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Microcystin-LR sensitizes the Oncorhynchus mykiss intestinal epithelium and interacts with paralytic shellfish toxins to alter oxidative balance Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-13 Julio C. Painefilú, Carolina González, Bernd Krock, Flavia Bieczynski, Carlos M. Luquet
In the context of harmful algal blooms, fish can be exposed to the combined effects of more than one toxin. We studied the effects of consecutive exposure to Microcystin-LR (MCLR) and paralytic shellfish toxins (PST) / (MCLR+PST) in the rainbow trout middle intestine. We fed juvenile fish with MCLR incorporated in the feed every 12 h and euthanized them 48 h after the first feeding. Immediately, we
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Transcriptomic analysis reveals particulate hexavalent chromium regulates key inflammatory pathways in human lung fibroblasts as a possible mechanism of carcinogenesis Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-11 J. Calvin Kouokam, Rachel M. Speer, Idoia Meaza, Jennifer H. Toyoda, Haiyan Lu, John Pierce Wise
Hexavalent chromium [Cr(VI)] is considered a major environmental health concern and lung carcinogen. However, the exact mechanism by which Cr(VI) causes lung cancer in humans remains unclear. Since several reports have demonstrated a role for inflammation in Cr(VI) toxicity, the present study aimed to apply transcriptomics to examine the global mRNA expression in human lung fibroblasts after acute
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Bronchioalveolar organoids: A preclinical tool to screen toxicity associated with antibody-drug conjugates Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-06 Tara N. McCray, Vy Nguyen, Jake S. Heins, Elizabeth Nguyen, Kristen Stewart, Colby T. Ford, Calvin Neace, Priyanka Gupta, David J. Ortiz
Despite extensive preclinical testing, cancer therapeutics can result in unanticipated toxicity to non-tumor tissue in patients. These toxicities may pass undetected in preclinical experiments due to modeling limitations involving poor biomimicry of 2-dimensional in vitro cell cultures and due to lack of interspecies translatability in in vivo studies. Instead, primary cells can be grown into miniature
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Downregulation of mesenteric afferent sensitivity following long-term systemic treatment of vincristine in mice Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-06 Shuang Li, Mengyuan Yang, Yao Shi, Jingxin Li, Chuanyong Liu
Gastrointestinal paresthesia and dysmotility are common side effects of vincristine (VCR) chemotherapy, which have become one of the factors for dose reduction, therapy delay or discontinuation. However, the mechanism is not entirely clear, whether it is related to autonomic nerves injury remains unknown. Therefore, we aimed to study whether VCR-induced gastrointestinal toxicity is related to changes
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The SMAC mimetic GDC-0152 is a direct ABCB1-ATPase activity modulator and BIRC5 expression suppressor in cancer cells Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-05 I-Li Lin, Yu-Ting Lin, Yung-Chieh Chang, Sree Karani Kondapuram, Kai-Hsuan Lin, Pin-Chen Chen, Chung-Ying Kuo, Mohane Selvaraj Coumar, Chun Hei Antonio Cheung
Upregulation of the multidrug efflux pump ABCB1/MDR1 (P-gp) and the anti-apoptotic protein BIRC5/Survivin promotes multidrug resistance in various human cancers. GDC-0152 is a DIABLO/SMAC mimetic currently being tested in patients with solid tumors. However, it is still unclear whether GDC-0152 is therapeutically applicable for patients with ABCB1-overexpressing multidrug-resistant tumors, and the
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Role of MST2/YAP1 signaling pathway in retinal cells apoptosis and diabetic retinopathy Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-05 Xiao Zhang, Dongmei Su, Dong Wei, Xiaoya Chen, Yuzhu Hu, Sijia Li, Yue Zhang, Xu Ma, Shanshan Hu, Zhaoyi Sun
Diabetic retinopathy (DR) is a main factor affecting vision of patients, and its pathogenesis is not completely clear. The purpose of our study was to investigate correlations between MST2 and DR progression, and to study the possible mechanism of MST2 and its down pathway in high glucose (HG)-mediated RGC-5 apoptosis. The diabetic rat model was established by intraperitoneal injection of streptozotocin
