Evidence cluster — Pet rat and mouse (Rattus norvegicus) toxicology (peer-reviewed, Europe PMC)

Evidence: Pet rat and mouse (Rattus norvegicus) toxicology

Source: Europe PMC (Europe PubMed Central) REST search — first-hand peer-reviewed abstract records, pulled 2026-08-01. Queries covered toxicology, poisoning, intoxication, heavy metals, mycotoxins and (for relevant taxa) envenomation for Rattus norvegicus. The cluster returns 12 representative studies with abstracts below. Abstract text is verbatim from source; each study is traceable by PMID.

Studies

• PMID 42483836 (2026, Analytical chemistry) — A Multi-Analyte-Responsive, Multi-Organ-Imaging, Dual-NIR-Emissive Fluorescent Probe for Visualizing Pyroptosis-Mediated Hg&lt;sup&gt;2+&lt;/sup&gt;-Induced Hepatorenal Dysfunction.. Abstract (opening): Mercury ions (Hg²⁺) are highly toxic heavy metals that are widely distributed in the environment and pose a serious threat to both ecosystems and human health. After entering the body, mercury preferentially accumulates in the liver and kidneys, underscoring the importance of early detection of acute and chronic hepatorenal injuries. Although fluorescent probes have been widely explored for disease diagnosis, most existing systems cannot achieve simultaneous in vivo imaging of the liver and kidneys, nor can they monitor multiple pathological parameters during hepatorenal injury, thus limiting their utility in evaluating Hg²⁺-induced multiorgan damage. In this study, we developed a multifunctional fluorescent probe, <b>VPO</b>, with high sensitivity and good biocompatibility, which can be used to monitor polarity, viscosity, and ONOO^- levels in cells. Using <b>VPO</b>, we observed, for the first time, a significant increase in ONOO^- during pyroptosis, accompanied by an elevated mitochondrial viscosity and reduced polarity. In addition, <b>VPO</b> successfully enabled the real-time visual monitoring of these changes in mercury-exposed cells, zebrafish, and mice. Moreover, its multiresponsive property enabled the evaluation of the therapeutic efficacy of <i>N</i>-acetylcysteine (NAC) against Hg²⁺-induced hepatorenal injury. NAC alleviated hepatic and renal mitochondrial oxidative stress, as well as pyroptosis-related inflammatory signaling, by reversing Hg²⁺-induced biomarker abnormalities. In summary, these findings demonstrate that <b>VPO</b> provides a comprehensive platform for the early diagnosis, therapeutic evaluation, and mechanistic investigation of mercury poisoning.

Source: https://pubmed.ncbi.nlm.nih.gov/42483836/

• PMID 42364866 (2026, Environmental pollution (Barking, Essex : 1987)) — Co-exposure to environmental lead and hypertension exacerbates anxiety and depression via mtDNA-mediated cGAS phase separation.. Abstract (opening): Environmental exposure to heavy metals such as lead (Pb) and the growing prevalence of hypertension (HTN) represent significant and often coexisting global health threats. However, the combined neurotoxic effects of Pb and HTN, particularly in terms of mood disorders such as anxiety and depression, remain poorly understood. Herein, using a combined exposure model, we found co-exposure to Pb and HTN markedly aggravates anxiety- and depression-like behaviors in mice compared with Pb and HTN exposure alone. The prefrontal cortex was identified as the most vulnerable brain region, with astrocytes as the most susceptible cell type to senescence. Notably, treatment with dasatinib and quercetin, a senolytic regimen that selectively eliminates senescent cells, significantly alleviated the behavioral deficits induced by Pb and HTN co-exposure. Further investigation revealed Pb and angiotensin II (AngII) co-exposure promoted phase separation of cyclic GMP-AMP synthase (cGAS), a key DNA sensor. Pharmacological disruption of biomolecular condensates with 1,6-hexanediol (1,6-HD) partially rescued astrocyte senescence induced by Pb and AngII co-exposure. Inhibition of mitochondrial DNA (mtDNA) replication with ethidium bromide (EtBr) markedly reduced cytosolic mtDNA accumulation caused by co-exposure, suppressed cGAS phase separation, and downregulated the expression of senescence-associated proteins including P16, P211, γH2AX, and SASP. These findings uncover a previously unrecognized role of mtDNA-dependent cGAS phase separation in driving astrocyte senescence and environment-related neuropsychiatric dysfunction, and highlight cGAS phase separation as a promising therapeutic target for preventing anxiety and depression in individuals simultaneously exposed to Pb and HTN.

