Journal of Applied Toxicology最新文献

Microplastics (MPs), diameter < 5 mm, are becoming a major environmental health concern issue but there is still less information available about the exposure and toxicity of MPs on mammal health. In the current study, we assessed the effects of MPs, Polyvinyl chloride (PVC), and Polystyrene (PS) toxicity on body weight, blood glucose, different blood parameters, and oxidative stress of Wistar albino rats. SEM analysis was performed for the characterization of PVC and PS MPs. In in vivo analysis, the rats were divided into five groups and four groups; Groups 2 to 5 were exposed to PVC and PS at different doses (300 and 1000 mg/kg), and Group 1 was used as a control group. After 8 weeks of exposure, the change in body weight and blood parameters was determined, which showed a significant alteration in the animals' bodies. The addition of polyvinyl chloride and polystyrene to the rats showed a significant decline in body weight (PVC 0.0021: PS 0.0055) and an increase in blood glucose (PVC 0.0006; PS 0.0009). The harmful effect was also analyzed on internal organs which depicted the increase in total cholesterol (PVC 0.0006; PS 0.0009), triglyceride (PVC 0.0001; PS 0.0026), low-density lipoprotein (PVC 0.0226; PS 0.0051), alanine transaminase (PVC; PS < 0.0001), albumin (PVC 0.0037; PS 0.0001), creatinine (PVC; PS < 0.0001), uric acid (PVC 0.0009; PS 0.0014), superoxide dismutase (PVC 0.0025; PS 0.0017), malonaldehyde (PVC; PS < 0.0001) whereas decrease in high density lipoprotein (PVC 0.0255; PS 0.0057), alkaline phosphatase (PVC; PS < 0.0001) and catalase (PVC 0.0095; PS 0.030). Also, the histopathological analysis of the renal and hepatic tissue showed the toxicological effect of PVC and PS. The outcomes of the current work depicted that the MPs, PVC, and PS have toxic effects on animals and humans.

Chlorfenapyr (CFP) is an insecticide known to induce hepatotoxicity through oxidative stress, inflammation, and mitochondrial dysfunction. Resveratrol (RES) exhibits antioxidant and anti-inflammatory properties, and its delivery via chitosan nanoparticles (RES-CNPs) may enhance its protective effects. This study aimed to investigate the hepatoprotective potential of RES and RES-CNPs against CFP-induced liver damage in Wistar rats. Sixty male Wistar rats were randomly divided into six groups (n = 10): control, RES, RES-CNPs, CFP, CFP + RES, and CFP + RES-CNPs. Treatments were administered orally for 30 days. Liver function, lipid profile, oxidative stress markers, antioxidant defense system, energy metabolism, mitochondrial function, inflammatory gene expression, histopathology, and ultrastructure were evaluated exposure significantly decreased total protein, albumin, antioxidant levels (GSH, CAT, SOD, GPX), ATP, and PDH activity, while increasing liver enzymes (AST, ALT, ALP), lipid peroxidation (MDA, PCO), mitochondrial dysfunction, inflammatory gene expression (NF-κB, TNF-α, IL-6), CRP, and total leukocyte count (p < 0.05). Co-administration of RES-CNPs significantly restored these biochemical, molecular, and histological parameters, showing superior efficacy to crude RES in most endpoints and achieving values close to the negative control for several markers (p > 0.05). Histopathological and ultrastructural analyses confirmed CFP-induced hepatocyte degeneration and necrosis, which were ameliorated by RES-CNPs, with near-normal liver architecture and cellular integrity. RES-CNPs effectively mitigate CFP-induced hepatotoxicity by restoring liver function, enhancing antioxidant defenses, preserving mitochondrial function, and suppressing inflammation. RES-CNPs demonstrated superior hepatoprotective effects compared to crude RES, highlighting their potential as a therapeutic strategy against xenobiotic-induced liver injury.

The transport of pharmaceutical compounds into aquatic ecosystems poses a significant environmental threat, particularly due to the presence of drugs that cannot be completely removed during wastewater treatment processes. Diclofenac (DCF), one of the most widely used nonsteroidal anti-inflammatory drugs worldwide, is among the pharmaceuticals frequently detected in aquatic environments due to its high consumption levels and persistence in the environment. It is known that this compound causes neurotoxicity, behavioral disorders, and physiological stress responses in aquatic organisms even at low concentrations. This study aimed to determine the effects of diclofenac exposure on oxidative stress, circadian rhythm, and behavioral parameters in zebrafish larvae. For this purpose, zebrafish embryos and early-stage larvae were exposed to DCF at concentrations of 0.5, 2.5, and 12.5 μg/L for 120 h. Subsequently, to investigate the effect of DCF on oxidative stress, SOD, CAT, GPX, and AChE enzyme activities and gene expression levels were analyzed. To examine its effects on behavior and circadian rhythm, thigmotaxis and locomotor activity analyses were performed. Additionally, to determine the molecular-level effects of behavioral changes, the expression levels of the bdnf, 5ht4, crhr, bmal1, per, and gnat2 genes were analyzed. Overall, our findings indicate that DCF affects behavioral activity, neurotransmitter metabolism, oxidative stress response, circadian rhythm, and retina-related molecular regulators in zebrafish larvae in a multilevel manner. These results highlight the potential risks of pharmaceutical contaminants on neurodevelopmental processes in aquatic ecosystems and demonstrate that even environmental doses can produce complex responses in biological systems.