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Molecular docking, characterization, ADME/toxicity prediction, and anti-ulcer activity of new quercetin derivatives on indomethacin-induced gastric ulcer in mice Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-04 Maha B. Salem, Abdulrahman M. Saleh, Sayed H. Seif el-Din, Safia Samir, Olfat A. Hammam, Naglaa M. El-Lakkany
Gastric ulcer (GU) is a serious upper gastrointestinal tract disorder that affects people worldwide. The drugs now available for GU treatment have a high rate of relapses and drug interactions, as well as mild to severe side effects. As a result, new natural therapeutic medications for treating GU with fewer negative side effects are desperately needed. Because of quercetin's (QCT) diverse pharmacological
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Pinoresinol diglucoside mitigates dexamethasone-induced osteoporosis and chondrodysplasia in zebrafish Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-03 Yuhua Zuo, Chao Chen, Fasheng Liu, Hongmei Hu, Si Dong, Qinyuan Shen, Junquan Zeng, Ling Huang, Xinjun Liao, Zigang Cao, Zilin Zhong, Huiqiang Lu, Jianjun Chen
The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly. This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of , against dexamethasone-induced osteoporosis and chondrodysplasia. A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of
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Mechanisms of adverse mammary effect induced by olanzapine and therapeutic interventions in rat model. Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-02 Yingyue Dong, Xiaozhe Sun, Hanxiao Li, Chunmiao Han, Yue Zhang, Huiru Ding, Lisha Xia, Huamin Wang, Shaomin Yang, Lingzi Xu, Guoheng Xu
Olanzapine antagonizes dopamine receptors and is prescribed to treat multiple psychiatric conditions. The main side effect of concern for olanzapine is weight gain and metabolic syndrome. Olanzapine induces hyperprolactinemia, however its effect on the mammary gland is poorly documented. Rats received olanzapine by gavage or in drinking water at 1, 3, and 6 mg/kg/day for 5–40 days or 100 days, with
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Ondansetron attenuates cisplatin-induced behavioral and cognitive impairment through downregulation of NOD-like receptor inflammasome pathway Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-02 Mennat-Allah M. Hassan, Sara A. Wahdan, Reem N. El-Naga, Tamer M. Abdelghany, Ebtehal El-Demerdash
Cisplatin is an effective and commonly used chemotherapeutic drug; however, its use is accompanied by several adverse effects, including chemobrain. Ondansetron is a 5-HT3 antagonist, commonly used in prophylactic against chemotherapy-induced nausea and vomiting. Moreover, it has been identified as a novel neuroprotective agent in different animal models. However, its protective role against chemotherapy-induced
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Ursolic acid alleviates paclitaxel-induced peripheral neuropathy through PPARγ activation Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-02 Yulian Yang, Zhongzheng He, Shuangchan Wu
Chemotherapy-induced peripheral neuropathy (CIPN) reduces the overall quality of life and leads to interruption of chemotherapy. Ursolic acid, a triterpenoid naturally which presents in fruit peels and in many herbs and spices, can function as a peroxisome proliferator-activated receptor γ (PPARγ) agonist, and has been widely used as an herbal medicine with a wide spectrum of pharmacological activities
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Resveratrol alleviates inflammatory bowel disease by inhibiting JAK2/STAT3 pathway activity via the reduction of O-GlcNAcylation of STAT3 in intestinal epithelial cells Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-02 Zhang Yaqin, Wu Kehan, Zhu Yi, Wang Naijian, Qiu Wei, Mao Fei
The role of O-linked -acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) in the pathogenesis of inflammatory bowel disease (IBD) has been increasingly highlighted in recent studies. It's been reported that signal transducer and activator of transcription 3 (STAT3) O-GlcNAcylation can affect the activity of the Janus kinase2 (JAK2)/STAT3 pathway.Our recent study showed that resveratrol repairsIBDin
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Role of noradrenergic and dopaminergic systems in the antinociceptive effect of N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide in mice Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-02 Kauane Nayara Bahr Ledebuhr, Gustavo D'Avila Nunes, Marcelo Heinemann Presa, Cleidi Maria Hartmann, Benhur Godoi, Cristiani Folharini Bortolatto, César Augusto Brüning
