Evidence cluster — Rabbit (Oryctolagus cuniculus) toxicology (peer-reviewed, Europe PMC)

Evidence: Rabbit (Oryctolagus cuniculus) 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 Oryctolagus cuniculus. The cluster returns 12 representative studies with abstracts below. Abstract text is verbatim from source; each study is traceable by PMID.

Studies

• PMID 42341106 (2026, Science advances) — Common human ALDH1B1 and ALDH2 variants increase neuroinflammatory response to a single ethanol dose in mice.. Abstract (opening): Unlike the well-documented effects of aldehyde dehydrogenase 2 (ALDH2) hypoactive variants, the impact of hypoactive ALDH1B1 has yet to be elucidated. Using the Global Human Genome Aggregation Database, we identified 38 ALDH1B1 variants, common (>0.1% allele frequency) to different human genetic ancestral groups. Some missense ALDH1B1 human variants are notably less active and less stable, and three variants represent a complete loss of function (LoF) due to early stop codon. Since these inactive variants are common among humans, we studied the impact of carrying both ALDH1B1 LoF and ALDH2 inactive variant in mice. Double knock-in (DKI) mice carrying ALDH1B1^G193fs and ALDH2*2^E504K exhibited elevated neuroinjury markers. Following a single ethanol gavage (2 grams per kilogram), DKI mice showed exacerbated intoxication and significantly higher levels of neuroinjury markers, including elevated amyloid-β and ptau217 compared to WT or single-mutant mice. Our study highlights a potential impact of common hypoactive mitochondrial ALDH enzymes on human health, especially among those that consume alcohol.

Source: https://pubmed.ncbi.nlm.nih.gov/42341106/

• PMID 42346410 (2026, Metabolites) — Metabolic Mechanisms of Hexavalent Chromium-Induced Splenic Immune Injury via Oxidative Stress and Ferroptosis Pathways in New Zealand Rabbits.. Abstract (opening): <b>Background</b>: Hexavalent chromium (Cr(VI)) is a widespread environmental toxic heavy metal with strong oxidative properties; however, its immunotoxicity and metabolic mechanisms in rabbit spleen remain largely unclear. <b>Methods</b>: In this study, New Zealand rabbits were exposed to 0, 12.5, 25, and 50 mg/L Cr(VI) (as potassium dichromate, K₂Cr₂O₇) via drinking water for four weeks to investigate splenic damage and the underlying molecular pathways. Spleen pathological injury was evaluated by hematoxylin and eosin (H&E) staining, and the distribution of T cells, B cells, and macrophages was assessed by immunohistochemistry. Antioxidant enzyme activities and antioxidant substance levels were determined using ELISA, and the relative mRNA expression of immune factor genes, antioxidant-related genes, and ferroptosis-related genes was quantified by quantitative real-time PCR (qRT-PCR). In addition, the distribution of iron in splenic tissue was detected by enhanced Prussian blue staining. <b>Results</b>: Our results demonstrate that high-dose Cr(VI) significantly inhibited body weight gain, induced lymphocyte atrophy, vacuolization, and widening of intercellular spaces in the splenic white pulp. Furthermore, Cr(VI) reduced T and B lymphocyte populations, promoted macrophage infiltration and inflammatory cytokine gene expression in a concentration-dependent manner, impaired total antioxidant capacity, and led to a decrease in glutathione (GSH) levels in the spleen. Additionally, Cr(VI) exposure increased iron accumulation, activated the ACSL4-NOX lipid peroxidation cascade, and downregulated <i>GPX4</i> expression, ultimately triggering ferroptosis. <b>Conclusions</b>: These findings reveal that Cr(VI) causes splenic immune injury by disrupting oxidative homeostasis and inducing ferroptosis, providing novel insights for evaluating immunotoxicity and identifying metabolic targets under Cr(VI) pollution.

