Toxicology Research最新文献

The hippocampus executes the integration of memory and spatial learning information. This study evaluated the effect of rice bran extract (RBE) on heavy metal mixture (MM) induced hippocampal toxicity and its underlying mechanism in albino rats. Thirty five rats were exposed to MM alone at Pb 20 mg/kg, Al 35 mg/kg, and Mn 0.564 mg/kg body weight or co-exposed with RBE at 125, 250 and 500 mg/kg body weight, 125 RBE mg/kg b.wt only, and 500 RBE mg/kg b.wt only 5 days a wk for 13 wk (90 days). Subsequently, oxidative stress, inflammation (cyclooxygenase-2) and caspase-3, amyloid precursor proteins (Aβ40 and Aβ42), HMOX-1, occludin and BDNF and transcription factor Nrf-2 in the hippocampus were investigated. MM treatment resulted in significantly higher escape latency time than both the control and MM plus RBE group. MM exposure induced increased oxidative stress, inflammation resulting in enhanced hippocampal apoptosis. MM significantly increased bioaccumulation of Pb, Al, and Pb; increased caspase-3, Nrf-2, Aβ40 and Aβ42 and significantly decreased occludin, BDNF, HMOX-1 when compared with the control. All these effects were reversed by RBE. Collectively, RBE ameliorated MM - induced oxidative stress, neuro-inflammation and hippocampal apoptosis via attenuation of oxidative damages of cellular constituents, neuronal inflammation and subsequent down regulation of amyloid precursor proteins Aβ40, Aβ42 and up regulation of occludin, BDNF, HMOX-1 protein expression via Nrf-2 dependent pathways to abrogate hippocampal toxicity associated with spatial learning and memory deficits.

Although intensive care unit (ICU) admission is the cornerstone in management of critically acute poisoned patients, the decision of ICU admission is often challenging, especially with limited resources. Hence, our study aimed to assess predictive models of the impact of ICU admission on outcomes of patients with acute poisoning. This retrospective cohort study recruited records of acutely poisoned patients admitted to Tanta University Poison Control Center between 2021 and 2023. Patient demographic and toxicological data, as well as initial clinical and laboratory profiles, were retrieved. Afterward, patients were categorized according to mortality and complicated outcomes. Out of 221 acutely poisoned patients admitted to the ICU, the incidences of mortality and complications in survivors were 54.3% and 57.4%, respectively. Aluminum phosphide (ALP) was the most common cause of poisoning (59%), with a significant association with mortality and predominance in cardiac complications. However, respiratory and neurological complications were evident among illicit substances, cholinesterase inhibitors, and neuropsychiatric drugs. The model anticipating morality included time from presentation to ICU admission, mean arterial pressure (MAP), oxygen saturation, pH, and ALP poisoning. Furthermore, the complication predictive model comprised time from exposure to poison center presentation, time from presentation to ICU admission, and MAP. Both models exhibited good to excellent discrimination performance and consistent calibration. Accordingly, prompt admission of all ALP-poisoned patients to ICU with a highly standardized level of care may alleviate their deleterious outcomes. However, drug categories with reversible courses should be adequately treated with frequent respiratory and hemodynamic monitoring in less-equipped ICUs.

In this study, zinc oxide nanoparticles (ZnO NPs) were obtained by green synthesis method using extracts prepared from Mentha pulegium L. species in order to investigate the cytotoxic, genotoxic and antimicrobial activities of nanoparticles. For the characterization of these nanoparticles, UV-Vis spectrophotometer, FT-IR, XRD and SEM analysis methods were used. For cell culture studies were carried out to determine the cytotoxic and genotoxic activities of ZnO NPs obtained by green synthesis with A549 cell line, which is a lung cancer cell. In the genotoxicity results determined by the Comet method, the highest DNA damage was seen at a concentration of 3.75 mg/mL. The genotoxic activity of different concentrations (0.1, 1, 5, 10 mM) of ZNO NPs were evaluated with SMART assay on Drosophila melanogaster. According to results ZNO NPs applications were found to be similar to the control group in all doses. On the other hand, in order to determine the antimicrobial activity, Escherichia coli (ATTC 25922), Staphylococcus aureus (ATTC 29213), Candida albicans (ATTC 90028), Klebsiella pneumoniae (ATTC 700603) and Salmonella enteritidis (ATTC 13076) microorganisms were cultured and disc diffusion test method was applied. In the disc diffusion test, dose application was made in the range of 15.6-500 mg/mL concentrations and it was observed that inhibition zone was formed at all concentrations.

