Toxicology Research最新文献

Background: Poisoning-induced shock is a serious medical emergency with a high mortality rate. Hospitalized poisoned individuals experience multiple adverse cardiovascular events that could progress to cardiac arrest. This study was designed to compare the prognostic role of the admission shock index and plasma copeptin level in shocked poisoned patients and to evaluate their associations with initial patients' characteristics and outcomes.

Methods: We conducted a prospective study on acutely poisoned adult patients.

Results: A total of 41 patients were enrolled in the study. The mean age of all patients was 27.05 ± 10.99 years and most of the patients were females (n = 27, 66%). Pesticides were the most common type of poisoning (n = 18, 44%), followed by cardiovascular drugs (n = 12, 29.3%). Eleven (26.8%) patients died during the hospital stay length. The initial serum copeptin level and shock index could predict organ dysfunction indexed by sequential organ assessment score (SOFA) with area under the curve (AUCs) of 0.862 and 0.755, respectively. Initial serum copeptin and lactate levels, SOFA score, and their combination can strongly differentiate between survivors and non-survivors with an AUC of 0.944, 0.885, and 0.959, and 0.994, respectively.

Conclusion: We concluded that the shock index, serum lactate level, and SOFA score may help in risk stratifying patients and predicting outcomes in critically ill patients with poisoning-induced shock. Copeptin is superior to the shock index in predicting mortality among the studied patients. However, a combination of SOFA score, serum copeptin level, and serum lactate level can develop a more predominant prediction for overall clinical outcomes in these patients.

Objective: Storke is a leading cause of death and disability affecting million people worldwide, 80% of which is ischemic stroke (IS). Recently, traditional Chinese medicines (TCMs) have received great attentions in treating IS due to their low poisonous effects and high safety. Buyang Huanwu Decoction (BHD), a famous and classical Chinese prescription, has been used for treating stroke-induced disability for centuries. Yet, its underlying mechanism is still in fancy.

Methods: We first constructed an IS model by middle cerebral artery occlusion (MCAO). Then, a metabonomics study on serum samples was performed using UHPLC-QTOF/MS, followed by multivariate data analysis including principal components analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA).

Results: Metabolic profiling of PCA indicated metabolic perturbation caused by MCAO was regulated by BHD back to normal levels, which is in agreement with the neurobehavioral evaluations. In the OPLS-DA, 12 metabolites were screened as potential biomarkers involved in MCAO-induced IS. Three metabolic pathways were recognized as the most relevant pathways, involving one carbon pool by folate, sphingolipid metabolism and inositol phosphate metabolism. BHD significantly reversed the abnormality of 7 metabolites to normal levels.

Conclusions: This is the first study to investigate the effect of BHD on IS at the metabolite level and to reveal the underlying mechanisms of BHD, which is complementary to neurobehavioral evaluation. In a broad sense, the current study brings novel and valuable insights to evaluate efficacy of TCMs, to interpret the action mechanisms, and to provide the theoretical basis for further research on the therapeutic mechanisms in clinical practice.

Background: Ehrlich ascites carcinoma (EAC) is a rapidly growing and undifferentiated tumor that can prompt oxidative stress and liver toxicity, whereas chitosan and Grifola Frondosa have widely recognized biological qualities. Therefore, our study designed to assess the potential ameliorative ability of chitosan nanoparticles (CS NPs) and Grifola Frondosa nanoparticles (GF-loaded casein NPs) on EAC-induced hepatic injury in mice.

Methods: A total of 60 female albino mice were segregated into 6 groups (10 mice each), G1, control group; G2, CS NPs group; G3, GF-loaded casein NPs group; G4, EAC group; G5, EAC treated with CS NPs; G6, EAC treated with GF-loaded casein NPs.

Results: According to the findings, EAC considerably increased serum activities of ALT, AST, ALP as well as LDL, cholesterol, and triglycerides levels coincided with marked decrease in albumin and total protein content in liver tissue. At the same time, it drastically lowered GSH levels and catalase activity while significantly elevating MDA levels. In addition, EAC caused DNA damage and apoptosis by decreasing Bcl-2 while increasing p53 expressions. However, either CS NPs or GF-loaded casein NPs therapy improved liver architecture and functioning, increased antioxidant parameters, and prevented hepatocyte death in EAC mice.