Pain has a negative impact on public health, reducing quality of life. Unfortunately, current treatments are not fully effective and have adverse effects. Therefore, there is a need to develop new analgesic compounds. Due to promising results regarding the antinociceptive effect of N-(3-(phenylselanyl)prop-2-in-1-yl)benzamide (SePB), this study aimed to evaluate the participation of the dopaminergic
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Predicting the in vivo developmental toxicity of fenarimol from in vitro toxicity data using PBTK modelling-facilitated reverse dosimetry approach Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-01 Manisha Bhateria, Isha Taneja, Kajal Karsauliya, Ashish Kumar Sonker, Yukihiro Shibata, Hiromi Sato, Sheelendra Pratap Singh, Akihiro Hisaka
methods are widely used in modern toxicological testing; however, the data cannot be directly employed for risk assessment. toxicity of chemicals can be predicted from data using physiologically based toxicokinetic (PBTK) modelling-facilitated reverse dosimetry (PBTK-RD). In this study, a minimal-PBTK model was constructed to predict the kinetic profile of fenarimol (FNL) in rats and humans. The model
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Discovery of anticancer function of Febrifugine: Inhibition of cell proliferation, induction of apoptosis and suppression steroid synthesis in bladder cancer cells Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-01 Jingyuan Chen, Shuhao Fan, Jianhua Guo, Jian Yang, Le Pan, Yong Xia
Bladder cancer is a prevalent malignancy affecting the urinary system, which presents a significant global health concern. Although there are many treatments for bladder cancer, identifying more effective drugs and methods remains an urgent problem. As a pivotal component of contemporary medical practice, traditional Chinese medicine (TCM) assumes a crucial role in the realm of anti-tumor therapy,
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Aspongopus chinensis ach-miR-276a-3p induces breast cancer cell cycle arrest by targeting APPL2 to regulate the CDK2-Rb-E2F1 signaling pathway Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-03-01 Renlian Cai, Samiullah Khan, Xumei Chen, Haiyin Li, Jun Tan, Ying Tian, Shuai Zhao, Zhiyong Yin, Tongxian Liu, Daochao Jin, Jianjun Guo
Breast cancer, the most common cancer, presents a significant challenge to the health and longevity of women. Dallas is an insect with known anti-breast cancer properties. However, the anti-breast cancer effects and underlying mechanisms have not been elucidated. Exogenous microRNAs (miRNAs), which are derived from plants and animals, have been revealed to have notable capacities for controlling the
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Tetramethylpyrazine inhibits the inflammatory response by downregulating the TNFR1/IκB-α/NF-κB p65 pathway after spinal cord injury Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-29 Gang Liu, Luyao Huo, Bowen Deng, Shengyuan Jiang, Yi Zhao, Yanjun Mo, Huizhong Bai, Lin Xu, Chuanyu Hu, Xiaohong Mu
Previous studies have demonstrated that tetramethylpyrazine (TMP) can enhance the recovery of motor function in spinal cord injury (SCI) rats. However, the underlying mechanism involved in this therapeutic effect remains to be elucidated. We conducted RNA sequencing with a network pharmacology strategy to predict the targets and mechanism of TMP for SCI. The modified Allen's weight-drop method was
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Elucidating the distinctive regulatory effects and mechanisms of active compounds in Salvia miltiorrhiza Bunge via network pharmacology: Unveiling their roles in the modulation of platelet activation and thrombus formation Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-28 Ying Zhang, Guang Xin, Qilong Zhou, Xiuxian Yu, Lijuan Feng, Ao Wen, Kun Zhang, Tingyu Wen, Xiaoli Zhou, Qiuling Wu, Hongchen He, Wen Huang
Bunge. (DS), as an important traditional Chinese medicine (TCM), has a long history of usage for promoting blood circulation and removing blood stasis. Modern studies have shown that the chemical components of DS have many biological activities such as cardiovascular protection, anti-arrhythmia, anti-atherosclerosis, improvement of microcirculation, protection of myocardium, inhibition and removal