Source: https://pubmed.ncbi.nlm.nih.gov/42364866/

• PMID 42200669 (2026, Journal of virology) — Going wild: prioritizing experimental models of rodent-borne viruses to decode zoonotic spillover and pandemic risk.. Abstract (opening): Rodent-borne viruses pose threats to global health because of their capacity for zoonoses with the potential to cause outbreaks of high morbidity and mortality. Gaining a deeper understanding of how these viruses persist in their reservoir hosts and spillover into human populations requires an integrated approach blending both laboratory- and field-based research. Here, we review our current understanding of rodent-borne virus dynamics-primarily mammarenaviruses and orthohantaviruses-within their natural rodent reservoirs. We highlight key insights gained from experimental infection models seeking to replicate authentic host-pathogen interactions under controlled conditions. We argue that expanding and refining experimental models, particularly those that simulate natural reservoir conditions, is crucial to identifying the host and viral factors facilitating viral persistence in nature, and transmission to human populations. We propose a framework for future research that prioritizes hypothesis-driven research in model systems that are both natural and translatable to bridge these knowledge gaps.

Source: https://pubmed.ncbi.nlm.nih.gov/42200669/

• PMID 41392373 (2026, Basic & clinical pharmacology & toxicology) — Chelation Therapy for Rare Earth Element Toxicity: Current Evidence, Challenges and Future Directions.. Abstract (opening): The accelerating integration of rare earth elements (REEs) in advanced technologies has generated rising concern over human exposure and the attendant toxicological risks. This review presents an up-to-date synthesis of current evidence on REE toxicity across multiple exposure pathways, including inhalation, ingestion and occupational contact, providing an integrative perspective from human clinical data, animal models and in vitro systems. Distinct from traditional reviews, it critically appraises how REE-specific mechanisms, such as oxidative stress, mitochondrial dysfunction and metal ion substitution, produce multiorgan effects with clinical manifestations distinct from those of conventional heavy metals. A key novel finding is the pronounced therapeutic gap. Although chelation is well established for many toxic metals, effective chelation therapy for REE remains largely undeveloped, with current agents like DTPA showing limited efficacy, particularly for gadolinium and cerium, underscoring a major gap in clinical practice. The review highlights vital implications for clinicians, stressing the importance of early exposure recognition, tailored supportive care and the urgent development and validation of REE-specific chelators. Priorities for future research include creating novel chelation strategies and harmonizing international guidance to protect exposed populations. This synthesis aims to equip health professionals, toxicologists and policy-makers with actionable insight, emphasizing the clinical and regulatory urgency of increasing REE exposure and toxicity.

Source: https://pubmed.ncbi.nlm.nih.gov/41392373/

• PMID 42151291 (2026, Scientific reports) — Environmental and sustainable valorization of spent adsorbent: safety and acute toxicity evaluation in rats via probit analysis.. Abstract (opening): Valorization of adsorbent spent is a modern trend to maximize the utilization of absorption waste. Analytical methods, inclusive Fourier Transform Infra Red (FTIR) spectroscopy, Scanning Electron Microscope (SEM), and X-Ray Diffraction (XRD), were applied to evaluate the adsorbent spent (Zn-Co-Fe/LDH @ heavy metal). We examined the mechanistic toxicological effects of heavy metals within an animal model (rats) via probit analysis to evaluate the safety and acute toxicity of the spent adsorbent. The acute toxicity was evaluated and documented for 24 h, and it persisted for 14 days. A diverse multitude of toxic impacts on a different of body organs and tissues is the consequence of the bioaccumulation of these heavy metals. The rodents were weighed daily, and a variety of observations, like mortality, injury, behavior, and any indications of disease, were conducted. The safety and toxicological analyses were conducted using Probit analysis. The acute toxicity evaluation revealed varying safety profiles for the spent adsorbents. Zn-Co-Fe/LDH-As exhibited the lowest level of toxicity with an LD₅₀ of 370 mg/kg and a calculated safe dose of 18.5 mg/kg. In contrast, the highest toxicity was observed for Zn-Co-Fe/LDH-Pb (LD₅₀ = 103.7 mg/kg; safe dose = 5.2 mg/kg), followed by Zn-Co-Fe/LDH-Hg (LD₅₀ = 204 mg/kg; safe dose = 10.2 mg/kg). These results quantify the biological risk associated with metal-laden adsorbents and establish the safety benchmarks required for their sustainable valorization. Evaluations of biochemical parameters and hematological analysis were conducted at the conclusion of each investigation. Comparative to the controls, gross findings were obtained from the histopathological examination of the animals' vital organs, which included the heart, lung, kidney, liver, and stomach. Our safety and toxicological data demonstrated the safety of layered double hydroxide (LDH) efficacy in adsorption, as well as a lower level of toxicity for LDH/As after adsorption. The iron content within the Zn-Co-Fe/LDH framework remained structurally integrated; however, the observed hematological alterations suggest a potential interference with iron metabolism or heme synthesis following exposure to heavy-metal laden adsorbents.

