Journals Journal of Applied Toxicology ...

Journal of Applied Toxicology : JAT
Wenwen Zhuang, Seo-Yeong Mun, Minju Park, Junsu Jeong, Hye Ryung Kim, Hongzoo Park, Eun-Taek Han, Jin-Hee Han, Wanjoo Chun, Hongliang Li, Won Sun Park
Voltage-dependent K+ (Kv) channels play an important role in restoring the membrane potential to its resting state, thereby maintaining vascular tone. In this study, native smooth muscle cells from rabbit coronary arteries were used to investigate the inhibitory effect of quetiapine, an atypical antipsychotic agent, on Kv channels. Quetiapine showed a concentration-dependent inhibition of Kv channels, with an IC50 of 47.98 ± 9.46 μM. Although quetiapine (50 μM) did not alter the steady-state activation curve, it caused a negative shift in the steady-state inactivation curve...
May 26, 2024: Journal of Applied Toxicology: JAT
Yan Wang, Liping Wei, Yuan Liu, Cheng Liu, Minbo Hou, Lu Zhou, Le Wang, Hua Li, Yunliang Qiu, JingMa
Legubicin is a novel conjugate of doxorubicin and a legumain-cleavable peptide linker. It has been developed to ameliorate the side effects of doxorubicin. Biodistribution in tumor-bearing mice, acute tolerance, and potential systemic toxic effects in Sprague-Dawley rats and beagle dogs of legubicin were assessed. Legubicin exists mainly as a protein complex in plasma after entering the circulation. Compared with conventional doxorubicin at an equal molar dose in mice, we found higher exposure to doxorubicin in tumor (approximately 1...
May 23, 2024: Journal of Applied Toxicology: JAT
Xiaodong Liu, Tianyi Jiang, Huiyun Jin, Chenxi Yan, Yuqi Tong, Jiaquan Ding, Yaqi Li, Lian Huang, Zhaohui Zhang
Beryllium sulfate (BeSO4 ) can cause inflammation through the mechanism, which has not been elucidated. Mitochondrial DNA (mtDNA) is a key contributor of inflammation. With mitochondrial damage, released mtDNA can bind to specific receptors (e.g., cGAS) and then activate related pathway to promote inflammatory responses. To investigate the mechanism of mtDNA in BeSO4 -induced inflammatory response in 16HBE cells, we established the BeSO4 -induced 16HBE cell inflammation model and the ethidium bromide (EB)-induced ρ0 16HBE cell model to detect the mtDNA content, oxidative stress-related markers, mitochondrial membrane potential, the expression of the cGAS-STING pathway, and inflammation-related factors...
May 22, 2024: Journal of Applied Toxicology: JAT
Ümit Acar, Burak Evren İnanan, Fahriye Zemheri-Navruz
Plastics are ubiquitous in modern society due to their cost-effectiveness, lightweight nature, and versatility. However, their extensive use and inadequate recycling have led to a significant environmental challenge, with plastic waste accumulating rapidly and causing ecological and health problems, especially in aquatic environments. Nanoplastics, particles ranging from 1 to 100 nm, have emerged as a particularly concerning subset due to their ability to easily penetrate biological barriers and accumulate in tissues...
May 22, 2024: Journal of Applied Toxicology: JAT
Xiaoyan Duan, Wanting Bai, Jiahuan Hu, Jinjin Wu, Huixin Tan, Fenghe Wang, Xuli Lang, Baolian Wang, Jinping Hu
Multidrug and toxin extrusion protein 1 (MATE1), an efflux transporter mainly expressed in renal proximal tubules, mediates the renal secretion of organic cationic drugs. The inhibition of MATE1 will impair the excretion of drugs into the tubular lumen, leading to the accumulation of nephrotoxic drugs in the kidney and consequently potentiating nephrotoxicity. Screening and identifying potent MATE1 inhibitors can predict or minimize the risk of drug-induced kidney injury. Flavonoids, a group of polyphenols commonly found in foodstuffs and herbal products, have been reported to cause transporter-mediated food/herb-drug interactions...
May 17, 2024: Journal of Applied Toxicology: JAT
Leila Najafi, Zia Moasses, Soghra Bahmanpour
The marijuana is considered as widely used recreational illicit drug that has become popular among women of reproductive age. It is believed that the marijuana use may have negative impacts on the female fertility. However, the exact mechanisms of its reproductive toxicity remain unclear. The studies suggest that the exogenous cannabinoids may interfere with endocannabinoid system and disrupt hypothalamic-pituitary-ovary axis. Consequently, it impacts the female fertility by disruption of normal secretion of ovarian sex hormones and menstrual cycles...
