This study evaluated the therapeutic efficacy of an ultrasound-assisted, NH 4 Cl-modified activated charcoal (MAC), prepared from Calligonum comosum wood, in a rat model of acute Paracetamol (APAP) intoxication. Previous in vitro studies under standard and simulated gastric and intestinal conditions confirmed MAC’s high adsorption capacity and stability, providing a rationale for its in vivo evaluation. Forty-nine male Wistar rats were allocated to seven groups: control, MAC alone, APAP alone, APAP followed by MAC at 5, 15, or 30 min, and APAP followed by hospital-grade activated charcoal (HAC) at 15 min. Serum APAP concentrations were measured at 4 and 24 h, while serum hepatic and renal biochemical markers, as well as blood-based oxidative stress biomarkers, were evaluated at 24 h. MAC reduced serum APAP concentrations across different post-exposure administration intervals. Compared with HAC, the MAC 15-min group demonstrated significantly greater APAP-lowering effects at both 4 and 24 h. In parallel, MAC attenuated APAP-induced elevations in ALT, AST, ALP, urea, creatinine, and MDA, and restored red blood cell GSH levels and erythrocyte SOD activity toward control values. These APAP-lowering and biochemical effects are likely associated with its improved physicochemical characteristics, including a well-developed porous structure, high specific surface area, and enriched oxygen- and nitrogen-containing functional groups, which together promote superior adsorption capacity. Overall, these findings support further preclinical investigation of MAC as a gastrointestinal adsorbent for acute APAP intoxication.
Background Paracetamol overdose is a leading cause of acute liver failure worldwide, necessitating alternative therapeutic agents. Cytidine 5′-diphosphocholine (CDP-choline, CDPC) exerts neuroprotective effects and may offer hepatoprotection via membrane-stabilizing, anti-inflammatory, and anti-apoptotic actions. Objectives This study aimed to evaluate the structural hepatoprotective potential of CDPC in a rat model of acute paracetamol toxicity. Design Randomized, controlled experimental animal study. Methods Twenty-four male Wistar albino rats were randomized into four groups ( n = 6 /group): vehicle control, toxicity control (paracetamol 4 g/kg followed by saline at 6 h), and two CDPC treatment groups (250 and 500 mg/kg CDPC administered 6 h after paracetamol). Liver tissues were harvested 48 h post-dosing for histopathological scoring of hepatocyte degeneration, sinusoidal congestion, centrilobular necrosis, and parenchymal hemorrhage. Results High-dose CDPC (500 mg/kg) significantly reduced the incidence and severity of hepatocyte degeneration and sinusoidal congestion ( p < 0.001 ). Severe lesions were absent in the 500 mg/kg group. Centrilobular necrosis and parenchymal hemorrhage showed a non-significant decreasing trend with CDPC treatment. Conclusion CDPC, particularly at 500 mg/kg, exhibits protective potential against paracetamol-induced structural liver injury. Further independent preclinical studies with biochemical and mechanistic endpoints are required to characterize its therapeutic efficacy. Registration Not applicable.
Background Chronic arsenic exposure is closely associated with cognitive dysfunction and central nervous system injury. This study aimed to investigate the neuroprotective effects of gastrodin and elucidate its underlying mechanisms in a mouse model of chronic arsenic-induced neurotoxicity. Methods A chronic arsenic intoxication model was established in mice through arsenic-containing drinking water, followed by oral gavage administration of Gas (100 mg/kg). Behavioral tests were conducted to evaluate locomotor activity and hippocampus-dependent spatial learning and memory. Network pharmacology and molecular docking analyses were integrated to predict potential therapeutic targets and pathways. Candidate targets were subsequently validated by Western blotting, biochemical assays, and immunohistochemical analyses. Results Gas significantly alleviated arsenic-induced deficits in exploratory behavior and spatial memory. Integrated network pharmacology and molecular docking analyses identified glycogen synthase kinase-3β (GSK3β) as a key hub target with favorable binding affinity for Gas. In vivo validation demonstrated that chronic arsenic exposure increased total GSK3β and p-NF-κB p65 expression, reduced inhibitory phosphorylation of GSK3β at Ser9, and induced pronounced oxidative stress, as evidenced by elevated malondialdehyde (MDA) levels and a compensatory increase in superoxide dismutase (SOD) activity. Gas administration markedly reversed these alterations, restoring redox homeostasis and suppressing GSK3β/NF-κB signaling activation. Conclusions Gastrodin exerts neuroprotective effects against chronic arsenic-induced neurotoxicity, associated with the modulation of GSK3β/NF-κB signaling and alleviation of oxidative stress. These findings suggest that GSK3β acts as a putative mediator of gastrodin’s therapeutic actions.