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Bioactive C-phycocyanin exerts immunomodulatory and antitumor activity in mice with induced melanoma Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-28 Mariana Teixeira Santos Figueiredo Salgado, Mayara Cristini Sebastião Silva, Camilly Fratelli, Anna Rafaela Cavalcante Braga, Thacyana Beatriz Guimarães Lopes, Enio Ferreira, Istefani Luciene Dayse da Silva, Luciana Souza de Paiva, Ana Paula de Souza Votto
Melanoma is the most aggressive and deadly skin cancer. The difficulty in its treatment arises from its ability to suppress the immune system, making it crucial to find a substance that increases anti-tumor immunity. C-phycocyanin C-PC) appears as a promising bioactive, with multifaceted effects against several cancers, but its efficacy against melanoma has only been tested . Therefore, we investigated
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Maternal exposure to glyphosate-based herbicide causes vascular dysfunction in offspring female rats Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-27 Jeniffer Ailane Nunes Torres, Dayenne Cintia Alves de Lima, Vivian Giselly da Silva Moraes, Marcos Veríssimo de Oliveira Cardoso, Luciano Augusto de Araújo Ribeiro, Fabrício Souza Silva, Diego Barbosa de Queiroz
This study analyzed how glyphosate exposure in the gestational period affects vascular function in their female offspring and whether oxidative stress is involved in this effect. To this, pregnant Wistar rats were exposed through drinking water to 0.2% of a glyphosate commercial formulation, and we analyzed the response to acetylcholine and phenylephrine in the aorta from offspring of Glyphosate-based
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Efficacy of a combined anti-seizure treatment against cholinergic established status epilepticus following a sarin nerve agent insult in rats Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-21 Shlomi Lazar, Adi Neufeld-Cohen, Inbal Egoz, Shlomi Baranes, Rellie Gez, Pnina Glick, Maayan Cohen, Hila Gutman, Shira Chapman, Ariel Gore
The development of refractory status epilepticus (SE) following sarin intoxication presents a therapeutic challenge. Here, we evaluated the efficacy of delayed combined double or triple treatment in reducing abnormal epileptiform seizure activity (ESA) and the ensuing long-term neuronal insult. SE was induced in rats by exposure to 1.2 LD sarin followed by treatment with atropine and TMB4 (TA) 1 min
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Branching morphogenesis of the mouse mammary gland after exposure to benzophenone-3 Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-20 Gonzalo Schierano-Marotti, Gabriela A. Altamirano, Sofia Oddi, Ayelen L. Gomez, Nicole Meyer, Mónica Muñoz-de-Toro, Ana C. Zenclussen, Horacio A. Rodríguez, Laura Kass
Pubertal mammary branching morphogenesis is a hormone-regulated process susceptible to exposure to chemicals with endocrine disruptive capacity, such as the UV-filter benzophenone-3 (BP3). Our aim was to assess whether intrauterine or exposure to BP3 modified the branching morphogenesis of the female mouse mammary gland. For this, pregnant mice were dermally exposed to BP3 (0.15 or 50 mg/kg/day) from
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Fenpropathrin provoked kidney damage via controlling the NLRP3/Caspase-1/GSDMD–mediated pyroptosis: The palliative role of curcumin-loaded chitosan nanoparticles Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-19 Yasmina M. Abd-Elhakim, Amany Abdel-Rahman Mohamed, Ahmed E. Noreldin, Tarek Khamis, Areej A. Eskandrani, Ghalia Shamlan, Wafa S. Alansari, Badriyah S. Alotaibi, Manal E. Alosaimi, Mohammed Ageeli Hakami, Samah S. Abuzahrah
This study assessed the ability of formulated curcumin-loaded chitosan nanoparticles (CU-CS-NPs) to reduce the kidney damage resulting from fenpropathrin (FPN) in rats compared to curcumin (CU) in rats. Sixty male Sprague Dawley rats were separated into six groups and orally administered 1 mL/kg b.wt corn oil, 50 mg CU/kg b.wt, 50 mg CU-CS-NPs /kg b.wt., 15 mg FPN /kg b.wt, CU+ FPN or CU-CS-NPs + FPN
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Can exposure to lisdexamfetamine dimesylate from juvenile period to peripubertal compromise male reproductive parameters in adult rats? Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-18 Julia Stein, Bárbara Campos Jorge, Lívia Trippe Nagaoka, Ana Carolina Casali Reis, Beatriz de Matos Manoel, Alana Rezende Godoi, Vanessa Caroline Fioravante, Francisco Eduardo Martinez, Patrícia Fernanda Felipe Pinheiro, André Sampaio Pupo, Arielle Cristina Arena