Source: https://pubmed.ncbi.nlm.nih.gov/42151291/

• PMID 42224357 (2026, PloS one) — Dimercaprol (BAL): Insights into conformational stability, fragmentation pathways via tandem LR-ESI, HR-EI mass spectrometry, and gas-phase thermochemical properties from quantum chemical calculations.. Abstract (opening): Dimercaprol (British antilewisite, BAL) is a long-established chelating agent used in the treatment of heavy metal poisoning; however, its physicochemical and thermochemical properties have not yet been fully characterized. In this study, we combined gas-phase quantum chemical calculations with high-resolution mass spectrometry to investigate the conformational stability, fragmentation pathways, and thermochemical parameters of BAL. Fragmentation behavior was examined by gas chromatography/mass spectrometry-QTOF under electronic ionization conditions, and the resulting spectra were interpreted through proposed dissociation pathways involving water, hydrogen sulfide, and thiyl radical losses, supported by reaction enthalpies calculated at the theoretical level M06-2X/6-311++G(3df,3pd). Conformational analysis identified five low-energy structures (BAL-1 to BAL-5), where intramolecular hydrogen bonds and gauche/anti interactions play a key role in stability; BAL-3 was consistently predicted as the lowest-energy conformer. Vibrational frequencies calculated with the B3LYP, M06-2X, and MN15 functionals showed good agreement with experimental FTIR and Raman data. The thermochemical properties were further evaluated using Gn composite methods (G3MP2B3, G3B3, G4MP2 and G4) which yielded an average standard enthalpy of formation at ΔH°(f,298K) of -45.6 ± 1.1 kcal/mol. This work provides a detailed experimental and theoretical characterization of dimercaprol, providing information on its possible fragmentation mechanism and conformational landscape, and offering a thermochemical framework that could support future pharmacological, toxicological and environmental applications.

Source: https://pubmed.ncbi.nlm.nih.gov/42224357/

• PMID 42302541 (2026, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)) — Chronic intermittent hypobaric hypoxia ameliorates iron metabolism disorder through ferritinophagy in collagen-induced arthritis mice.. Abstract (opening): <h4>Aim</h4>Rheumatoid arthritis (RA) is a chronic inflammatory disease that is often complicated by anemia of chronic disease (ACD). Studies have shown that the development of ACD is closely related to iron metabolism disorder. Our previous studies have suggested that chronic intermittent hypobaric hypoxia (CIHH) treatment can improve iron metabolism disorder in obesity and metabolic syndrome rats. However, it is not known whether it affects the iron metabolism disorder caused by arthritis. Therefore, the aim of this study was to observe the effects of CIHH on erythrocyte index and iron metabolism in collagen-induced arthritis (CIA) mice model and to further explore the mechanism of ferritinophagy.<h4>Methods</h4>Eight-week-old male DBA/1 mice were randomly divided into four groups: control group (CON), chronic intermittent hypobaric hypoxia treatment group(CIHH, subjected to hypobaric hypoxia simulating 4000-m altitude for 35 days, 6 h daily), collagen-induced arthritis model group(CIA, injected intradermally in the tail with bovine type II collagen and complete Freund's adjuvant suspension), and CIA + CIHH group. During the experimental period, the body weights and joint scores of mice in each group were recorded every four days. A hematology analyzer was used to measure erythrocyte indexes (Red Blood Cell (RBC), Hemoglobin (Hb), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH)); serum iron (SI) was measured by micrometry; enzyme-linked immunosorbent assay (ELISA) was used to measure serum ferritin (SF) and soluble transferrin receptor (sTfR); the pathologic and histologic changes of mice knee joints were observed by hematoxylin-eosin staining (HE); ferrous ion concentration was detected by ferrous ion colorimetric test kit; Western blot was applied to detect the iron metabolism (transferrin receptor (TfR), ferroportin1 (FPN1)), divalent metal-ion transporter-1 (DMT1), ferritin heavy chain1 (FTH1))and ferritinophagy indicator (nuclear receptor coactivator 4 (NCOA4)); the application of co-immunoprecipitation (CO-IP) was applied to detect the level of ferritinophagy flux (NCOA4/FTH1).<h4>Results</h4>Compared with CON mice, CIA mice had significantly lower body weight, severer redness, swelling and deformation of joints, impaired erosion of bone tissues, lower erythrocyte indexes, increased hepatic iron deposition, disturbed iron metabolism parameters, in addition, the decreased expression of NCOA4 and ferritinophagy flux, which were all significantly improved after treatment with CIHH.<h4>Conclusions</h4>CIHH significantly ameliorated iron metabolism disorders in CIA mice, possibly by promoting NCOA4-mediated ferritinophagy and increasing iron release and export. This study provides new ideas for the prevention and adjuvant treatment of ACD.