Source: https://pubmed.ncbi.nlm.nih.gov/42346410/

• PMID 42149351 (2026, Cardiovascular toxicology) — Cardiac Electrophysiologic Effects of Different Local Anesthetics in Langendorff-Perfused Rabbit Hearts.. Abstract (opening): Local anesthetics are widely used in medical care. However, their sodium channel blocking properties not only explain their analgesic potency but also their possible cardiotoxic effects. Due to the different pharmacodynamics and pharmacokinetics of different local anesthetics as well as the divergent cellular electrophysiological effects, we aimed to investigate and compare the electrophysiological effects of different local anesthetics in an established Langendorff model of the isolated rabbit heart. 50 hearts of New Zealand White rabbits were retrogradely perfused employing a Langendorff-setup. Eight catheters were placed endo- and epicardially, thereby recording monophasic action potentials. Hearts were paced at seven different cycle lengths (300-900 ms), thus obtaining cycle-length dependent action potential duration at 90% of repolarization (APD₉₀), QT intervals and dispersion of repolarization. In addition, burst pacing was utilized to assess ventricular vulnerability. Thereafter, bradycardic AV-blocked hearts were perfused with a hypokalemic solution to enhance the occurrence of triggered activity. After generating baseline data, the hearts were assigned to four groups: In group 1, hearts were treated with 25 µM, and 50 µM lidocaine. Group 2 was perfused with 25 µM, and 50 µM mepivacaine. Group 3 was perfused with 0.5 µM, and 1 µM bupivacaine. Group 4 was perfused with 5 µM, and 10 µM ropivacaine. As expected, perfusion with all local anesthetics led to a significant prolongation of the effective refractory period as a result of sodium channel blockade. Perfusion with bupivacaine and ropivacaine resulted in pronounced cardiotoxic effects, characterized by electromechanical uncoupling or loss-of-capture phenomena, in the majority of hearts. Perfusion with mepivacaine and ropivacaine resulted in the comparatively most pronounced prolongation of the effective refractory period. Accompanied by a pronounced dispersion of repolarization, the highest incidence of ventricular tachycardia and ventricular fibrillation episodes was observed during perfusion with bupivacaine. Perfusion with the local anesthetics showed pronounced electrophysiological effects, which differed between the various local anesthetics. Bupivacaine showed the most pronounced cardiotoxic effects even at low doses.

Source: https://pubmed.ncbi.nlm.nih.gov/42149351/

• PMID 41938863 (2026, Frontiers in cellular and infection microbiology) — TM9SF4 acts as a receptor mediating &lt;i&gt;Glaesserella parasuis&lt;/i&gt; cytolethal distending toxin-induced cytotoxicity in PK15 cells.. Abstract (opening): <h4>Background</h4>Cytolethal Distending Toxin (CDT) is the only exotoxin that <i>Glaesserella parasuis</i> (<i>G. parasuis</i>) can secrete. <i>G. parasuis</i> CDT (<i>Gp</i>CDT) triggers DNA damage responses, leading to irreversible cell cycle arrest and apoptosis, playing an important role in the pathogenic process of <i>G. parasuis</i>. Currently, research on the host cell receptors of <i>Gp</i>CDT remains limited. Screening and identification of host cell receptors that interact with <i>Gp</i>CDT are crucial for systematically elucidating the cytotoxic mechanisms induced by this toxin.<h4>Methods</h4>This study employed Co-immunoprecipitation (Co-IP) combined with Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) to identify potential host proteins interacting with <i>Gp</i>CDT in PK15 cells. Nine Proteins were selected for further evaluation based on subcellular localization and Gene Ontology classification. Eukaryotic expression and Co-IP validated four interacting proteins. Subsequently, heterozygous knockout PK15 cell lines for these genes were generated via CRISPR/Cas9, and CCK-8 assays identified TM9SF4 as having the most significant impact on <i>Gp</i>CDT virulence. Therefore, a homozygous <i>TM9SF4</i> knockout PK15 cell line (KO) was generated via limited dilution, and a stable <i>TM9SF4</i>-overexpressing PK15 cell line (OE) was established through lentiviral packaging. Western blotting and qRT-PCR confirmed protein and gene expression, and CCK-8 assays combined with cytopathic effect (CPE) observation determined the role of TM9SF4 in <i>Gp</i>CDT-induced cytotoxicity. Finally, indirect immunofluorescence was performed to assess co-localization of TM9SF4 with <i>Gp</i>CDT.<h4>Results</h4>We identified 287 proteins in PK15 cells that potentially interact with <i>Gp</i>CDT, among which 58 were localized to the plasma membrane or extracellular. Nine proteins were selected for further investigation. Among them, EPHB4, LITAF, TM9SF4, SLC12A4 interacted with <i>Gp</i>CDT, but only the deficiency of TM9SF4 significantly inhibited the virulence of the <i>Gp</i>CDT. Results from CCK-8 and CPE showed that KO cells exhibited significantly higher survival rates and suppressed <i>Gp</i>CDT-induced cellular distention and cell death, whereas OE cells showed decreased survival rates and typical cytopathic change. Finally, indirect immunofluorescence confirmed strong co-localization between TM9SF4 and <i>Gp</i>CDT.<h4>Conclusion</h4>We initially proposed TM9SF4 as a receptor for <i>Gp</i>CDT in PK15 cells, essential for <i>Gp</i>CDT binding and cytotoxicity. This study may provide a new theoretical basis for targeted prevention and treatment of swine Glässer's disease.