This study was designed to adjust effective chemotherapy doses of cabazitaxel (CBZ) on cognitive behaviors, inflammatory cytokines and oxidative stress parameters, and survival rate in C6-induced GBM of rats. Male Sprague-Dawley rats bearing intra-caudate nucleus (CN) C6 inoculation were randomly divided into nine groups as follows: sham, tumor, Temozolomide (TMZ) vehicle, TMZ, CBZ vehicle, CBZ at doses of 0.5, 1, 2 and 4 mg/kg. Behavioral tests survival rate, histopathology, immunohistochemistry, oxidative stress, and inflammatory cytokines were evaluated. All drug treatments reduced the volume and number of tumor cells dose-dependently and CBZ4 was able to cause the greatest reduction. The %Survival rate of animals using CBZ1 significantly increased compared to other treatment groups. CBZ1 reduced anxiety-like behaviors and increased the balance of the animal with GBM. CBZ1 and CBZ2 groups improved C6-induced learning disabilities. Treatments could ameliorate tumor-induced dysregulation of oxidative stress. TNF-α/IL-10 decreased in the CBZ1 group compared to other treatment groups, which may indicate an improvement in inflammatory balance. Our findings demonstrate that the administration of CBZ at a dosage of 1 mg/kg exerts advantageous impacts on both the survival rate and neurocognitive performance of rats within the GBM model. However, our results showed that CBZ may have toxic effects, especially in a dose of 4 mg/kg.

Astragaloside IV (AS-IV), a major bioactive component of Astragalus membranaceus, exhibits anti-cancer and anti-inflammatory properties. However, its precise role in nasopharyngeal carcinoma (NPC) remains unclear. This study investigated the effects of AS-IV on NPC progression and its relationship with Special AT-rich binding protein-2 (SATB2), a diagnostic marker for NPC. AS-IV treatment reduced NPC cell viability in a dose-dependent manner, as assessed by CCK-8 assays. Functional experiments, including transwell, immunofluorescence, and flow cytometry assays, demonstrated that AS-IV inhibited cell migration, invasion, and autophagy while promoting apoptosis. Western blot analysis showed that SATB2 expression was significantly elevated in NPC cells, particularly in C666-1 and HK-1 cells. Overexpression of SATB2 partially reversed AS-IV's inhibitory effects on NPC progression. Further analysis revealed that AS-IV suppressed the Wnt signaling pathway by downregulating SATB2 expression, while SATB2 overexpression restored Wnt pathway activation. This effect was reversed upon treatment with the Wnt pathway inhibitor DKK-1. In vivo, AS-IV administration inhibited tumor growth in a nude mouse subcutaneous xenograft model, reduced Ki-67 positivity, and lowered LC3B expression, indicating decreased proliferation and autophagy. However, these effects were diminished upon SATB2 overexpression. These findings suggest that AS-IV exerts anti-tumor effects in NPC by downregulating SATB2 and suppressing Wnt pathway activation, highlighting its potential as a therapeutic agent for NPC.

Highlights: Astragaloside IV (AS-IV) reduces nasopharyngeal carcinoma (NPC) cell vitality, suppresses cell migration, invasion and autophagy, and fosters apoptosis.SATB2 exhibits notably high levels in NPC cells.Overexpression of SATB2 counteracts the inhibition of NPC malignant progression by AS-IV.AS-IV impedes NPC progression by decreasing SATB2 and thereby hindering the Wnt pathway.AS-IV deters NPC tumor growth in nude mice.

Adoption of a blood microsampling technique can reduce or avoid the use of satellite animals (rodents) for toxicokinetics or other purposes in discovery and toxicology studies and provides refinements applicable for both rodents and larger animals. Microsampling can increase the scientific value of data obtained from rodent studies during drug and (agro)chemical development, enabling multiple endpoints to be investigated and compared in an individual animal in the same way as non-rodents. A cross-sector survey was developed to understand the current use of microsampling in toxicology studies, with the aim of identifying the specific studies in which microsampling was employed and the barriers to wider uptake. A high proportion of the survey responses indicated that microsampling was used, however, the extent varied widely. Some organisations use the technique only in non-GLP studies. Microsampling was used most for pharmacokinetics or toxicokinetics, commonly within small molecule and agrochemical toxicity studies, but less frequently within large molecule, cell/gene therapies or industrial chemical studies. A wide variety of barriers to wider use of microsampling were provided, typically around reticence to change from using larger samples, or not wishing to validate another bioanalytical method given the resources and challenges associated with the validation of a new technology. Despite these barriers, some organisations have adopted microsampling routinely across many/all rodent toxicity studies and there are opportunities to further reduce and refine animal use across all sectors by wider adoption of microsampling.

This study investigated the protective effects of aqueous extracts of Asparagus officinalis and Corn Silk (Stigma maydis) against formaldehyde-induced reproductive toxicity in male albino rats. High-Performance Liquid Chromatography (HPLC) analysis revealed that Gallic acid was the major phenolic component in Corn Silk, while Syringic acid predominated in A. officinalis. Formaldehyde exposure significantly reduced (P < 0.05) body and testicular weights, reproductive hormone levels, sperm count, motility, and normal sperm morphology. It also caused notable histological changes and downregulated fertility-related genes (CDK2, Spem1, Fbxo47, and Tet1). Treatment with the plant extracts, especially at higher concentrations, significantly (P < 0.05) reversed these adverse effects, improved antioxidant status, and reduced tumor necrosis factor-α levels. These findings emphasize the potential applications of A. officinalis and Corn Silk extracts as natural toxicological agents, particularly for mitigating formaldehyde-induced reproductive toxicity. Additionally, their prospective role in fertility treatment underscores their potential to support reproductive health through natural, plant-based interventions.