Source: https://pubmed.ncbi.nlm.nih.gov/42302541/

• PMID 42472577 (2026, Biochemical pharmacology) — CYP2E1 inhibitor Q11 shows potential in alleviating cisplatin-induced acute kidney injury via mitigating mitochondrial dysfunction and modulating NF-κB pathway.. Abstract (opening): Cisplatin remains a major cause of acute kidney injury (AKI) and effective therapeutic strategies are still lacking. Cytochrome P450 2E1 (CYP2E1), a phase I metabolic enzyme, has been increasingly implicated in inflammatory disorders. This study aimed to investigate the therapeutic potential and underlying mechanisms of a novel CYP2E1 inhibitor, Q11, in cisplatin-induced AKI. The role of CYP2E1 in AKI was assessed using Cyp2e1 knockout rats, and the protective effects of Q11 were evaluated in a mouse model. Further mechanistic insights were gained through transcriptomic analysis and experiments in renal tubular epithelial cells. The results showed that CYP2E1 expression and enzymatic activity were significantly elevated in AKI animals. Knockout of Cyp2e1 markedly attenuated renal dysfunction and inflammation. Treatment with Q11 similarly improved survival, reduced serum creatinine and blood urea nitrogen levels, and alleviated renal histopathological damage in cisplatin-treated mice. Mechanistically, Q11 suppressed oxidative stress by reducing reactive oxygen species (ROS) and increasing glutathione levels, and also downregulated pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Transcriptomic and western blot analyses revealed that Q11 inhibited the nuclear factor kappa B (NF-κB) signaling pathway and restored mitochondrial function. In vitro studies further demonstrated that Q11 reduced CYP2E1 expression, improved mitochondrial membrane potential, and decreased apoptosis in human kidney-2 cells (HK-2) and mouse renal tubular epithelial cells (mRTEC). In conclusion, CYP2E1 plays a pivotal role in cisplatin-induced AKI, and the novel inhibitor Q11 exerts renoprotective effects by mitigating mitochondrial dysfunction and suppressing NF-κB-mediated inflammation.

Source: https://pubmed.ncbi.nlm.nih.gov/42472577/

• PMID 41884135 (2026, Frontiers in medicine) — Neurological impairment and hyperglycemia following acute copper sulfate poisoning: a case report.. Abstract (opening): <h4>Rationale</h4>Generally, clinical manifestations of copper sulfate intoxication include acute gastroenteritis, hemolytic anemia, and hepatorenal failure. Herein, we reported the case of a patient who developed neurological impairment and hyperglycemia following massive oral ingestion of copper sulfate. The article was to characterize these uncommon complications that extend beyond the typical toxicological spectrum, thereby enhancing the clinical understanding of copper sulfate toxicity.<h4>Patient concerns</h4>A 14-year-old girl ingested approximately 50 grams of copper sulfate. Following initial resuscitation at a local hospital, she developed rapidly progressive tachypnea and hypoxemia. She was immediately transferred to Jinhua Central Hospital for further treatment.<h4>Diagnosis</h4>The patient was diagnosed with acute severe copper sulfate intoxication, complicated by hemolytic anemia, hepatorenal failure, and two rare sequelae: neurological impairment and hyperglycemia.<h4>Interventions and outcomes</h4>The patient received gastric lavage with 15,000 mL of isotonic solution at a local hospital. Due to the subsequent deterioration of respiratory function (tachypnea and hypoxemia), she was transferred to our hospital. Based on experience from previously reported successful cases of copper sulfate poisoning, we immediately implemented a comprehensive therapeutic regimen, including plasma exchange, copper chelation therapy (sodium dimercaptopropane sulfonate combined with calcium disodium edetate), and continuous renal replacement therapy. During hospitalization, the patient developed epileptic seizures, lower extremity neurological impairment, and persistent hyperglycemia. After symptomatic treatment with neurotrophic agents and insulin for glycemic control, clinical manifestations improved, with no recurrence of epilepsy. However, hyperglycemia and lower extremity neurological dysfunction showed only partial remission and were not fully resolved at discharge.<h4>Lessons</h4>Acute massive copper sulfate poisoning may induce neurological impairment and hyperglycemia. Importantly, early monitoring and heightened vigilance for the delayed onset and protracted course of such complications are imperative.