Source: https://pubmed.ncbi.nlm.nih.gov/41938863/

• PMID 41789561 (2026, Journal of chemical information and modeling) — Integrating Multiview Information for Enhanced Deep Learning-Based Acute Dermal Toxicity Prediction.. Abstract (opening): Accurate prediction of acute dermal toxicity is vital for the safe and effective development of contact drugs. While numerous deep learning models have been created to replace costly and ethically challenging animal toxicity tests, most approaches overlook the multiview information on molecules. To overcome this limitation, we introduce a novel model named MVIToxNet, which integrates multiview features from both molecular fingerprints and SMILES sequences. To capture the multiview information on SMILES, MVIToxNet incorporates character-level and atom-level features. In addition, byte-pair encoding tokenization is utilized to capture substructural details within molecules, allowing the model to differentiate similar SMILES by assigning distinct tokens to different substructures. Since the data sets in this study are small and imbalanced, we argue that selecting a single model based solely on the best validation performance may not reliably reflect the best generalization for test sets. Therefore, we propose a weighted model averaging approach that combines multiple trained models according to their top-K validation scores into one model, yielding an improved model for inference. Extensive experimental results demonstrate that MVIToxNet significantly outperforms existing baselines in acute dermal toxicity prediction, validating the effectiveness of utilizing multiview features and the weighted model averaging strategy. Furthermore, our proposed methods demonstrate the potential for data-driven model design.

Source: https://pubmed.ncbi.nlm.nih.gov/41789561/

• PMID 42123454 (2026, International journal of molecular sciences) — The Synthetic Cannabinoid AKB-48 Induces Cell Death in Murine Cerebellum Through Different Signaling Pathways.. Abstract (opening): Novel psychoactive substances (NPSs) exhibit extremely strong pharmaco-toxicological activity, often leading to severe adverse effects that pose a serious risk to consumers' health. Among these, synthetic cannabinoids (SCs) currently represent the majority of drug seizures in Europe. One such compound, AKB-48 (also known as APINACA), was first identified in Japanese herbal smoking blends in 2012. Although it mimics the effects of Δ9-THC, the primary psychoactive component of <i>Cannabis sativa</i>, AKB-48 can induce more severe and potentially life-threatening outcomes. Several in vivo studies investigating the acute administration of AKB-48 have reported profound behavioral, neurological, and neurochemical alterations, including disruptions of neurotransmission across multiple brain regions, thus confirming its neurotoxic potential. Given the recognized vulnerability of the cerebellum to NPS, and its critical role in integrating neural circuits affected by psychostimulant drugs, the present study evaluated the toxic effects of repeated AKB-48 exposure on the cerebellar cortex of adult male and female ICR-CD1^® mice. Particular attention was paid to the modulation of cell death pathways, alongside assessments of sensorimotor responses. The results demonstrate, for the first time, that repeated AKB-48 administration induces significant morphological, immunohistochemical, and ultrastructural changes in both male and female mice. These alterations included pronounced disruption of cerebellar architecture and marked modulation of cell death pathways, further corroborated by TEM-detected ultrastructural damage and a substantial reduction in the basal visual placing response. Overall, the findings provide clear evidence of AKB-48's sex-independent neurotoxicity, leading to cerebellar alterations that ultimately result in neuroplasticity impairment.