Conclusions: Our findings concluded that CS NPs and GF-loaded casein NPs have insulating functions against EAC-induced hepatic damage in mice.

Introduction: Metal oxide nanoparticles are currently used widely in many aspects of human and animal life with broad prospects for biomedical purposes. The present work was carried out to investigate the effects of orally administrated TiO2NPs, ZnONPs, IONs and Al₂O₃NPs on the mRNA expression level of CYP 1A1 and NBN in the rat liver.

Materials and methods: Four groups of male Albino rats were given their respective treatment orally for 60 days in a dose of 1/20 of the LD50 TiO2NPs (600 mg/Kg b.wt/day), ZnONPs (340 mg/Kg b.wt/day), IONs (200 mg/kg b.wt/day) and Al₂O₃NPs (100 mg/Kg b.wt/day) and a fifth group served as a control group.

Rresults: The mRNA level of CYP 1A1 and NBN showed up-regulation in all the NPs-treated groups relative to the control group. ZnONPs group recorded the highest expression level while the TiO2NPs group showed the lowest expression level transcript. Conclusion:The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide, iron oxide nanoparticles and titanium dioxide, respectively.

Acute anticholinesterase pesticide poisoning is a serious clinical problem, particularly in developing countries. Atropine is the most acceptable treatment for acute anticholinesterase poisoning. However, it only stops fluid production. Albuterol is a beta-2 receptor agonist that can increase fluid removal and speed the return of effective oxygen exchange. This study aims to evaluate the safety and efficacy of nebulized albuterol as an adjuvant therapy in patients with acute anticholinesterase poisoning. This stratified block randomized, single-blinded, placebo-controlled, parallel-group clinical trial was conducted between November 2020 and October 2021. It enrolled 80 patients with acute anticholinesterase pesticide poisoning who were admitted to Tanta University Poison Control Center. Patients were allocated into two groups (40 patients each). The strata were based on the severity of poisoning (moderate and severe). Patients in group I received 10 mg of nebulized albuterol. Group II received an equivalent volume of nebulized normal saline. Additionally, standard treatment was provided to both groups. Outcomes included oxygenation, mortality, need for endotracheal intubation and mechanical ventilation, hospital stay duration, time to atropinization, and total doses of atropine and oxime. We found insignificant differences in sociodemographics, exposure characteristics, clinical manifestations, or routine laboratory tests between the studied groups. The median values of oxygen saturation by pulse oximetry were 99% in the albuterol moderate toxicity group and 98% in the control moderate toxicity group. Albuterol significantly improved oxygen saturation in moderate intoxicated patients (P = 0.039). Therefore, nebulized albuterol is a safe drug. Moreover, it may improve oxygenation in acute anticholinesterase pesticide poisoning.

In this study COVID-19 effects on different aspects of life that how this virus created a mess in every discipline of life starting from a small tuck shop of a street to a huge business with a chain between different countries; and some preventive measures are also suggested. Not only mental healthiness as well as physical health of people was also disturbed to a large extent. People being quarantined did not do any practice and had nothing to do, their boredom made them mentally and physically inactive. For minimization the effect of this pandemic on mental healthiness, interventions were practiced and psychological support systems were developed to help mentally effected people; on the other hand, to improve physical health the hospital workers worked day and night in return they got affected too either mentally or physically. Many of the youngsters started alcohol consumption during quarantine. Because of the closure of educational institutes, the students were sent back to their homes where there was no proper guidance for them and they lost their interests in studies; and in a sense educational impact of COVID-19 was also unbearable. Agricultural system was affected badly and the whole world passed through a huge economic loss. The flights and traffic were blocked throughout the world, and it is the only positive impact that COVID-19 led to the environment by improving water and air quality as there was a remarkable reduction in the emission of greenhouse gases.

