Frontiers in toxicology最新文献

Introduction: This study investigated the effects of cadmium (Cd) and β-cypermethrin (β-CP), both singly and in combination, on oxidative stress responses and tissue morphology in zebrafish.

Methods: Through acute exposure experiments, we evaluated the acute toxicity and behavioral responses of zebrafish to these two compounds.

Results: The LC50 values of contaminants for zebrafish at 24 h, 48 h, 72 h, and 96 h were 25.36, 22.94, 20.36, and 17.83 mg/L for Cd, and 6.41, 4.96, 4.23, and 3.75 μg/L for β-CP, respectively. The results showed that β- CP exhibited higher acute toxicity compared to Cd, with pronounced toxic reactions including body curling, convulsions, accelerated operculum flapping, and significantly reduced swimming ability. In contrast, cadmium (Cd) elicited milder acute toxicity symptoms yet significantly disrupted key oxidative stress parameters, including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). During the chronic co-exposure phase, the combined treatment of Cd and β-cypermethrin (β-CP) resulted in more severe toxicity than individual exposures, as supported by marked bioaccumulation of both contaminants and extensive histopathological impairments-such as neuronal degeneration in the brain, hepatocyte necrosis in the liver, and villus atrophy in the intestine. Quantitative assessments further indicated that the co-exposure provoked the strongest oxidative stress response, with the highest increases observed during the acute phase-reaching up to 75% for SOD, 51% for CAT, and 52% for MDA relative to the control group (P < 0.05).

Discussion: This study revealed the severe toxic effects of combined exposure to Cd and β-CP on zebrafish, underscoring the need for increased attention to the potential ecological risks of heavy metal and pesticide pollution in aquatic environments.

Background: Lithium remains a first-line treatment for bipolar disorder, though its narrow therapeutic window poses a significant risk of toxicity. Severe intoxication can lead to neurologic, renal, gastrointestinal, and endocrine complications. Extracorporeal therapies are the mainstay in managing life-threatening cases, particularly when serum concentration exceed 4.0 mmol/L or when renal function is impaired. Intermittent hemodialysis (HD) is the recommended extracorporeal treatment due to lithium's low molecular weight and minimal protein binding. Expanded hemodialysis (HDx) with medium cut-off (MCO) membranes, designed to enhance solute clearance, may represent a promising alternative.

Case report: We present a case of acute lithium intoxication in a 48-year-old male with a history of recurrent suicidal behavior and chronic lithium therapy. The patient arrived at the emergency department in a deep coma (GCS 3), with a serum lithium concentration of 4.5 mmol/L and preserved renal function. He underwent two intermittent HDx sessions using a Theranova® TH-400 MCO membrane. Serum lithium concentration declined to 1.6 mmol/L after the first session and progressively to 0.1 mmol/L within 72 h. No treatment-related complications were observed.

Conclusion: This case described the potential utility of HDx with the MCO membrane (Theranova® 400) in managing severe lithium poisoning, achieving effective and sustained drug clearance. While HDx-MCO may offer a viable alternative to conventional HD, especially in settings where enhanced solute removal is desirable, further studies are needed to determine its efficacy and clinical role in lithium toxicity management.

Background: Folk medicine has long employed plants to treat diseases. Consumers believe herbal treatments are safe since they are natural. Studies suggest that some plant compounds can cause chromosomal damage at high concentrations, while some can mitigate the genotoxicity caused by toxic substances. Sonchus oleraceus L. is a popular medicinal herb in Saudi Arabia as well as in the rest of the world. It has antioxidant, anticancer, and other biological properties. Sodium benzoate (SB) is a versatile food preservative used in packaged food and drink industries; it has been found to cause genotoxicity and DNA damage. Therefore, it is necessary to investigate the biological activity of Sonchus oleraceus extract and its ability to mitigate Sodium Benzoate-induced cytotoxicity and genotoxicity.

Aim: The current study evaluates biological properties of S. oleraceus leaf extract and reveals its potential mitigating role against sodium benzoate by using the Allium cepa in vivo bioassay and molecular analysis.