Poisoning in children is a significant public health concern globally. It represents an important cause of morbidity and mortality in children and adolescents. This study was designed to document types of ingested poisons, the presentation, and outcomes of childhood poisoning at two tertiary hospitals in Harare, Zimbabwe. A hospital-based descriptive cross-sectional study was conducted from March 2019 to June 2020. Data on socio-demographic status, types of poison, clinical assessment, and outcome were collected through an interviewer-administered questionnaire and patients' records. A total of 177 children were admitted with poisoning during the study period, of whom 59.3% were male. The majority (75.1%) were below 6 years of age. Pesticide poisoning was the most common exposure (31.1%). Most of the poisoning cases were accidental (84.7%) and oral ingestion was the primary route (97.7%). According to the poison severity score (PSS), 63.2% of cases were minor and 3.4% were severe. Gastrointestinal symptoms were the most frequent presentation. Two children (1.1%) were admitted into the ICU, 170 (96%) fully recovered, 2 (1.1%) were discharged with sequalae, and 3 (1.7%) died. The three children who died had taken pesticides: one unknown pesticide, aluminum phosphide, and organophosphate (diazinon), and the case fatality rate for the study was 1.7%. Acute poisoning is a significant preventable cause of morbidity in children. Pesticides were the most common cause of poisoning and mortality. The majority of the poisoning was unintentional and occurred mostly in male children below 6 years of age.

Type 2 diabetes mellitus (T2DM), the predominant form of diabetes mellitus (DM), has been established as a key etiological factor in male infertility. The incidence of T2DM among reproductive-aged males has shown a progressive annual increase, potentially contributing to the observed decline in fertility rates. As a primary oral hypoglycemic medication in the management of T2DM, metformin requires comprehensive investigation into its impacts on male reproductive function. The effects of metformin, at concentrations within the therapeutic range, on the functional competence of capacitated human sperm were assessed in vitro to elucidate the involved mechanisms. Following exposure in capacitation medium, sperm functions critical for fertilization, such as motility, penetration ability, capacitation, acrosome reaction, and hyperactivation were systematically evaluated. The potential mechanisms such as 5'-AMP-activated protein kinase phosphorylation and tyrosine phosphorylation of sperm in capacitated state were also measured by western blot. The results indicate that metformin, at 40 and 80 μM, markedly reduced the enhancement of sperm parameters induced by HTF++ buffer. This detrimental effect is attributable to the inhibition of both AMP-activated protein kinase (AMPK) activation and tyrosine phosphorylation signaling pathways. Our findings indicate that as a commonly used medicine for T2DM in clinic, the potential negative impact of metformin on fertility should be considered, especially for men of reproductive age who are undergoing glucose management and diabetes treatment.

Silver nanoparticles (Ag-NPs) are being increasingly integrated into biomedical and consumer products; however, their long-term safety is not fully understood. The liver and kidneys demonstrate an apparent susceptibility to the accumulation of Ag-NPs; however, the intensity and reversibility of the consequent toxicity necessitate further investigation. This study aimed to outline the hepatorenal toxic effects of orally administered Ag-NPs and to assess the potential for recovery through longitudinal biochemical, histopathological, and apoptotic assessments. Adult male albino rats were divided into control, Ag-NPs-treated, and recovery groups. Animals were administered oral Ag-NPs at a dosage of 1 mg/kg/day for a duration of 28 days. Biochemical assays of liver enzymes, renal function, and oxidative stress markers were assessed. Histopathological examination and immunohistochemical analysis for Bcl-2 and Bax expression were evaluated. Assessments were conducted immediately after treatment and at 2- and 8-week recovery intervals. Subchronic administration of Ag-NPs led to significant hepatorenal injury, as evidenced by elevated serum levels of ALT, AST, urea, and creatinine, increased malondialdehyde, and reduced antioxidant defenses. Histological analysis revealed hepatocellular degeneration, necrosis, vascular congestion, and renal tubular damage. Immunohistochemistry demonstrated a proapoptotic shift characterized by the downregulation of Bcl-2 and the upregulation of Bax. Longitudinal monitoring revealed significant recovery, with partial resolution of biochemical and structural changes at 2 weeks and near-complete restoration of hepatic function and morphology by 8 weeks. In contrast, renal recovery was relatively delayed. The oral administration of Ag-NPs results in significant, nevertheless predominantly reversible, hepatorenal toxicity, which is mediated through oxidative stress and apoptosis. Longitudinal monitoring has become essential for tracking the evolving patterns of injury and recovery, demonstrating its significance in nanoparticle toxicology and risk assessment. A key innovation of this study is the longitudinal recovery design, which allowed for dynamic evaluation of the progression and reversibility of hepatorenal injury following the cessation of Ag-NPs exposure.