May 16, 2024: Journal of Applied Toxicology: JAT
Acharya Balkrishna, Sandeep Sinha, Kunal Bhattacharya, Anurag Varshney
A pre-clinical toxicological evaluation of herbal medicines is necessary to identify any underlying health-associated side effects, if any. BPGrit is an Ayurveda-based medicine prescribed for treating hypertensive conditions. High-performance liquid chromatography-based analysis revealed the presence of gallic acid, ellagic acid, coumarin, cinnamic acid, guggulsterone E, and guggulsterone Z in BPGrit. For sub-acute toxicity analysis of BPGrit, male and female Sprague-Dawley rats were given repeated oral gavage at 100, 300, and 1000 mg/kg body weight/day dosages for 28 days, followed by a 14-day recovery phase...
May 13, 2024: Journal of Applied Toxicology: JAT
Jangrez Khan, Nicholas D Kim, Collette Bromhead, Penelope Truman, Marlena C Kruger, Beth L Mallard
The food additive E171 (titanium dioxide, TiO2 ), is widely used in foods, pharmaceuticals and cosmetics. It is a fine white powder, with at least one third of its particles sized in the nanoparticulate (˂100 nm range, TiO2 NPs). The use of E171 is controversial as its relevant risk assessment has never been satisfactorily accomplished. In vitro and in vivo studies have shown dose-dependent toxicity in various organs including the liver. TiO2 NPs have been shown to induce inflammation, cell death and structural and functional changes within the liver...
May 13, 2024: Journal of Applied Toxicology: JAT
Lina Thors, Elisabeth Wigenstam, Johanna Qvarnström, Pär Wästerby, Linda Öberg, Anders Bucht
In a chemical mass casualty incident requiring skin decontamination, dry removal using absorbent materials may be beneficial to enable immediate decontamination. The efficacy of absorbent materials has therefore been evaluated, alone or procedures including both dry and wet decontamination, following skin exposure to two low volatile toxic chemicals using an in vitro human skin penetration model. Additionally, removal using active carbon wipes was evaluated with or without the Dahlgren Decon solution. All dry decontamination procedures resulted in a significantly decreased skin penetration rate of the industrial chemical 2-butoxyethanol compared to the control without decontamination...
May 10, 2024: Journal of Applied Toxicology: JAT
Katharina Klinzing, Ida Aabrandt Søndergaard, Teresa Chirom, James Whitwell, Laura Bisini, Cristina Marabottini, Fabrice Nesslany, Petri Tervasmäki, Juha-Pekka Pitkänen
One way of limiting the environmental impact of food production and improving food security is to replace part of the animal- or plant-based protein in the human diet with protein sourced from microorganisms. The recently discovered bacterium Xanthobacter sp. SoF1 (VTT-E-193585) grows autotrophically using carbon dioxide gas as the only carbon source, yielding protein-rich biomass that can be processed further into a powder and incorporated into various food products. Since the safety of this microbial protein powder for human consumption had not been previously assessed, its genotoxic potential was evaluated employing three internationally recognized and standardized studies: a bacterial reverse mutation test, an in vitro chromosomal aberration assay in human lymphocytes, and an in vitro micronucleus test in human lymphocytes...
May 10, 2024: Journal of Applied Toxicology: JAT
Xiugong Gao, Kayla Campasino, Miranda R Yourick, Yu Cao, Jeffrey J Yourick, Robert L Sprando
Dietary supplements containing usnic acid have been increasingly marketed for weight loss over the past decades, even though incidences of severe hepatotoxicity and acute liver failure due to their overuse have been reported. To date, the toxic mechanism of usnic acid-induced liver injury at the molecular level still remains to be fully elucidated. Here, we conducted a transcriptomic study on usnic acid using a novel in vitro hepatotoxicity model employing human induced pluripotent stem cell (iPSC)-derived hepatocytes...
May 9, 2024: Journal of Applied Toxicology: JAT
Kelly Yoshizaki, Daniela Perroni Frias, Kevin Maier, Juliana Smelan, Aristides Tadeu Correia, Luanda Mara da Silva Oliveira, Luís Fernando Amato-Lourenço, Bruna Tereso Santillo, Carla Máximo Prado, Telma Miyuki Oshiro, Jose Alexandre M Barbuto, Thais Mauad, Mariangela Macchione
The prevalence of fragrances in various hygiene products contributes to their sensorial allure. However, fragrances can induce sensitization in the skin or respiratory system, and the mechanisms involved in this process are incompletely understood. This study investigated the intricate mechanisms underlying the fragrance's effects on sensitization response, focusing on the interplay between CYP450 enzymes, a class of drug-metabolizing enzymes, and the adaptive immune system. Specifically, we assessed the expression of CYP450 enzymes and cytokine profiles in culture of BEAS-2B and mature dendritic cells (mDC) alone or in co-culture stimulated with 2 mM of a common fragrance, cinnamyl alcohol (CA) for 20 h...