Methodology: S. oleraceus aqueous extract and sodium benzoate was prepared. Then, the effective concentration (EC₅₀) was determined, and concentrations with control were selected for each group. Roots of A. cepa were treated for 24, 48, and 72 h with concentrations (21.5, 43, and 64.5 mg/mL) of extracts with or without combined treatment with 4 mg/mL of SB for 24 h. The cytotoxicity was investigated by using mitotic index (MI) and the genotoxicity by micronuclei (MN), chromosomal abnormalities (CA) and then using the ISSR-PCR markers for molecular analysis.

Results: Compared to the controls, S. oleraceus and SB application as a single treatment decreased root length and MI index, and CA were increased, especially in higher concentrations. DNA damage was reported by ISSR-PCR markers. However, SB toxicity was mitigated by the co-treatment of S. oleraceus extract, which showed partial improvement in all variables depending on the application concentration, possibly due to its antioxidant properties. The cytogenetic assay showed the best antimutagenic efficacy at 21.5 mg/mL with a moderate inhibition rate greater than 25%.

Conclusion: The results indicate that the aqueous extract of S. oleraceus leaves, as a single treatment, induces a genotoxic effect on A. cepa cells, especially at high concentrations, and that S. oleraceus leaf extract, as a co-treatment, acts as a mutagen at high concentrations and a moderate antimutagenic at low concentrations. The findings also indicate that the cytotoxic capacity of SB in A. cepa highlights potential concerns that warrant further investigation.

Green microalgae, particularly Chlorella vulgaris, are a rich source of bioactive and nutritional compounds, making them promising candidates for nutraceutical applications. This study evaluated the antioxidant capacity, phenolic composition, and potential health effects of Chlorella vulgaris supplementation (1% and 8%) in male BALB/c mice over 4 weeks, as well as its preventive role in a murine model of chronic obstructive pulmonary disease (COPD). The extract showed a high antioxidant potential, supported by its phenolic and carotenoid profile. Supplementation, especially at 8%, enhanced antioxidant defences without signs of liver or kidney toxicity. In the COPD model, C. vulgaris reduced inflammation, improved oxidative stress balance, and partially restored normal lung structure. Additionally, changes in caecal metabolites suggested a positive impact on gut microbiota and metabolic homeostasis. Overall, C. vulgaris supplementation demonstrated detoxifying, antioxidant, and anti-inflammatory benefits, supporting its potential use as a functional food, particularly under stress-related conditions such as COPD.

Background and objectives: Scorpion envenomation presents with a wide spectrum of clinical manifestations, ranging from mild local symptoms to severe systemic complications. This study aimed to evaluate the diagnostic and prognostic utility of GPX4, IL-13, periostin, SDF-4, and thiol/disulfide homeostasis parameters in adult patients with confirmed scorpion envenomation.

Materials and methods: This prospective observational study included 60 adult patients with confirmed scorpion stings and 33 healthy controls. Serum levels of GPX4, IL-13, periostin, and SDF-4 were measured using ELISA. Thiol/disulfide balance was evaluated by spectrophotometric assay. Clinical severity was graded using a four-level scale (Grade I-IV) based on local and systemic findings. Receiver operating characteristic (ROC) analysis and logistic regression were performed to assess the diagnostic performance and independent predictive value of biomarkers.

Results: Patients exhibited significantly lower GPX4, native thiol, and total thiol levels, and higher disulfide, IL-13, periostin, and SDF-4 levels compared to controls (p < 0.001). The disulfide/native thiol and disulfide/total thiol ratios were also elevated. GPX4 (AUC = 0.984), SDF-4 (AUC = 0.900), and periostin (AUC = 0.850) demonstrated excellent diagnostic accuracy. GPX4 and disulfide levels were identified as independent predictors of envenomation. Biomarker levels significantly correlated with clinical severity grades.

Conclusion: Oxidative and inflammatory biomarkers, particularly GPX4, disulfide/native thiol ratio, IL-13, and periostin, provide diagnostic and prognostic value in scorpion envenomation. Incorporating these parameters into clinical assessment may enhance early risk stratification and guide management in the emergency setting.