Royal Jelly (RJ), a traditional medicinal compound with tumor-suppressive properties, was investigated for its antitumor effects on non-small cell lung cancer (NSCLC) using a mouse xenograft model. Fifty athymic nude mice were divided into five groups: a control group, an untreated NSCLC group, a doxorubicin (DOX)-treated group, an RJ-treated group, and a combined RJ + DOX treatment group. RJ was administered at 200 mg/kg/day by gavage, while DOX was given intraperitoneally at 80 mg/kg on days 10, 20, and 30. Tumor size, volume, and weight were monitored, and Kaplan-Meier analysis assessed survival. Biochemical and histopathological analyses showed that RJ modulated oxidative stress markers, reduced inflammation (IL-6, TNF-α, IL-8, interferon-γ), and inhibited tumor growth. RJ downregulated STAT3/FOXM1/ATG7 signaling pathways involved in tumor cell survival, proliferation, and metastasis. Additionally, RJ promoted mitochondrial apoptosis through increased p53 expression and reduced angiogenesis by suppressing VEGF. Immunohistochemistry revealed decreased Ki-67 expression, indicating reduced tumor cell proliferation. Molecular analyses confirmed RJ's role in modulating key apoptosis and angiogenesis pathways. When combined with DOX, RJ enhanced therapeutic efficacy, suggesting a synergistic effect. These findings highlight RJ's potential as a therapeutic agent targeting STAT3 and related pathways in NSCLC treatment, offering a promising complementary approach to conventional chemotherapy.

Cyclophosphamide (CYP)-induced cystitis is a significant clinical challenge in cancer patients, characterized by inflammation, oxidative stress, and muscle dysfunction. This study aimed to investigate the protective effects of lamotrigine cinnamaldehyde silver complex (LCSC) against CYP-induced cystitis. Sprague-Dawley rats were divided into six groups: Control, CYP-induced cystitis (Disease Control), mesna (standard drug), and three LCSC treatment groups (2.5, 5, and 10 mg/kg). Nociception, open-field test, bladder weight, edema, hemorrhage, vascular permeability, histopathological analysis, and the qRT-PCR expression of inflammatory and antioxidant genes were investigated. Molecular docking was performed using AutoDock Tools 1.5.6 software. LCSC treatment significantly reduced nociceptive responses and improved locomotor activity in a dose-dependent manner compared to the diseased control group. LCSC attenuated CYP-induced increases in bladder weight, edema, and hemorrhage. The higher doses of LCSC (5 and 10 mg/kg) were more effective in reducing vascular permeability. In vitro studies revealed that LCSC relaxed the urinary bladder strips in a concentration-dependent manner. LCSC also significantly upregulated the expression of antioxidant genes (catalase and superoxide dismutase) and downregulated inflammatory markers (inducible nitric oxide synthase, tumor necrosis factor-α, and transforming growth factor-β) in a dose-dependent manner. The histopathological evaluation confirmed the preservation of bladder architecture in LCSC-treated rats. LCSC demonstrated strong binding affinities and lower inhibition constants with key inflammatory and muscle protein receptors, including IL-1β, TNF-α, MLCP, and PKC, compared to Mesna. LCSC exhibited potent antioxidant, anti-inflammatory, and uroprotective effects in the CYP-induced rat model of cystitis as a potential therapeutic drug.

Bisphenol A has deleterious effects on reproductive, developmental, cell biological, and physiological functions. Here, we investigated the dosage effects of bisphenol A on the differentiation potential and apoptosis of mouse embryonic stem cells, and assessed some relevant regulatory mechanisms. Our results showed that bisphenol A at doses of 1-2 μmol/L triggers apoptotic processes without necrotic cell death in the ESC-B5 mouse embryonic stem cell line. No death effect was seen at treatment dosages of 0.5 μmol/L or less. Mechanistically, the application of 1-2 μmol/L bisphenol A directly increased the intracellular oxidative stress levels, significantly increased the cytoplasmic calcium and nitric oxide contents, decreased the mitochondrial membrane potential, activated caspases-9 and -3, and triggered programmed cell death. Interestingly, embryoid body formation assays showed that 0.5 μmol/L bisphenol A decreased the differentiation potential of ESC-B5 cells without inducing apoptotic processes. Together, our results indicate that treatment with 1-2 μmol/L bisphenol A induces apoptosis and triggers hazardous effects on the differentiation and developmental potential of mouse embryonic stem cells in vitro. These results provide important evidence that bisphenol A should be considered a potent cytotoxin that has dose-dependent impacts on differentiation and apoptosis in a mouse embryonic stem cell line.