Source: https://pubmed.ncbi.nlm.nih.gov/42123454/

• PMID 42305710 (2026, Experimental and therapeutic medicine) — Integrated network pharmacology and serum metabolomics to reveal the protective mechanism of methanolic extract of BaiYangJie on cisplatin-induced acute kidney injury in mice.. Abstract (opening): Cisplatin, a chemotherapeutic drug, produces severe nephrotoxicity and at present, there are no effective drugs to clinically prevent or treat it. In the Dai nationality, BaiYangJie is used to treat poisoning caused by chemicals or drugs. Previous research has demonstrated that the methanolic extract of BaiYangJie (MEAG) can treat cisplatin-induced nephrotoxicity; however, its mechanism of action remains unclear. The aim of the present study was therefore to identify the potential mechanism of action of MEAG in cisplatin nephrotoxicity using a combination of network pharmacology and serum metabolomics. Initially, network pharmacology analysis was used to identify hub targets and signalling pathways involved in the renoprotective effects of MEAG. Subsequently, plasma metabolomics profiling utilising ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology revealed key metabolic alterations and pathway modulations associated with MEAG treatment. Finally, integrated analysis uncovered key molecular mechanisms, which were subsequently validated by western blotting and immunohistochemistry. A total of 13 endogenous metabolites were identified in serum metabolomics, primarily involved in phenylalanine metabolism and in the biosynthesis of phenylalanine, tyrosine and tryptophan. The treatment of MEAG in cis-induced acute kidney injury primarily involved regulating the inflammatory response, responses to lipid and chemical stress, the FoxO signalling pathway, arachidonic acid metabolism and the NF-κB signalling pathway. Animal experiments showed that MEAG can inhibit inflammation and the expression of the migration inhibitory factor (MIF)/NF-κB pathway. Through integrated network pharmacological analysis, metabolomic profiling and experimental validation, it was systematically elucidated that MEAG exerted its therapeutic effects through dual regulatory mechanisms: Suppressing inflammatory responses by inhibiting overactivation of the MIF/NF-κB signalling pathway and restoring phenylalanine metabolic homeostasis. These findings thus provide a mechanistic foundation for developing targeted therapeutic strategies against chemotherapy-associated nephrotoxicity.

Source: https://pubmed.ncbi.nlm.nih.gov/42305710/

• PMID 42487466 (2026, Journal of applied toxicology : JAT) — Electrophysiological Characterization of MK886-Mediated Suppression of Voltage-Gated K&lt;sup&gt;+&lt;/sup&gt; Currents in Rabbit Coronary Artery Smooth Muscle Cells.. Abstract (opening): MK886 is a selective inhibitor of 5-lipoxygenase-activating protein that suppresses leukotriene synthesis and improves vascular reactivity in rabbit models of endotoxic shock. However, its direct effects on vascular voltage-gated K⁺ (Kv) channels remain unclear. In this study, we used the whole-cell patch-clamp technique to investigate the electrophysiological actions of MK886 on Kv currents in rabbit coronary artery smooth muscle cells. MK886 inhibited Kv currents in a concentration-dependent manner, with an IC₅₀ of 0.51 ± 0.23 μM and a Hill coefficient of 0.9 ± 0.14 (n = 8). While steady-state activation was not significantly affected, MK886 induced a pronounced leftward shift in the steady-state inactivation curve, implying preferential binding to the inactivated state of the channel. Consistent with this interpretation, it produced use-dependent inhibition during repetitive depolarizing pulses at 1 and 2 Hz and significantly slowed recovery from inactivation. Pharmacological dissection using subtype-selective Kv channel inhibitors revealed that the MK886-induced inhibition was reduced in the presence of DPO-1, stromatoxin-1, and linopirdine compared with MK886 alone. The reduction was more pronounced under DPO-1 and stromatoxin-1 conditions, suggesting that Kv1.5- and Kv2.1-related components may contribute to MK886-induced Kv current inhibition, with possible involvement of Kv7-related components to a lesser extent. In conclusion, MK886 directly suppresses rabbit coronary artery Kv currents in a concentration- and state-dependent manner by modulating inactivation gating, with substantial involvement of Kv1.5- and Kv2.1-related channel components and possible contribution of Kv7-related components.

