Prediction of physicochemical and pharmacokinetic properties of botanical constituents by computational models
This study sought to use computational (i.e., in silico) models, including quantitative structure –activity relationships (QSAR) and physiologically based pharmacokinetic (PBPK) modeling, to predict properties of botanical constituents. One hundred and three major constituents (e.g., withanolides, mitragynine, and yohimbine) in 13 botanicals (e.g., ashwagandha, kratom, and yohimbe) were invest igated. The predicted properties included biopharmaceutical classification system (BCS) classes based on aqueous solubility and permeability, oral absorption, liver microsomal clearance, oral bioavailability, and others. Over half ...
Source: Journal of Applied Toxicology - April 25, 2024 Category: Toxicology Authors: Yitong Liu,
Michael Lawless,
Miao Li,
Kiara Fairman,
Michelle R. Embry,
Constance A. Mitchell Tags: RESEARCH ARTICLE Source Type: research
Cytotoxicity and toxicoproteomics analysis of thiazolidinedione exposure in human ‐derived cardiomyocytes
AbstractThiazolidinediones (TZDs) (e.g. pioglitazone and rosiglitazone), known insulin sensitiser agents for type II diabetes mellitus, exhibit controversial effects on cardiac tissue. Despite consensus on their association with increased heart failure risk, limiting TZD use in diabetes management, the underlying mechanisms remain uncharacterised. Herein, we report a comprehensive in vitro investigation utilising a novel toxicoproteomics pipeline coupled with cytotoxicity assays in human adult cardiomyocytes to elucidate mechanistic insights into TZD cardiotoxicity. The cytotoxicity assay findings showed a significant loss...
Source: Journal of Applied Toxicology - April 24, 2024 Category: Toxicology Authors: Abdullah Al Sultan,
Zahra Rattray,
Nicholas J. W. Rattray Tags: RESEARCH ARTICLE Source Type: research
The multifaceted role of macrophage mitophagy in SiO2 ‐induced pulmonary fibrosis: A brief review
AbstractProlonged exposure to environments with high concentrations of crystalline silica (CS) can lead to silicosis. Macrophages play a crucial role in the pathogenesis of silicosis. In the process of silicosis, silica (SiO2) invades alveolar macrophages (AMs) and induces mitophagy which usually exists in three states: normal, excessive, and/or deficiency. Different mitophagy states lead to corresponding toxic responses, including successful macrophage repair, injury, necrosis, apoptosis, and even pulmonary fibrosis. This is a complex process accompanied by various cytokines. Unfortunately, the details have not been fully...
Source: Journal of Applied Toxicology - April 23, 2024 Category: Toxicology Authors: Yu ‐ting Zhou,
Shuang Li,
Shu‐ling Du,
Jia‐hui Zhao,
Ya‐qiong Cai,
Zhao‐qiang Zhang Tags: REVIEW ARTICLE Source Type: research
Mitophagy and its regulatory mechanisms in the biological effects of nanomaterials
AbstractMitophagy is a selective cellular process critical for the removal of damaged mitochondria. It is essential in regulating mitochondrial number, ensuring mitochondrial functionality, and maintaining cellular equilibrium, ultimately influencing cell destiny. Numerous pathologies, such as neurodegenerative diseases, cardiovascular disorders, cancers, and various other conditions, are associated with mitochondrial dysfunctions. Thus, a detailed exploration of the regulatory mechanisms of mitophagy is pivotal for enhancing our understanding and for the discovery of novel preventive and therapeutic options for these dise...
Source: Journal of Applied Toxicology - April 21, 2024 Category: Toxicology Authors: Rui Zhang,
Haitao Yang,
Menghao Guo,
Shuyan Niu,
Yuying Xue Tags: REVIEW ARTICLE Source Type: research
Atorvastatin ‐induced intracerebral hemorrhage is inhibited by berberine in zebrafish
In this study, we aimed to investigate the protective action and mechanisms of berberine (BBR) against ATV-induced brain hemorrhage. We established an ICH model in zebrafish induced by ATV (2 μM) and demonstrated the effects of BBR (10, 50, and 100 μM) on ICH via protecting the vascular network using hemocyte staining and three transgenic zebrafish. BBR was found to reduce brain inflammation and locomotion injury in ICH-zebrafish. Mechanism research showed that ATV increased the l evels of VE-cadherin and occludin proteins but disturbed their localization at the cell membrane by abnormal phosphorylation, which decre...
