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Journal Toxicol. Appl. Pharmacol.

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Role of long non-coding RNAs and MYC interaction in cancer metastasis: A possible target for therapeutic intervention.

Homa Fatma, Hifzur R Siddique,

The c-MYC is one of the most commonly discussed oncogenes in almost all cancers. c-MYC, as a proto-oncogene in normal cells, has found to be tightly controlled and regulated, both genetically and epigenetically. Evasion of the controlled checkpoint mechanisms during cancer causes a deregulated expression of c-MYC. Overexpression of c-MYC ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, :115056]

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PBPK modeling of impact of nonalcoholic fatty liver disease on toxicokinetics of perchloroethylene in mice.

Chimeddulam Dalaijamts, Joseph A Cichocki, Yu-Syuan Luo, Ivan Rusyn, Weihsueh A Chiu,

BACKGROUND:Nonalcoholic fatty liver disease (NAFLD), a major cause of chronic liver disease in the Western countries with increasing prevalence worldwide, may substantially affect chemical toxicokinetics and thereby modulate chemical toxicity. OBJECTIVES:This study aims to use physiologically-based pharmacokinetic (PBPK) modeling to characterize the impact of NAFLD on toxicokinetics of perchloroethylene (perc). ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, :115069]

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Eprinomectin, a novel avermectin macrocylic lactone is cytotoxic to PC3 metastatic prostate cancer cells via inducing apoptosis.

Angela Lincy Prem Antony Samy, Velavan Bakthavachalam, Mona Vudutha, Smita Vinjamuri, Somaiah Chinnapaka, Gnanasekar Munirathinam,

Prostate Cancer (PCa) is the second most common cancer among men in United States after skin cancer. Conventional chemotherapeutic drugs available for PCa treatment are limited due to toxicity and resistance issues. Therefore, there is an urgent need to develop more effective treatment for advanced PCa. In this current study, ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, :115071]

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Effects of lithium on cytokine neuro-inflammatory mediators, Wnt/β-catenin signaling and microglial activation in the hippocampus of chronic mild stress-exposed rats.

Mohamed Z Habib, Mai A Ebeid, Yasser El Faramawy, Sherin S T Saad, Hekmat M El Magdoub, Azza A Attia, Sawsan Aboul-Fotouh, Ahmed M Abdel-Tawab,

Microglial in vivo production of pro-inflammatory cytokines is central to the pathogenesis of multiple neurological disorders including depression, with a rising role of Wnt/β-catenin signaling as potential regulator of microglia-mediated neuro-inflammation. This study aimed at investigating the hippocampal expression of the Wnt/ß-catenin pathway in chronic mild stress (CMS)-exposed rats and ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, :115073]

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MiR-122-5p increases radiosensitivity and aggravates radiation-induced rectal injury through CCAR1.

Yulong Ge, Wenzhi Tu, Junjun Li, Xuming Chen, Ying Chen, Yi Xu, Yiqing Xu, Yaming Wang, Yong Liu,

Radiation-induced rectal injury is a major side-effect observed in patients with pelvic malignancies who receive radiotherapy. MicroRNA (miRNA), involved in many cellular biological processes, can be disturbed by ionizing radiation (IR). In this study, we have investigated the function of microRNA-122-5p (miR-122-5p) in radiation-induced rectal injury. MiR-122-5p levels in the ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 399:115054]

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ATPR induces acute promyelocytic leukemia cells differentiation and growth arrest by blockade of SHP2/Rho/ROCK1 pathway.

Lanlan Li, Xiaoling Xu, Yan Du, Meiju Zhang, Yubin Feng, Xuewen Qian, Shufang Li, Tianxi Du, Xiaoqing Peng, Feihu Chen,

Acute promyelocytic leukemia (APL) is a form of acute myeloid leukemia with a unique chromosome translocation t (15;17), commonly complicated by a complex coagulopathy. 4-Amino-2-trifuoromethyl-phenyl retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative, was synthesized by our group and known to possess obvious biological anti-tumor activities. It has previously ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 399:115053]

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The circadian clock protects against acute radiation-induced dermatitis.

