Identification of genes showing altered DNA methylation and gene expression in the renal proximal tubular cells of rats treated with ochratoxin A for 13 weeks
In conclusion, a variety of genes engaged in carcinogenic processes were obtained by epigenetic gene profiling in rat renal tubular cells specific to OTA treatment for 13 weeks. (Source: Journal of Applied Toxicology)
Source: Journal of Applied Toxicology - May 10, 2023 Category: Toxicology Authors: Shunsuke Ozawa, Ryota Ojiro, Qian Tang, Xinyu Zou, Gye ‐Hyeong Woo, Toshinori Yoshida, Makoto Shibutani Tags: RESEARCH ARTICLE Source Type: research

Evaluation of in vitro cytotoxic and genotoxic effects of the 3 ‐(3,4‐dihydroxyphenyl)‐8‐hydroxycoumarin
AbstractA wide variety of natural and synthetic coumarins present therapeutic potential. Therefore, the assessment of their safety for humans is essential. 3-(3,4-Dihydroxyphenyl)-8-hydroxycoumarin is a coumarin derivative with antioxidant properties, among other biological activities. The aim of this study is to evaluate the cytotoxic and genotoxic potential of this molecule on peripheral blood mononuclear cells (PBMC) and human hepatocellular carcinoma cells (HepG2/C3A). The results obtained for the cytotoxicity assays, evaluated by the trypan blue staining assay, using concentrations between 0.1 and 20  μg/mL, showed...
Source: Journal of Applied Toxicology - May 9, 2023 Category: Toxicology Authors: Edvannia Santos Silva, Maria Jo ão Matos, Edson Luis Maistro 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 - May 8, 2023 Category: Toxicology Tags: ISSUE INFORMATION Source Type: research

In silico prediction of hERG blockers using machine learning and deep learning approaches
In this study, a dataset containing 4556 compounds with IC50 values determined by patch clamp techniques on mammalian lineage cells was collected, and hERG blockers and non-blockers were distinguished according to three single thresholds and two binary thresholds. Four machine learning (ML) algorithms combining four molecular fingerprints and molecular descriptors as well as graph convolutional neural networks (GCNs) were used to construct a series of binary classification models. The results showed that the best models varied for different thresholds. The ML models implemented by support vector machine and random forest p...
Source: Journal of Applied Toxicology - May 6, 2023 Category: Toxicology Authors: Yuanting Chen, Xinxin Yu, Weihua Li, Yun Tang, Guixia Liu Tags: RESEARCH ARTICLE Source Type: research

Characteristics of transcription profile, adhesion and migration of SETD2 ‐loss Met‐5A mesothelial cells exposed with crocidolite
AbstractAsbestos is fibrous silicate mineral exhibiting biopersistence and carcinogen property and contribute to mesothelioma. Despite the concept of gene-environmental interaction in pathogenesis of mesothelioma, the possible pathophysiological changes of mesothelial cells simultaneously with SETD2 loss and asbestos exposure remains obscure. Herein, CRISPR/Cas9-mediated SETD2 knockout Met-5A mesothelial cells (Met-5ASETD2-KO) were established and exposed with crocidolite, an amphibole asbestos. Cell viability of Met-5ASETD2-KO appeared to dramatically decrease with ≥ 2.5 μg/cm2 crocidolite exposure as compared to Met-5...
Source: Journal of Applied Toxicology - May 6, 2023 Category: Toxicology Authors: Dan Yang, Chiyun Chen, Hailing Xia, Junqiang Chen, Min Yu Tags: RESEARCH ARTICLE Source Type: research

Magnetized vermiculite as a tool for the treatment of produced water generated by oil companies: Effects on aquatic organisms before and after treatment
AbstractProduced water (PW) generated by oil companies is a highly impacting waste that contains chemicals such as metals and organic and inorganic compounds. Given its polluting potential, PW requires effective treatment before being discharged into the environment. Conventional treatments have limited efficiency in removing PW toxicity, so alternative approaches must be developed and standardized. In this context, treatment with adsorbent materials like magnetized vermiculite (VMT-mag) is highlighted. This work aimed to evaluate the efficiency of treatment with VMT-mag in reducing PW toxicity to aquatic biota. For this p...
Source: Journal of Applied Toxicology - May 4, 2023 Category: Toxicology Authors: Tais S. Viana, Diana Campos, Mariana Bartilotti, Fernanda G. Leite, Maria Valnice Zanoni, Daniel J. Dorta, Danielle P. Oliveira, Jo ão L. T. Pestana Tags: RESEARCH ARTICLE Source Type: research