Source: Journal of Applied Toxicology - April 20, 2024 Category: Toxicology Authors: Xin ‐Yan Liu,
Bo Chen,
Rui Zhang,
Miao‐Qing Zhang,
Yuan‐Yuan Ma,
Ying Han,
Jian‐Dong Jiang,
Jing‐Pu Zhang Tags: RESEARCH ARTICLE Source Type: research
Comparing the effects and potencies of perchlorate and nitrate on amphibian metamorphosis using a modified amphibian metamorphosis assay (AMA)
AbstractA modified amphibian metamorphosis assay was performed in which Nieuwkoop and Faber (NF) stage 47Xenopus laevis larvae were exposed to different concentrations of either perchlorate (ClO4−) or nitrate (NO3−) for 32 days. Larvae were exposed to 0.0 (control), 5, 25, 125, 625, and 3125 μg/L ClO4−, or 0 (control), 23, 71, 217, 660, and 2000 mg/L NO3−. The primary endpoints were survival, hind limb length (HLL), forelimb emergence and development, developmental stage (including time to NF stage 62 [MT62]), thyroid histopathology, wet weight, and snout-vent length (SVL). Developmental delay as eviden...
Source: Journal of Applied Toxicology - April 19, 2024 Category: Toxicology Authors: Douglas J. Fort,
Brittanie F. Peake,
Michael B. Mathis,
M. Annegaaike Leopold,
Jeffrey C. Wolf,
Peter J. J. M. Weterings Tags: RESEARCH ARTICLE Source Type: research
Issue Information
No abstract is available for this article. (Source: Journal of Applied Toxicology)
Source: Journal of Applied Toxicology - April 15, 2024 Category: Toxicology Tags: ISSUE INFORMATION Source Type: research
Toxicity and inflammatory potential of mineral fibres: The contribute of released soluble metals versus cell contact direct effects
In conclusion, CHR represented the main pro-inflammatory trigger, able to recruit and activate circulating naïve monocytes, through its released metals, already in the first 24 h after inhalation. (Source: Journal of Applied Toxicology)
Source: Journal of Applied Toxicology - April 12, 2024 Category: Toxicology Authors: Vanessa Almonti,
Stefania Vernazza,
Serena Mirata,
Sara Tirendi,
Mario Passalacqua,
Alessandro Francesco Gualtieri,
Dario Di Giuseppe,
Sonia Scarf ì,
Anna Maria Bassi Tags: RESEARCH ARTICLE Source Type: research
Toxicology and safety study of L ‐tryptophan and its impurities for use in swine
This study was conducted in tertiary hybrid [(Landrace × Yorkshire) × Duroc] pigs to assess general toxicity and potential risks for EMS-related symptoms associated with L-tryptophan used as a feed additive. Our investigation elucidated the relationship between L-tr yptophan and EMS in swine. No mortalities or clinical signs were observed in any animals during the administration period, and the test substance did not induce toxic effects. Hematological analysis and histopathological examination revealed no changes in EMS-related parameters, such as eosinophil c ounts, lung lesions, skin lesions, or muscle atrophy...