Panshak P Dakup, Kenneth I Porter, Shobhan Gaddameedhi,

Radiation-induced dermatitis is a common occurrence in cancer patients undergoing radiation therapy (RT) and is caused when ionizing radiation (IR) induces DNA strand breaks in skin cells. The wide use of RT in cancer treatments makes it important to minimize RT-induced toxicities including radiodermatitis. This study sought to determine if ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, :115040]

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Adipose tissue-liver crosstalk during pathologic changes caused by vinyl chloride metabolites in mice.

Brenna R Kaelin, Collin M McKenzie, Karl W Hempel, Anna L Lang, Gavin E Arteel, Juliane I Beier,

Volatile organic compounds (VOCs), such as vinyl chloride (VC), can be directly toxic at high concentrations. However, we have shown that 'nontoxic' exposures to VC and its metabolite chloroethanol (CE) enhances experimental non-alcoholic fatty liver disease (NAFLD), suggesting an unpredicted interaction. Importantly, VOC exposure has been identified as a potential ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, :115068]

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An implanted port-catheter system for repeated hepatic arterial infusion of low-density lipoprotein-docosahexaenoic acid nanoparticles in normal rats: A safety study.

Yuzhu Wang, Junjie Li, Indhumathy Subramaniyan, Goncalo Dias do Vale, Jaideep Chaudhary, Arnida Anwar, Mary Wight-Carter, Jeffrey G McDonald, William C Putnam, Tao Qin, Hongwei Zhang, Ian R Corbin,

BACKGROUND:In recent years, small animal arterial port-catheter systems have been implemented in rodents with reasonable success. The aim of the current study is to employ the small animal port-catheter system to evaluate the safety of multiple hepatic-artery infusions (HAI) of low-density lipoprotein-docosahexaenoic acid (LDL-DHA) nanoparticles to the rat liver. METHODS:Wistar ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, :115037]

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Overexpression of the constitutive androstane receptor and shaken 3D-culturing increase biotransformation and oxidative phosphorylation and sensitivity to mitochondrial amiodarone toxicity of HepaRG cells.

Vincent A van der Mark, Aziza A A Adam, Jung-Chin Chang, Ronald P Oude Elferink, Robert A F M Chamuleau, Ruurdtje Hoekstra,

The liver cell line HepaRG is one of the preferred sources of human hepatocytes for in vitro applications. However, mitochondrial energy metabolism is relatively low, which affects hepatic functionality and sensitivity to hepatotoxins. Culturing in a bioartificial liver (BAL) system with high oxygen, medium perfusion, low substrate stiffness, and 3D ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 399:115055]

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A QSAR study that compares the ability of bisdioxopiperazine analogs of the doxorubicin cardioprotective agent dexrazoxane (ICRF-187) to protect myocytes with DNA topoisomerase II inhibition.

Brian B Hasinoff, Daywin Patel, Xing Wu,

The cardiotoxicity caused by doxorubicin and extravasation injury caused by anthracyclines is reduced by the clinically approved bisdioxopiperazine drug dexrazoxane. Dexrazoxane is a rings-closed analog of EDTA and is hydrolyzed in vivo to a form that strongly binds iron. Its protective effects were originally thought to be due to the ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 399:115038]

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Corrigendum to "Sesamin suppresses NSCLC cell proliferation through cyclin D1 inhibition-dependent cell cycle arrest via Akt/p53 pathway" [Toxicology and applied pharmacology, 387 (2020) 114848].

Yueming Chen, Huachao Li, Weinan Zhang, Wanchen Qi, Changpeng Lu, Huiliang Huang, Zhicheng Yang, Bing Liu, Luyong Zhang,

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, :115048]

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Long-term mildronate treatment increased Proteobacteria level in gut microbiome, and caused behavioral deviations and transcriptome change in liver, heart and brain of healthy mice.