Development of a yeast reporter gene assay to detect ligands of freshwater cladoceran Daphnia magna ultraspiracle, a homolog of vertebrate retinoid X receptors
AbstractEndocrine-disrupting chemicals (EDCs) often affect homeostatic regulation in living organisms by directly acting on nuclear receptors (NRs). Retinoid X receptors (RXRs), the most highly conserved members of the NR superfamily during evolution, function as partners to form heterodimers with other NRs, such as retinoic acid, thyroid hormone, and vitamin D3 receptors. RXRs also homodimerize and induce the expression of target genes upon binding with their natural ligand, 9-cis-retinoic acid (9cRA), and typical EDCs organotin compounds, such as tributyltin and triphenyltin. In the present study, we established a new ye...
Source: Journal of Applied Toxicology - May 4, 2023 Category: Toxicology Authors: Sayoko Ito ‐Harashima, Yumiko Tsubouchi, Eiji Takada, Masanobu Kawanishi, Takashi Yagi Tags: RESEARCH ARTICLE Source Type: research

Inhibitory interaction of flavonoids with organic cation transporter 2 and their structure –activity relationships for predicting nephroprotective effects
This study aimed to screen potential inhibitors of OCT2 from 96 flavonoids, assess the nephroprotective effects on cisplatin-induced kidney injury, and clarify the structure–activity relationships of flavonoids with OCT2. Ten flavonoids exhibited significant inhibition (>50%) on OCT2 in OCT2-HEK293 cells. Among them, the six most potent flavonoid inhibitors, including pectolinarigenin, biochanin A, luteolin, chrysin, 6-hydroxyflavone, and 6-methylflavone markedly decreased cisplatin-induced cytotoxicity. Moreover, in cisplatin-induced renal injury models, they also reduced serum blood urea nitrogen (BUN) and creatinin...
Source: Journal of Applied Toxicology - May 3, 2023 Category: Toxicology Authors: Huixin Tan, Fenghe Wang, Jiahuan Hu, Xiaoyan Duan, Wanting Bai, Xinbo Wang, Baolian Wang, Yan Su, Jinping Hu Tags: RESEARCH ARTICLE Source Type: research

Magnetized vermiculite as a tool for the treatment of produced water generated by oil companies: Effects on aquatic organisms before and after treatment
AbstractProduced water (PW) generated by oil companies is a highly impacting waste that contains chemicals such as metals and organic and inorganic compounds. Given its polluting potential, PW requires effective treatment before being discharged into the environment. Conventional treatments have limited efficiency in removing PW toxicity, so alternative approaches must be developed and standardized. In this context, treatment with adsorbent materials like magnetized vermiculite (VMT-mag) is highlighted. This work aimed to evaluate the efficiency of treatment with VMT-mag in reducing PW toxicity to aquatic biota. For this p...
Source: Journal of Applied Toxicology - May 3, 2023 Category: Toxicology Authors: Tais S. Viana, Diana Campos, Mariana Bartilotti, Fernanda G. Leite, Maria Valnice Boldrin Zanoni, Daniel J. Dorta, Danielle P. Oliveira, Jo ão L. T. Pestana Tags: RESEARCH ARTICLE Source Type: research

Inhibitory interaction of flavonoids with organic cation transporter 2 and their structure –activity relationships for predicting nephroprotective effects
This study aimed to screen potential inhibitors of OCT2 from 96 flavonoids, assess the nephroprotective effects on cisplatin-induced kidney injury, and clarify the structure–activity relationships of flavonoids with OCT2. Ten flavonoids exhibited significant inhibition (>50%) on OCT2 in OCT2-HEK293 cells. Among them, the six most potent flavonoid inhibitors, including pectolinarigenin, biochanin A, luteolin, chrysin, 6-hydroxyflavone, and 6-methylflavone markedly decreased cisplatin-induced cytotoxicity. Moreover, in cisplatin-induced renal injury models, they also reduced serum blood urea nitrogen (BUN) and creatinin...
Source: Journal of Applied Toxicology - May 3, 2023 Category: Toxicology Authors: Huixin Tan, Fenghe Wang, Jiahuan Hu, Xiaoyan Duan, Wanting Bai, Xinbo Wang, Baolian Wang, Yan Su, Jinping Hu Tags: RESEARCH ARTICLE Source Type: research