Toxicological assessment is essential in NP approval for health and medical applications. Although 2D cell culture has been widely used, 3D models, especially spheroids, provide better predictive value for toxicological risk assessments since they replicate complex cellular interactions more accurately. In this study, different cytotoxicity assays were used to conduct a comparative nanotoxicological analysis of Adipose Stem Cells (ASC) grown in 2D and 3D (spheroid) systems, based on OECD guidelines. To evaluate the toxicity of nanostructured carbonated hydroxyapatite (nCHA) in ASC spheroids, the Neutral Red Uptake assay, and an ATP quantification assay were used. The results obtained from 2D cell monolayers and 3D spheroids were compared to determine the most suitable assay for spheroid analysis. Moreover, the IC50 for SDS treatment was determined and the spheroid morphology was analyzed after treatment with the nanoparticles. Overall, the three assays confirmed the absence of cytotoxicity of nCHA NPs in the ASC monolayer. In addition, the ATP quantification assay confirmed the absence of cytotoxicity of nCHA NPs in the ASC spheroids. Curiously, SDS cytotoxicity was higher in spheroids than in monolayer cultures, inducing the disaggregation of spheroids in a facile and concentration-dependent manner (IC₅₀ = 9.67 μg/mL in spheroids, approximately eight times lower than the IC₅₀ observed in monolayer cultures, 76 μg/mL). The nCHA NPs were also explored as spheroid functionalization agents. The nanoparticles did not affect ASC spheroids' morphology and diameter, and the nCHA are located mainly in the extracellular matrix of spheroids mimicking the mineral component of bone. Collectively, our findings demonstrated that spheroids are more sensitive than monolayers for evaluating nanoparticle biocompatibility, highlighting the potential of 3D cultures as new advanced models (NAMs) for improved nanotoxicology assessments. Furthermore, the functionalization of ASC spheroids with nCHA NP holds potential both as a 3D osteogenesis model and as a therapeutic product to promote bone regeneration.

This study investigates the effects of occupational carbon dioxide (CO₂) exposure on corneal tissue through Fourier transform infrared (FTIR) spectroscopy and chemometric analysis. Human activities have significantly increased atmospheric CO₂ levels, leading to potential health risks, particularly in confined environments such as mining, submarines, and enclosed workspaces. While CO₂ exposure is commonly associated with respiratory and cardiovascular effects, its impact on ocular health remains underexplored. Rats were exposed to three different CO₂ concentrations (3%, 5%, and 10%) in a controlled chamber for 8 h per day over a 30-day period. Second derivative analysis of corneal FTIR spectra revealed significant alterations in protein secondary structures, lipid composition, and phosphate group alterations, indicating CO₂-induced biochemical changes. Notably, exposure led to a shift in the amide I band from 1650 to 1643 cm^-1, suggesting a transition from α-helix to random coil structures in corneal proteins, which compromises tissue integrity. Changes in lipid hydrocarbon chain vibrations and increased gauche rotamers indicated disruptions in membrane order and fluidity. Additionally, phospholipid and nucleic acid modifications were observed, potentially affecting cellular stability. The study provides valuable insights into corneal bio-molecular alterations due to CO₂ exposure, contributing to a deeper understanding of environmental and occupational eye health risks.

Fentanyl, an ultra-potent synthetic opioid, has traditionally been characterized by its acute toxic effects, particularly respiratory depression. However, accumulating research indicates that its neurobiological influence extends far beyond its short pharmacological window, intersecting with several core mechanisms implicated in major neurodegenerative disorders. This review integrates multiscale evidence to propose a unified conceptual framework in which fentanyl may function not only as an acute neurotoxin but also as a putative accelerator of long-term neurodegenerative vulnerability. Drawing from molecular signaling, cellular stress pathways, glial-neuronal cross-talk, neurovascular regulation, synaptic architecture, and large-scale neural networks, we highlight fentanyl's capacity to trigger a convergent cascade encompassing hypoxic-metabolic reprogramming, mitochondrial fragmentation, TLR4-NF-κB-driven inflammation, NLRP3 inflammasome activation, complement-mediated synaptic pruning, astrocytic EAAT2 downregulation, and blood-brain barrier compromise. These alterations propagate through recursive cross-talk loops that progressively diminish neuronal resilience, destabilize oscillatory coherence, and weaken circuit-level adaptability. Importantly, mechanistic overlaps with Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis suggest that fentanyl exposure may be mechanistically associated with processes capable of accelerating disease onset, exacerbating progression, or unmasking latent vulnerabilities, particularly in genetically or metabolically predisposed individuals. By reframing fentanyl as a systems-level destabilizer capable of imprinting persistent neurobiological changes, this model underscores the need for comprehensive biomarker development, longitudinal risk assessment, and targeted neuroprotective interventions. The integrative framework presented herein offers a foundation for predicting the long-term neurological consequences of fentanyl exposure and calls for urgent reconsideration of its role in population-level neurodegenerative risk.