Source: https://pubmed.ncbi.nlm.nih.gov/41884135/

• PMID 41907795 (2026, Risk management and healthcare policy) — Policy Evaluation for Regulating Toxic Traditional Chinese Medicines in Taiwan.. Abstract (opening): In recent years, growing reports of poisoning and adverse reactions linked to the misuse of traditional Chinese medicine (TCM) have raised increasing concerns about its safety. This article begins with the case of aristolochic acid nephropathy and draws on international regulatory practices to evaluate Taiwan's legal and policy framework governing toxic TCMs. The analysis reveals systemic deficiencies in the <i>Taiwan Herbal Pharmacopoeia</i> and related regulations, particularly in the classification of toxic substances, <i>Paozhi</i> (processing methods), and dosage safety standards. The article argues that the regulation of toxic TCMs should be grounded in scientific methodology and toxicological principles, incorporating risk assessment to establish rational toxicity classifications, standardized processing protocols, and usage restrictions, thereby enabling clinical practice to achieve the goal of high efficacy with low toxicity. It further advocates for the implementation of adverse event reporting mechanisms to safeguard public health.

Source: https://pubmed.ncbi.nlm.nih.gov/41907795/

• PMID 41893504 (2026, Toxics) — Dermal Exposure to Heavy Metals in Urban Green Space Soils: A Review of Bioavailability, Toxic Mechanisms, and Precision Risk Assessment.. Abstract (opening): Urban green spaces (UGSs) provide essential ecological services but also accumulate heavy metals (HMs) in their soils, posing a paradoxical health risk through dermal exposure. Traditional risk assessments, based solely on total HM concentrations, often overestimate threats by ignoring bioavailability (the fraction actually absorbed by organisms) and dynamic skin microenvironment factors. This review synthesizes recent advances to propose a precision assessment framework that integrates bioavailability. The framework advocates for the incorporation of bioaccessibility (the fraction of pollutants dissolved in body fluids)-driven exposure metrics (e.g., physiologically based extraction tests), mechanistic dermal permeation models (e.g., Franz diffusion cells, 3D skin constructs), and population-specific susceptibility factors (e.g., children, individuals with compromised skin). We elucidate how soil properties (pH, organic matter) and metal speciation (e.g., Cr(III)/Cr(VI)) modulate cutaneous uptake, and detail toxicological mechanisms including oxidative stress, ferroptosis/cuproptosis, immunotoxicity, and pigmentation disorders. Case studies reveal heterogeneous HM hotspots in high-traffic and densely populated areas, while in vitro-in vivo extrapolation highlights the potential for misestimation in traditional models. Consequently, we discuss the limitations and future directions of this framework, aiming to shift UGS risk management from over-conservative assessment to bioavailability-based precision governance, thereby supporting the health security of sustainable urban habitats.

Source: https://pubmed.ncbi.nlm.nih.gov/41893504/

• PMID 42080322 (2026, mAbs) — Structure-function analysis of empasiprubart, a calcium- and pH-dependent clinical phase complement C2 blocking antibody.. Abstract (opening): Empasiprubart (ARGX-117) is a humanized recycling antibody that prevents binding of C2 to C4b, blocking downstream classical and lectin pathways of complement activation. Empasiprubart binds to the CCP2 domain of complement component C2 in a calcium- and pH-dependent manner, leveraging physiological differences between blood and endosomal environments to facilitate the release and subsequent degradation of bound C2. The molecule incorporates Fc region mutations (H433K and N434F) that enhance its affinity for the neonatal Fc receptor (FcRn) under acidic endosomal conditions, thereby prolonging its <i>in vivo</i> half-life and supporting its recycling capacity. However, despite the earlier description of the complex structure, the molecular mechanism underlying these dependencies has remained elusive. Here, we further explored the crystal structure of the empasiprubart fragment antigen-binding (Fab) complexed to a C2 fragment, and provide a molecular rationale for its unique properties, while recognizing that not all contributing factors have been fully elucidated. Our observations indicate that the pH-dependent target release is rooted in a subtle intramolecular complementarity-determining region (CDR) destabilization, rather than direct modulation of the binding interface, and highlight the interplay between framework residues and CDRs. Collectively, our results not only lead to a better understanding of the mode of action of empasiprubart but also demonstrate the pivotal role of framework residues in the orchestration of antibody CDR function for non-trivial target binding.

Source: https://pubmed.ncbi.nlm.nih.gov/42080322/

Source text: pdf-raw/evidence/europepmc_rat_mouse_toxicology_2026-08-01.txt (Europe PMC first-hand abstracts, pulled 2026-08-01).