Artem P Gureev, Ekaterina A Shaforostova, Inna Yu Vitkalova, Irina S Sadovnikova, Yulia I Kalinina, Vadim R Cherednichenko, Karina A Reznikova, Valeria V Valuyskikh, Vasily N Popov,

Mildronate is a cardiac and neuroprotective drug that is widely used in some countries. By inhibiting carnitine biosynthesis, mildronate impairs the fatty acids transport into mitochondria, thereby decreasing the β-oxidation intensity. Since 2016, it has been prohibited by the World Anti-Doping Agency (WADA). However, the information on its safety and ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 398:115031]

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Luteolin prevents liver from tunicamycin-induced endoplasmic reticulum stress via nuclear factor erythroid 2-related factor 2-dependent sestrin 2 induction.

Kyung Hwan Jegal, Eun Ok Kim, Jae Kwang Kim, Sang Mi Park, Dae Hwa Jung, Gum Hwa Lee, Sung Hwan Ki, Sung Hui Byun, Sae Kwang Ku, Il Je Cho, Sang Chan Kim,

Endoplasmic reticulum (ER) stress designates a cellular response to the accumulation of misfolded proteins, which is related to disease progression in the liver. Luteolin (3',4',5,7-tetrahydroxyflavone) is a phytochemical found frequently in medicinal herbs. Although luteolin has been reported to possess the therapeutic potential to prevent diverse stage of liver diseases, ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 399:115036]

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Elucidation of OATP1B1 and 1B3 transporter function using transgenic rodent models and commonly known single nucleotide polymorphisms.

Supratim Choudhuri, Curtis D Klaassen,

The clearance of many drugs from the blood into the liver, such as the statins, is dependent on the organic anion transporting polypeptides (OATPs). Patients with *5 and *15 polymorphisms of OATP1B1 remove less of the statin as it traverses the liver and thus more reaches the rest of the ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 399:115039]

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Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor α.

Madeleine Böckers, Norbert W Paul, Thomas Efferth,

Plasticizers released from microplastic are increasingly viewed with concern. While adverse health effects induced by bisphenol A and its analogues on marine animals are well documented in the literature, the endocrine potential of bisphenolic compounds on human health remains elusive. We applied next generation sequencing (NGS) with the estrogen receptor ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 399:115030]

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Cholecystokinin-1 receptor agonist induced pathological findings in the exocrine pancreas of non-human primates.

Niels Chresten Berg Nyborg, Rikke Kaae Kirk, Anne Sietske de Boer, David Wederkinck Andersen, Anne Bugge, Birgitte Schjellerup Wulff, Inger Thorup, Trine Ryberg Clausen,

BACKGROUND AND AIMS:Cholecystokinin (CCK) may potentially be used to treat obesity. However, it is well-known to induce acute pancreatitis and pancreas neoplasia in rodents, but not in primates. Here we report the nonclinical safety profile of a long-acting CCK-1 receptor (CCK-1R) agonist, NN9056, in rats and monkeys to support a ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 399:115035]

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Irinotecan-mediated diarrhea is mainly correlated with intestinal exposure to SN-38: Critical role of gut Ugt.

Rongjin Sun, Lijun Zhu, Li Li, Wenjie Song, Xia Gong, Xiaoxiao Qi, Ying Wang, Romi Ghose, Song Gao, Ming Hu, Zhongqiu Liu,

BACKGROUND AND PURPOSE:Irinotecan-induced diarrhea (IID) results from intestinal damages by its active metabolite SN-38. Alleviation of these damages has focused on lowering luminal SN-38 concentrations. However, it is unclear if the enteric bioavailability of SN-38 is mostly dependent on luminal SN-38 concentrations. EXPERIMENTAL APPROACH:Irinotecan (50 mg/kg, i.p. once daily for 6 days) ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 398:115032]

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters hepatic polyunsaturated fatty acid metabolism and eicosanoid biosynthesis in female Sprague-Dawley rats.