2D ‐Quantitative structure–activity relationship modeling for risk assessment of pharmacotherapy applied during pregnancy
AbstractThe risk evaluation for pharmacological therapy during pregnancy is critical for maternal and fetal health. The initial risk assessment stage, the risk measurement, begins with pregnancy-labeling categories (A, B, C, D, and X) for pharmaceuticals defined by the US Food and Drug Administration (FDA). Recently, in silico methods have been preferred in toxicology studies to eliminate ethical issues before conducting clinical toxicology studies and animal experiments. Quantitative structure –activity relationship (QSAR) modeling is one of the in silico methodologies. The research focuses on creating a QSAR model that...
Source: Journal of Applied Toxicology - May 2, 2023 Category: Toxicology Authors: Gul Karaduman, Feyza Kelleci Çelik Tags: RESEARCH ARTICLE Source Type: research

CDCT induced nephrotoxicity in rat by apoptosis via metabolic disturbance
This study aims to investigate the CDCT-induced changes of morphology in kidney and metabolites, and further explore the possible mechanisms of CDCT-induced nephrotoxicity.Sprague-Dawley rats were exposed to the CDCT at a clinical equivalent dose for 6 days. CDCT exposure can induce kidney injury and death. Pathological changes, including creatinine, urea nitrogen and histopathology, were observed in rats. Furthermore, metabolomic-driven energy and glycerophospholipid metabolism pathway disorders, accompanied by remarkably changed key metabolites, such as succinate, leukotriene B4 (LTB4) and cardiolipin (CL), are observed ...
Source: Journal of Applied Toxicology - May 2, 2023 Category: Toxicology Authors: Chijing Zuo, Yan Liu, Jie Wang, Weidong Yu, Yujie Liu, Yanyan Zhang, Jingjing Xu, Daiyin Peng, Can Peng Tags: RESEARCH ARTICLE Source Type: research

Evaluation of in vitro Cytotoxic and Genotoxic Effects of the 3 ‐(3,4‐Dihydroxyphenyl)‐8‐hydroxycoumarin
AbstractA wide variety of natural and synthetic coumarins present therapeutic potential. Therefore, the assessment of their safety for humans is essential. 3-(3,4-Dihydroxyphenyl)-8-hydroxycoumarin is a coumarin derivative with antioxidant properties, amongst other biological activities. The aim of this study is to evaluate the cytotoxic and genotoxic potential of this molecule on peripheral blood mononuclear cells (PBMC) and human hepatocellular carcinoma cells (HepG2/C3A). The results obtained for the cytotoxicity assays, evaluated by the trypan blue staining assay, using concentrations between 0.1 and 20 μg/mL, showed ...
Source: Journal of Applied Toxicology - April 29, 2023 Category: Toxicology Authors: Edvannia Santos Silva, Maria Jo ão Matos, Edson Luis Maistro Tags: RESEARCH ARTICLE Source Type: research

Predicting binding between 55 cannabinoids and 4799 biological targets by in silico methods
AbstractRecently, there has been an increase in cannabis derived products being marketed as foods, dietary supplements, and other consumer products. Cannabis contains over a hundred cannabinoids, many of which have unknown physiological effects. Since there are large numbers of cannabinoids, and many are not commercially available, anin silico tool (Chemotargets Clarity software) was used to predict binding between 55 cannabinoids and 4799 biological targets (enzymes, ion channels, receptors, and transporters). This tool relied on quantitative structure activity relationships (QSAR), structural similarity, and other approa...
Source: Journal of Applied Toxicology - April 27, 2023 Category: Toxicology Authors: Michael F. Santillo, Robert L. Sprando Tags: RESEARCH ARTICLE Source Type: research