Background: Exposure to the herbicide glyphosate may contribute to anxiety-related disorders. The mechanisms by which this occurs may involve effects on brain regions or alterations of gut microbiota implicated in emotions. Pre-clinical studies use unusually high doses to which humans may not normally be exposed. The effects of glyphosate on anxiety at doses considered safe are largely unexplored.

Methods: Adult male rats were administered glyphosate at a dose considered safe for 16 weeks. After 4 and 10 weeks, anxiety-like behaviors were tested in the open field and elevated plus maze, respectively. After 14 weeks, rats interacted with a novel neutral object, followed by a naïve rat of the same age and sex as a conspecific. Lastly, after 16 weeks, rats underwent fear conditioning, and freezing was quantified. Upon completion of the experiments, cellular activity was assessed using immunohistochemistry in brain regions implicated in anxiety and fear. Fecal pellets were collected to extract DNA and perform 16S rRNA community analyses.

Results: Glyphosate increases anxiety in the elevated plus maze after 10 weeks. Moreover, glyphosate decreases interaction to a novel object, but not to the conspecific, after 14 weeks. Furthermore, freezing increases to a novel neutral tone, but not a conditioned tone, after 16 weeks. Behavioral changes correspond to increases in cellular activity in the bed nucleus of the stria terminalis. Furthermore, we observed that glyphosate induces changes in the gut microbiota leading to a decrease in Lactobacillus species.

Conclusion: Glyphosate increases threat interpretation and alters cellular activity in brain regions implicated in promoting anxiety. Also, glyphosate induces gut dysbiosis and reduces the abundance of Lactobacillus, bacteria that play a role in the production of serotonin, which may further exacerbate the anxiogenic effect of glyphosate.

Introduction: The presence of central nervous system (CNS) safety concerns during early clinical testing that were not picked up in standard preclinical assessment is a major cause of attrition in drug development. It is also very expensive, time consuming and potentially dangerous for clinical trial participants. Rodent home cage monitoring approaches have previously been shown to deliver significant animal welfare benefits through group/social housing, minimal interventions avoiding stress that can confound results, and in some cases also animal reduction benefits with the multiplex data acquisition requiring fewer total animals. Here we looked at the utility of home cage monitoring to uncover potential CNS effects not identified using standard safety pharmacology tests.

Method: We hypothesised that longitudinal behavioural assessment-by capturing non-evoked behaviour and reducing sampling artefacts-would be more sensitive to adverse reactions in preclinical animal models (i.e., rodents). To test this, we selected three compounds which previously passed standard safety tests but were failed later including two during clinical trials. We validated the general methodology for using home cage monitoring in safety assessment study designs from single doses to repeat dosing for up to 4 weeks. We then re-tested the three compounds in single dose studies.

Results/discussion: We showed that the methodology fits well with standard study designs. More importantly we uncovered significant findings in all three compounds that were not observed in the original classic safety pharmacology tests. The lack of such effects observed in standard preclinical assessment likely reflects functional differences between the limited observational snapshots characteristic of this approach and the more comprehensive temporal resolution enabled by continuous home cage monitoring.

Introduction: This study evaluates the ecotoxicity of micro- and nano-sized titanium dioxide (TiO₂), either as active ingredients or incorporated into sunscreen formulations in the aquatic environment, by proposing a leaching protocol simulating a realistic scenario of human immersion in freshwater and seawater.

Methods: To this aim, an ecotoxicological screening of micro- and nano-TiO₂ active ingredients and incorporated into sunscreens was applied, by evaluating acute and sub-acute responses (bioluminescence and growth inhibition, immobilization, behaviour) in freshwater and marine bacteria, microalgae and crustaceans. Then, Ti concentration was measured in the leachates of sunscreens through Inductively Coupled Plasma mass spectrometry (ICP-MS).

Results and discussion: Toxic effects (EC₅₀s) were only found in microalgae and crustaceans exposed to TiO₂ active ingredients. No toxicity occurred with sunscreens formulations, although significant algal growth inhibition was determined, likely due to TiO₂ size rather than Ti concentration. By integrating a sunscreen leachate based methodology with a multi-species and multi-endpoint approach, this study introduces a novel ecosafety-oriented assessment of TiO₂ providing realistic ecotoxicological evidence relevant to freshwater and marine environments.