Claire M Doskey, Kelly A Fader, Rance Nault, Todd Lydic, Jason Matthews, Dave Potter, Bonnie Sharratt, Kurt Williams, Tim Zacharewski,

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor (AhR) agonist that elicits a broad spectrum of dose-dependent hepatic effects including lipid accumulation, inflammation, and fibrosis. To determine the role of inflammatory lipid mediators in TCDD-mediated hepatotoxicity, eicosanoid metabolism was investigated. Female Sprague-Dawley (SD) rats were orally gavaged with sesame oil ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 398:115034]

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Anti-epileptic activity, toxicity and teratogenicity in CD1 mice of a novel valproic acid arylamide derivative, N-(2-hydroxyphenyl)-2-propylpentanamide.

José Melesio Cristóbal-Luna, José Correa-Basurto, Humberto L Mendoza-Figueroa, Germán Chamorro-Cevallos,

N-(2-hydroxyphenyl)-2-propylpentamide (HO-AAVPA) is a novel arylamide derivative of valproic acid (VPA) designed in silico, with better antioxidant and antiproliferative effect on cancer cell lines than VPA. This study was aimed to evaluate the anticonvulsant activity, the toxicity and teratogenicity produced in HO-AAVPA-treated CD1 mice using VPA as positive control. With ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 399:115033]

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Cognitive enhancing effect of diapocynin in D-galactose-ovariectomy-induced Alzheimer's-like disease in rats: Role of ERK, GSK-3β, and JNK signaling.

Weam W Ibrahim, Hesham M Ismail, Mahmoud M Khattab, Noha F Abdelkader,

NADPH oxidase (NOX) has been identified as a crucial contender of oxidative damage in Alzheimer's disease (AD). However, the capability of diapocynin, a NOX inhibitor, to offer neuroprotection in AD models is still a matter of debate. Hence, the current work is dedicated to investigate the influence of diapocynin on ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 398:115028]

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Investigating DNA adduct formation by flavor chemicals and tobacco byproducts in electronic nicotine delivery system (ENDS) using in silico approaches.

Jueichuan Connie Kang, Luis G Valerio,

The presence of flavors is one of the commonly cited reasons for use of e-cigarettes by youth; however, the potential harms from inhaling these chemicals and byproducts have not been extensively studied. One mechanism of interest is DNA adduct formation, which may lead to carcinogenesis. We identified two chemical classes ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 398:115026]

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Maternal-fetal disposition of domoic acid following repeated oral dosing during pregnancy in nonhuman primate.

Sara Shum, Jing Jing, Rebekah Petroff, Brenda Crouthamel, Kimberly S Grant, Thomas M Burbacher, Nina Isoherranen,

Domoic acid (DA) is a marine algal toxin that causes acute and chronic neurotoxicity in animals and humans. Prenatal exposure to DA has been associated with neuronal damage and cognitive and behavioral deficits in juvenile California sea lions, cynomolgus monkeys and rodents. Yet, the toxicokinetics (TK) of DA during pregnancy ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 398:115027]

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Metabolomic-based assessment reveals dysregulation of lipid profiles in human liver cells exposed to environmental obesogens.

Marco E Franco, Maria T Fernandez-Luna, Alejandro J Ramirez, Ramon Lavado,

Significant attention has been given to the potential of environmental chemicals to disrupt lipid homeostasis at the cellular level. These chemicals, classified as obesogens, are abundantly used in a wide variety of consumer products. However, there is a significant lack of information regarding the mechanisms by which environmental exposure can ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 398:115009]

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The selective c-Met inhibitor capmatinib offsets cisplatin-nephrotoxicity and doxorubicin-cardiotoxicity and improves their anticancer efficacies.

Mohamed E Shaker, Ahmed A Shaaban, Mohamed M El-Shafey, Mohamed E El-Mesery,

The incorporation of mesenchymal-epithelial transition factor (c-Met) inhibitors with conventional chemotherapeutics may increase the anticancer efficacy of chemotherapeutic agents, but bears the risk of enhancing the adverse effects. To test the hypothesis, co-administration of the novel c-Met inhibitor capmatinib with cisplatin (CIS) or doxorubicin (DOX) was investigated on nephrotoxicity and ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2020, 398:115018]

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