhibits TRPM4-dependent activity. In summary, BPN is a non-competitive, fully reversible inhibitor of NMDAR-mediated Ca2+ influx and produces a modest inhibition of TRPM4 function. Functional inhibition of these ion channels likely contributes to the neuroprotective properties of NMDAR/TRPM4 interface inhibitors.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"44 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12965916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366167","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":"Investigating brain-derived neurotrophic factor (BDNF) changes in three main rodent models of autism spectrum disorder (ASD): a systematic review.","authors":"Marzieh Jalalian-Javadpour, Mahdi Khaledian, Hamed Moradi, Hamidreza Behnoud, Mandana Sajjadi, Batool Ghorbani Yekta, Salar Vaseghi","doi":"10.1007/s12640-026-00787-1","DOIUrl":"10.1007/s12640-026-00787-1","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social impairments, and repetitive and aggressive behaviors. The pathophysiology of ASD still remains unclear, while the population with ASD is 1/36 in children in the USA in 2024. Evidence suggests a wide range of inconsistent changes in brain-derived neurotrophic factor (BDNF), the most important neurotrophin in the central nervous system, in ASD. The present systematic review investigated studies that examined BDNF levels in three main ASD-like models in rodents [induced by valproic acid (VPA) and propionic acid (PPA), and in the BTBR mouse strain] in accord with PRISMA guidelines and in PubMed database. Forty-two studies were included. Most studies used male rats/mice. The results showed ASD model induced by VPA often leads to decreased BDNF, although unchanged or increased BDNF levels were also reported. ASD model induced by PPA leads to both increased and decreased BDNF. BDNF changes in BTBR mouse strain were also inconsistent. We found that the type of molecular assay appears to be important in evaluating BDNF. Also, few evidence showed a role for postnatal day and sex difference in BDNF changes in ASD-like rodent models. In addition, some studies have shown the potential role of the brain region in BDNF changes in different ASD-like models. In conclusion, it was suggested that inconsistencies in BDNF changes in rodent models of ASD may be related to the type of the molecular assay, the brain region, ASD model, sex, or even the postnatal day. However, evidence is still insufficient.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"44 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290591","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":"Niacin Protects iPSC-Derived Neurons from Chemotherapy-Induced Toxicity.","authors":"Nidaa A Ababneh, Mohammad H Gharandouq, Mohammad A Ismail, Razan AlDiqs, Omar Hamdan, Qais Musa, Raghda Barham, Momen Sarhan, Sofian Al Shboul, Amira T Masri, Areej Abuhammad, Abdalla Awidi, Tareq Saleh","doi":"10.1007/s12640-026-00784-4","DOIUrl":"10.1007/s12640-026-00784-4","url":null,"abstract":"<p><p>Neurotoxicity remains a major dose-limiting adverse effect of cancer therapy. Previous studies have indicated that niacin can promote neuroprotective effects primarily through antioxidative mechanisms. In this study, we investigated the neuroprotective role of niacin on human induced pluripotent stem cell-derived motor neurons (iPSC-MNs) subjected to three neurotoxic chemotherapeutic agents: cisplatin, methotrexate, and 5-fluorouracil. Our findings revealed that niacin significantly enhanced neuronal viability, as evidenced by MTT and LDH assays, with the most pronounced protection observed in 5-fluorouracil–treated iPSC-MNs. Moreover, niacin markedly reduced reactive oxygen species (ROS) generation across all chemotherapy treatment conditions. Additionally, niacin mitigated mitochondrial membrane potential (MMP) decrease and promoted ATP production, indicating its ability to counteract chemotherapy-induced mitochondrial dysfunction. Collectively, our results highlight the potential of niacin as a form of supportive therapy for the protection of neurons against CIN and demonstrate the utility of iPSC-derived neurons as a relevant model for investigating various forms of CIN including chemotherapy-induced peripheral neuropathy (CIPN) or cognitive impairment (CICI).</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"44 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271548","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":"Long-Term Effects of Arsenic Poisoning during Infancy Due to Contaminated Milk Powder: A Systematic Review.","authors":"Khaled Saad, Ramez M Odat, Ahmed Mansour, Ahmed Elbataa, Abdulhalim A Kikhia, Saddik Haddad, Mohamed Z Kouta, Mohamed G Nada, Lama Alessawy, Romany Rezk Melad, Ibrahim Hassan, Anas H Heiba, Shimaa Elwardany Aly, Zakaria M Abdel-Sadek, Wesam M Hussein, Ibraheem Altamimi, Mohamad-Hani Temsah, Anas Elgenidi","doi":"10.1007/s12640-026-00783-5","DOIUrl":"10.1007/s12640-026-00783-5","url":null,"abstract":"<p><p>Arsenic is a prevalent and significant cause of poisoning worldwide, leading to both acute and chronic toxicity. The life-threatening nature of arsenic toxicity is evident in its link to fatal health conditions in different parts and systems of the body. We aimed to conduct a systematic review of the existing literature on long-term health outcomes following arsenic poisoning during infancy. Following the PRISMA 2020 guidelines, we systematically searched the PubMed, Embase, Scopus, Cochrane, and Web of Science databases from their inception up to May 2025. The final selection included seven studies that met the inclusion criteria, with a total of 15,701 participants. A risk assessment of arsenic exposure through powdered milk was done, and a quality assessment was performed. Seven studies were included. Arsenic poisoning due to contaminated milk powder has many effects on multiple organs. This review synthesizes evidence demonstrating that arsenic poisoning during infancy is associated with increased all-cause mortality, primarily attributable to malignancies, neurological disorders, and persistent alterations in somatic development. Exposed individuals exhibited reduced adult height, elevated serum alkaline phosphatase concentrations, and an increased incidence of malignancy. Dental sequelae comprised enamel hypoplasia and gingivitis; dermatological manifestations included persistent punctate hypomelanosis and other cutaneous abnormalities enduring decades. This systematic review delineates the multifaceted long-term health consequences of infantile arsenic poisoning from contaminated milk powder, encompassing malignancies, genitourinary, respiratory, cardiovascular, and neurological diseases. These findings establish arsenic exposure during critical developmental windows as a lifelong health determinant that requires specialized, multidisciplinary medical surveillance protocols. Regulatory standards for arsenic in infant nutrition products need to be reevaluated to prevent similar tragedies from occurring.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"44 1","pages":"8"},"PeriodicalIF":3.9,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157558","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}