May 7, 2024: Journal of Applied Toxicology: JAT
Divya Sangeetha Rajkumar, Rajashree Padmanaban
Dental resin systems, used for artificial replacement of teeth and their surrounding structures, have gained popularity due to the Food and Drug Administration's (FDA) recommendation to reduce dental amalgam use in high-risk populations and medical circumstances. Bisphenol A (BPA), an endocrine-disrupting chemical, is an essential monomer within dental resin in the form of various analogues and derivatives. Leaching of monomers from resins results in toxicity, affecting hormone metabolism and causing long-term health risks...
May 6, 2024: Journal of Applied Toxicology: JAT
Hongxia Lu, Xulei Zuo, Jiayu Yuan, Zhuoying Xie, Lihong Yin, Yuepu Pu, Zaozao Chen, Juan Zhang
Toxicological assessment of chemicals is crucial for safeguarding human health and the environment. However, traditional animal experiments are associated with ethical, technical, and predictive limitations in assessing the toxicity of chemicals to the skin. With the recent development of bioengineering and tissue engineering, three-dimensional (3D) skin models have been commonly used as an alternative for toxicological studies. The skin consists of the subcutaneous, dermis, and epidermis. All these layers have crucial functions such as physical and biological protection and thermoregulation...
May 6, 2024: Journal of Applied Toxicology: JAT
Oskari J Uski, Gregory D Rankin, Håkan Wingfors, Roger Magnusson, Christoffer Boman, Ala Muala, Anders Blomberg, Jenny Bosson, Thomas Sandström
In urban areas, inhalation of fine particles from combustion sources such as diesel engines causes adverse health effects. For toxicity testing, a substantial amount of particulate matter (PM) is needed. Conventional sampling involves collection of PM onto substrates by filtration or inertial impaction. A major drawback to those methodologies is that the extraction process can modify the collected particles and alter their chemical composition. Moreover, prior to toxicity testing, PM samples need to be resuspended, which can alter the PM sample even further...
May 5, 2024: Journal of Applied Toxicology: JAT
Zhi Huang, Mo Lin, Lei Wang, Liangding Dou, Xin Hou, Jinwen Zhang, Yongchao Huang, Lifang Wei, Ran An, Dai Wang, Youliang Yao, Dongbei Guo, Zhibo Li, Yongxing Zhang
This study demonstrated that both copper oxide nanoparticles (CuO-NPs) and copper nanoparticles (Cu-NPs) can cause swelling, inflammation, and cause damage to the mitochondria of alveolar type II epithelial cells in mice. Cellular examinations indicated that both CuO-NPs and Cu-NPs can reduce cell viability and harm the mitochondria of human bronchial epithelial cells, particularly Beas-2B cells. However, it is clear that CuO-NPs exhibit a more pronounced detrimental effect compared with Cu-NPs. Using bafilomycin A1 (Bafi A1), an inhibitor of lysosomal acidification, was found to enhance cell viability and alleviate mitochondrial damage caused by CuO-NPs...
May 3, 2024: Journal of Applied Toxicology: JAT
Saura C Sahu
The 21st-century toxicity testing program recommends the use of cytotoxicity data from human cells in culture for rapid in vitro screening focusing on biological pathways of potential toxicants to predict in vivo toxicity. Liver is the major organ for both endogenous and exogenous chemical metabolism of xenobiotics. Therefore, this review was undertaken to evaluate side by side five different currently used commercial cytotoxicity assay kits for purpose of rapid predictive screening of potential hepatotoxicants...
April 30, 2024: Journal of Applied Toxicology: JAT
Ying Li, Yan Sun, Jianghong Wang, Xiaolong Wang, Wenjie Yang
Voacangine, a naturally occurring alkaloid, has been testified to display beneficial effects on a variety of human diseases, but its role in ischemic stroke is unclear. The impacts of voacangine on oxygen-glucose deprivation/reoxygenation (OGD/R)-tempted hippocampal neuronal cells are investigated. The bioinformatics analysis found that voacangine is a bioactive ingredient that may have good effects on ischemic stroke. KEGG pathways analysis found that voacangine may regulate ischemic stroke through modulating the PI3K-Akt-FoxO signaling pathway...
April 26, 2024: Journal of Applied Toxicology: JAT
Yitong Liu, Michael Lawless, Miao Li, Kiara Fairman, Michelle R Embry, Constance A Mitchell
Botanicals contain complex mixtures of chemicals most of which lack pharmacokinetic data in humans. Since physicochemical and pharmacokinetic properties dictate the in vivo exposure of botanical constituents, these parameters greatly impact the pharmacological and toxicological effects of botanicals in consumer products. 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...
April 24, 2024: Journal of Applied Toxicology: JAT
Abdullah Al Sultan, Zahra Rattray, Nicholas J W Rattray
Thiazolidinediones (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...
April 23, 2024: Journal of Applied Toxicology: JAT
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