Objective To systematically evaluate nephrotoxicity associated with glyphosate (GLY) and glyphosate-based herbicides (GBHs) in mammalian experimental models and quantify the effects on renal function and oxidative stress. Methods PubMed, Embase, Web of Science, and Scopus were searched for eligible animal studies through April 2026. Risk of bias was assessed using SYRCLE’s tool. Standardized mean differences ( SMDs ) with 95% confidence intervals (CIs) were calculated, and fixed- or random-effects models were selected according to heterogeneity criteria. Exploratory subgroup analyses by dose, exposure duration, and formulation, together with sensitivity analyses, explored potential sources of heterogeneity. Results Thirty-four studies were included. Exposure to GLY and GBHs was associated with increased serum creatinine ( SMD = 1.31) and urea ( SMD = 1.26), decreased SOD ( SMD = −1.75), CAT ( SMD = −1.48), and GSH ( SMD = −2.51), and increased MDA ( SMD = 2.02), whereas GPx was not significantly affected ( SMD = −0.75). Substantial heterogeneity was observed across most outcomes ( I 2 = 74.7%−81.6%). Subgroup analyses indicated variations in effect estimates according to dose and exposure duration for urea, SOD, and GSH, although no consistent dose- or duration-related pattern was evident. Sensitivity analyses supported robustness of the pooled estimates, while small-study effects were detected for several biomarkers. Conclusion Exposure to GLY and GBHs is associated with impaired renal function and oxidative imbalance in mammalian experimental models. Despite substantial heterogeneity, the evidence supports the biological plausibility of GLY- and GBH-associated nephrotoxicity. Further standardized, long-term studies are needed to clarify exposure–response relationships and improve translation to human health risk assessment.
Introduction The immunoproteasome is integral to endothelial redox homeostasis and protein quality control; however, its modulation by cigarette smoke remains unclear. We investigated whether cigarette smoke extract (CSE) suppresses immunoproteasome expression and promotes oxidative and inflammatory activation in vascular endothelial cells (VECs). Methods Mouse VECs were exposed to 1.0% CSE for 16 h or treated with the β5i-selective inhibitor ONX-0914 (0.5–1.0 μM, 24–36 h). mRNA expression levels of proteasome subunits, NADPH oxidase 4 (NOX4), and inflammatory mediators were assessed by quantitative PCR. Proteasomal activity and intracellular reactive oxygen species (ROS) were quantified using luminescent assays. β5i expression in small pulmonary arterioles (≤0.5 mm) from smokers (n = 10) and nonsmokers (n = 10) was analyzed by immunohistochemistry. Results CSE significantly suppressed immunoproteasome expression, reducing β5i mRNA by 66% ± 4% ( p = 0.0037) and decreasing proteasomal activity. Treatment with ONX-0914 increased intracellular ROS and upregulated NOX4 and inflammatory mediators, including monocyte chemoattractant protein-1 (approximately 6- to 7-fold at 0.5 μM for 36 h). Reduced endothelial β5i expression was more frequent in smokers than in nonsmokers. Discussion Cigarette smoke-associated β5i suppression is linked to endothelial oxidative stress and inflammation, suggesting a potential mechanism underlying smoking-related vascular dysfunction.