Source: https://pubmed.ncbi.nlm.nih.gov/42487466/

• PMID 42185944 (2026, Addiction science & clinical practice) — Recognising intoxication in healthcare: evidence, challenges, and implications.. Abstract (opening): Intoxication is a common clinical presentation and is associated with increased risk of injury, self-harm, and premature mortality. It also complicates clinical care because patients who are intoxicated may provide unreliable histories, display altered pain perception, and exhibit behaviours that increase risk to themselves or others. Despite these challenges, research consistently shows that clinicians are often inaccurate in identifying intoxication or estimating its severity. This narrative review synthesises the literature on clinician recognition of alcohol and other drug intoxication to identify challenges that contribute to misclassification, and potential solutions to identifying intoxication in healthcare settings. Misclassification is most common at mild and moderate levels, where behavioural signs are subtle and easily masked by individual variability, tolerance, or co-occurring conditions. Severe intoxication is generally recognised more reliably, but this provides limited support for early risk detection or safe decision-making across the full clinical spectrum. Structured assessment tools have been developed to improve consistency, yet most show weak relationships with biological measures, have limited applicability across substance types, or have poor feasibility in routine practice. No widely adopted clinical tool exists, and accuracy does not consistently improve with professional experience or seniority. Evidence on the detection of non-alcohol substance intoxication in healthcare settings remains limited. Most available data comes from law enforcement contexts, where structured procedures and extensive training improve performance. These approaches do not translate easily to healthcare environments characterised by rapid patient turnover, competing demands, and limited capacity for lengthy assessments. Clinicians therefore continue to rely primarily on observational judgement, even though behavioural cues vary substantially and are prone to bias. This review integrates findings across alcohol and other drug classes, identifies common sources of perceptual and decision error, and outlines the implications of misclassification for patient safety, informed consent, diagnostic accuracy, and service utilisation. Improving recognition of intoxication will require investment in clinician training, development and validation of practical assessment tools, and targeted research examining accuracy across diverse clinical contexts. These steps are essential for safer and more consistent responses to intoxication in healthcare.

Source: https://pubmed.ncbi.nlm.nih.gov/42185944/

• PMID 41756586 (2026, Frontiers in veterinary science) — Temperature-responsive hydrogel of oclacitinib maleate administered via the rectum in rabbit.. Abstract (opening): <h4>Background</h4>The extensive and intense itching caused by skin diseases can significantly diminish the quality of life for companion animals. Oral administration of oclacitinib maleate is recognized as an important treatment for alleviating itching. Oral medications are affected by the animal's temperament and swallowing ability.<h4>Methods</h4>In this study, we developed a temperature-responsive hydrogel containing oclacitinib maleate for rectal administration, and we evaluated its therapeutic potential for treating itching through pharmacokinetic analysis using rabbits as test subjects.<h4>Results</h4>Pharmacokinetic results indicated that the transrectal administration of OM T-R Hydrogel effectively increased the blood concentration of oclacitinib maleate (T_max = 87 min, C_max = 37 ng/mL, t_1/2λz = 762 min). Furthermore, the OM T-R Hydrogel demonstrated no rectal mucosal irritation, confirming its safety for clinical use.<h4>Conclusion</h4>In conclusion, this paper successfully investigated a promising novel drug delivery system to alleviate pruritus in dogs and cats.