Background: Aluminum, a well-recognized neurotoxin, is implicated in various neurodegenerative disorders. Moringa oleifera (M. oleifera), known as a miracle tree, is utilized as a functional food and nutritional supplement. This study investigates the potential preventive effects of M. oleifera extract on aluminum chloride (AlCl3)-induced cortical neurodegeneration in rats.

Materials and methods: Therefore, 24 adult male Wistar rats were randomly divided into four distinct groups: negative control, M. oleifera extract (MOE), AlCl3, and AlCl3 + MOE. Treatments were administered orally for 28 consecutive days. Cognitive performance, brain oxidative/nitrosative stress, neuroinflammation, apoptotic-cell death, and associated histopathological alterations were assessed.

Results: Our results showed that MOE improved spatial learning and memory, enhanced antioxidant superoxide dismutase enzyme activity, antagonized nitrosative stress, reduced inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), decreased caspase-3, increased Bcl-2, and facilitated repair of cortical and hippocampal structures.

Conclusions: We concluded that MOE exhibits protective effects against cortical neurodegeneration, making it a promising supplement to counteract aluminum-induced neurotoxic effects.

[This corrects the article DOI: 10.1093/toxres/tfad060.].

Background: Fine particulate matter (PM_2.5) exposure has been closely associated with cardiovascular diseases, which are relevant to cell cycle arrest. Brain and muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) not only participates in regulating the circadian clock but also plays a role in modulating cell cycle. However, the precise contribution of the circadian clock gene BMAL1 to PM_2.5-induced cell cycle change remains unclear. This study aims to explore the impact of PM_2.5 exposure on BMAL1 expression and the cell cycle in human umbilical vein endothelial cells (HUVECs).

Methods: HUVECs was exposed to PM_2.5 for 24 hours at different concentrations ((0, 12.5, 25, 75 and 100 μg.mL-1) to elucidate the potential toxic mechanism. Following exposure to PM_2.5, cell viability, ROS, cell cycle, and the expression of key genes and proteins were detected.

Results: A remarkable decrease in cell viability is observed in the PM_2.5-exposed HUVECs, as well as a significant increase in ROS production. In addition, PM_2.5-exposed HUVECs have cycle arrest in G0/G1 phase, and the gene expression of p27 is also markedly increased. The protein expression of BMAL1 and the gene expression of BMAL1 are increased significantly. Moreover, the protein expressions of p-p38 MAPK and p-ERK1/2 exhibit a marked increase in the PM_2.5-exposed HUVECs. Furthermore, following the transfection of HUVECs with siBMAL1 to suppress BMAL1 expression, we observed a reduction in both the protein and gene expression of the MAPK/ERK pathway in HUVECs exposed to PM_2.5.

Conclusions: Overall, our results indicate that PM_2.5 exposure significantly upregulates the circadian clock gene expression of BMAL1 and regulates G0/G1 cell cycle arrest in HUVECs through the MAPK/ERK pathway, which may provide new insights into the potential molecular mechanism regarding BMAL1 on PM_2.5-induced cardiovascular diseases.

With the aim of persistence property analysis and ecotoxicological impact of veterinary pharmaceuticals on different terrestrial species, different classes of veterinary pharmaceuticals (n = 37) with soil degradation property (DT₅₀) were gathered and subjected to QSAR and q-RASAR model development. The models were developed from 2D descriptors under organization for economic cooperation and development guidelines with the application of multiple linear regressions along with genetic algorithm. All developed QSAR and q-RASAR were statistically significant (Internal = R²_adj: 0.721-0.861, Q²_LOO: 0.609-0.757, and external = Q²F_n = 0.597-0.933, MAE_ext = 0.174-0.260). Further, the leverage approach of applicability domain assured the model's reliability. The veterinary pharmaceuticals with no experimental values were classified based on their persistence level. Further, the terrestrial toxicity analysis of persistent veterinary pharmaceuticals was done using toxicity prediction by computer assisted technology and in-house built quantitative structure toxicity relationship models to prioritize the toxic and persistent veterinary pharmaceuticals. This study will be helpful in estimation of persistence and toxicity of existing and upcoming veterinary pharmaceuticals.