Source: Journal of Applied Toxicology - April 10, 2024 Category: Toxicology Authors: Ji ‐Eun Park,
Soo Min Ko,
Hyo‐Jeong Han,
Ji‐Young Lee,
Da Som Jeong,
Dong Hyun Lee,
In Kyung Heo,
Yong Uk Shin,
Yang Hee Kim,
Woo‐Chan Son Tags: RESEARCH ARTICLE Source Type: research
Isobavachalcone induces hepatotoxicity in zebrafish embryos and HepG2 cells via the System Xc −‐GSH‐GPX4 signaling pathway in ferroptosis response
AbstractIsobavachalcone (IBC) is a flavonoid component of the traditional Chinese medicine Psoraleae Fructus, with a range of pharmacological properties. However, IBC causes some hepatotoxicity, and the mechanism of toxicity is unclear. The purpose of this paper was to investigate the possible mechanism of toxicity of IBC on HepG2 cells and zebrafish embryos. The results showed that exposure to IBC increased zebrafish embryo mortality and decreased hatchability. Meanwhile, IBC induced liver injury and increased expression of ALT and AST activity. Further studies showed that IBC caused the increase of ROS and MDA the decrea...
Source: Journal of Applied Toxicology - April 7, 2024 Category: Toxicology Authors: Xuan Ni,
Chen Gao,
Xiaolin Zhu,
Xiaosong Zhang,
Yizhuo Fang,
Zhihui Hao Tags: RESEARCH ARTICLE Source Type: research
Cytogenotoxic screening of the natural compound niga ‐ichigoside F1 from Rubus imperialis (Rosaceae)
AbstractRubus imperialis Chum. Schl. (Rosaceae) have demonstrated some pharmacological activities, including gastroprotective action. However, genotoxic effects ofR. imperialis extract was also reported. Since niga-ichigoside F1 (NIF1) is a major compound of this plant species, and which has proven pharmacological properties, it is essential to investigate whether this compound is responsible for the observed toxicity. Therefore, the objective of this study was to analyze the effects of NIF1 on HepG2/C3A cells for possible cytogenotoxicity, cell cycle and apoptosis influence, and expression of genes linked to the DNA damag...
Source: Journal of Applied Toxicology - April 4, 2024 Category: Toxicology Authors: La íza Moura Almeida‐Terassi,
Ana Paula Martins Castanha,
Greice Rafaele Alves,
Valdir Cechinel‐Filho,
Rivaldo Niero,
Isabel O'Neill de Mascarenhas Gaivão,
Liana Martins de Oliveira,
Luan Vitor Alves de Lima,
Mário Sérgio Mantovani,
Edson Tags: RESEARCH ARTICLE Source Type: research
Comparison of the sensitivity of histopathological and immunohistochemical analyses and blood hormone levels for early detection of antithyroid effects in rats treated with thyroid peroxidase inhibitors
AbstractAlthough measurements of blood triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels in rodent toxicity studies are useful for detection of antithyroid substances, assays for these measurements are expensive and can show high variability depending on blood sampling conditions. To develop more efficient methods for detecting thyroid disruptors, we compared histopathological and immunohistochemical findings in the thyroid and pituitary glands with blood hormone levels. Six-week-old male and female Sprague –Dawley rats (five rats per group) were treated with multiple doses of the thyroi...
Source: Journal of Applied Toxicology - April 3, 2024 Category: Toxicology Authors: Hirotoshi Akane,
Takeshi Toyoda,
Kohei Matsushita,
Tomomi Morikawa,
Tadashi Kosaka,
Hitoshi Tajima,
Hiroaki Aoyama,
Kumiko Ogawa Tags: RESEARCH ARTICLE Source Type: research
Evaluation of machine learning models for cytochrome P450 3A4, 2D6, and 2C9 inhibition
In this study, we systematically evaluated the conventional machine learning and deep learning models fo r three major P450 enzymes, CYP3A4, CYP2D6, and CYP2C9 from several perspectives, such as algorithms, molecular representation, and data partitioning strategies. Our results showed that the XGBoost and CatBoost algorithms coupled with the combined fingerprint/physicochemical descriptor features exhi bited the best performance with Area Under Curve (AUC) of 0.92, while the deep learning models were generally inferior to the conventional machine learning models (average AUC reached 0.89) on the same test sets. We also f...
Source: Journal of Applied Toxicology - March 28, 2024 Category: Toxicology Authors: Changda Gong,
Yanjun Feng,
Jieyu Zhu,
Guixia Liu,
Yun Tang,
Weihua Li Tags: RESEARCH ARTICLE Source Type: research