Source: https://pubmed.ncbi.nlm.nih.gov/41756586/

• PMID 41594534 (2026, Animals : an open access journal from MDPI) — Encephalitozoonosis in Pet Rabbits: Epidemiology, Pathogenesis, Immunology and Consensus on Clinical Management.. Abstract (opening): Members of the microsporidial genus <i>Encephalitozoon</i> have the capacity to infect both mammals and birds, and <i>E. cuniculi</i> is most commonly found in rabbits. With a seroprevalence ranging up to 85%, <i>E. cuniculi</i> can be a problem in pet rabbits as well as in food production and laboratory animal science. While most infections are likely subclinical, there are three main clinical presentations: neurological, renal, and ocular. Typical clinical signs including vestibular disease and phacoclastic uveitis may develop with initial or relapsing infection, while renal infection is usually progressive and associated with non-specific clinical signs. High-sensitivity/specificity ante mortem diagnostic options are lacking, and serological testing most often provides adjunct rather than definitive information such that physical examination and other diagnostics are used more so for ruling out other differentials and comorbidities, rather than confirming infection. In the veterinary community, treatment regimens are variable given the lack of thorough studies and a consensus. The aim of this document is to present the available literature to give a concise review of this organism and its infection of rabbits as well as to propose guidelines and protocols for diagnostics and treatment regimens. In addition, the current challenges and recommendations for further studies are discussed.

Source: https://pubmed.ncbi.nlm.nih.gov/41594534/

• PMID 42193971 (2026, Biomolecules) — Calretinin and Parvalbumin Trapping of TDP43 and XRCC1 Instructs Neocortical Interneuron Death in Neonatal Hypoxic-Ischemic Encephalopathy.. Abstract (opening): We examined neocortical pathology and interneuron degeneration in neonatal hypoxia-ischemic encephalopathy (HIE). Piglets in two age groups (2-3 or 7-10 days old, n = 4-12/group) underwent global cerebral hypoxia-ischemia (HI) or sham treatment. Piglets (2-3 days old) had epidural electrodes for continuous electroencephalography (cEEG) and were treated with hypothermia (HT) or remained at normothermia (NT). Older piglets, all NT, had scalp EEG. Piglets at both ages had seizures and survived for 1-7 days. Cortical damage was assessed by hematoxylin & eosin staining and immunohistochemistry; calretinin (CR), parvalbumin (PV), and vasoactive intestinal peptide (VIP) interneurons (INs) were counted. Cell injury was assessed by DNA fragmentation and protein nitration. TAR DNA binding protein-43 (TDP43) and the DNA repair scaffold protein X-ray repair cross complementing-1 (XRCC1) were examined for degeneration mechanisms. Cortical layers 3 and 4 showed high vulnerability; damage emerged as isolated cells, focal and laminar, and distributed as panlaminar throughout different cortical regions that correlated with seizure burden. HT protected strongly against cortical damage. CR- and PV-INs were severely depleted in HI-NT piglets compared to sham. VIP INs appeared invulnerable. HT partially rescued the loss of INs. CR and PV formed nuclear and cytoplasmic inclusions that colocalized with TDP43 and XRCC1; co-immunoprecipitation identified interactions among these proteins, and tyrosine nitration of CR. CR and PV INs accumulated DNA single- and double-strand breaks and appeared as attritional apoptosis variants with proteinopathy. This cell death is identified as aggreosis. IN loss correlated with seizure presence. Postmortem human neonatal HIE cases had a similar loss of CR and PV INs and nuclear depletion of TDP43 in the neocortex. Thus, neonatal HIE causes the loss of neocortical inhibitory IN subtypes with vulnerabilities instructed by their intrinsic calcium-binding protein signature and by mechanisms consistent with toxic sequestration and the nuclear depletion of XRCC1 and TDP43 underlying DNA damage accumulation. Early inhibitory IN deletion could drive seizure evolution in HIE; TDP43 and XRCC1 could be therapeutic targets for neonatal HIE.

Source: https://pubmed.ncbi.nlm.nih.gov/42193971/

Source text: pdf-raw/evidence/europepmc_rabbit_toxicology_2026-08-01.txt (Europe PMC first-hand abstracts, pulled 2026-08-01).