Lisdexamfetamine (LDX) is a d-amphetamine prodrug used to treat attention deficit and hyperactivity disorder, a common neurodevelopmental disorder in children and adolescents. Due to its action mediated by elevated levels of catecholamines, mainly dopamine and noradrenaline, which influence hormonal regulation and directly affect the gonads, this drug may potentially disrupt reproductive performance
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Chronic arsenic exposure induces malignant transformation of human HaCaT cells through both deterministic and stochastic changes in transcriptome expression Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-17 Mayukh Banerjee, Sudhir Srivastava, Shesh N. Rai, J. Christopher States
Biological processes are inherently stochastic, i.e., are partially driven by hard to predict random probabilistic processes. Carcinogenesis is driven both by stochastic and deterministic (predictable non-random) changes. However, very few studies systematically examine the contribution of stochastic events leading to cancer development In differential gene expression studies, the established data
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Foretinib, a c-MET receptor tyrosine kinase inhibitor, tackles multidrug resistance in cancer cells by inhibiting ABCB1 and ABCG2 transporters Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-15 Somayeh Nazari, Fatemeh Mosaffa, Alireza Poustforoosh, Motahareh Mortazavi, Luciano Saso, Omidreza Firuzi, Fatemeh Moosavi
ABC transporter-mediated multidrug resistance (MDR) remains a major obstacle for cancer pharmacological treatment. Some tyrosine kinase inhibitors (TKIs) have been shown to reverse MDR. The present study was designed to evaluate for the first time whether foretinib, a multitargeted TKI, can circumvent ABCB1 and ABCG2-mediated MDR in treatment-resistant cancer models. Accumulation of fluorescent substrates
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Quercetin alleviates the toxicity of difenoconazole to the respiratory system of carp by reducing ROS accumulation and maintaining mitochondrial dynamic balance Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-10 Xiaomeng Ji, Jiajia Guo, Yeyun Ma, Shuai Zhang, Zuwang Yang, Yuanyuan Li, Kaixin Ping, Yue Xin, Zibo Dong
Difenoconazole (DFZ) is a fungicidal pesticide extensively employed for the management of fungal diseases in fruits, vegetables, and cereal crops. However, its potential environmental impact cannot be ignored, as DFZ accumulation is able to lead to aquatic environment pollution and harm to non-target organisms. Quercetin (QUE), a flavonoid abundant in fruits and vegetables, possesses antioxidant and
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Arsenic exposure is associated with alterations to multiple red blood cell parameters among adults in rural Bangladesh Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-09 Sebastian Medina, Qian-Yun Zhang, Fredine T. Lauer, Laura V. Santos-Medina, Pam Factor-Litvak, Tariqul Islam, Mahbubul Eunus, Mizanour Rahman, Mohammad Nasir Uddin, Ke Jian Liu, Faruque Parvez
Chronic arsenic exposures are associated with multiple hematologic disturbances, including anemia. The goal of this study was to evaluate associations between arsenic exposures and hematological parameters among men and women who are chronically exposed to elevated levels of arsenic from drinking water. Hematologic analyses were performed on blood collected from 755 participants (45% male and 54% female)
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Minocycline attenuates the bilirubin-induced developmental neurotoxicity through the regulation of innate immunity and oxidative stress in zebrafish embryos Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-09 Guanghua Xiong, Tianle Hu, Yihong Yang, Haiyan Zhang, Meiling Han, Jiahao Wang, Yipeng Jing, Hongbo Liu, Xinjun Liao, Yong Liu
When liver or intestinal function is impaired, bilirubin accumulates in the body and leads to neonatal jaundice. However, the potential negative effects caused by excessive accumulation of bilirubin such as developmental immunotoxicity and neurotoxicity remain unclear. We used a zebrafish model to establish bilirubin-induced jaundice symptoms and evaluated the toxic effects of bilirubin in aquatic
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Suppression of neutrophil extracellular traps is responsible for the amelioration of chemotherapeutic intestinal injury by the natural compound PEITC Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-08 Mei Bai, Shuaifei Li, Cui Zhang, Ning An, Jie Wang, Jia Qin, Rumeng Jia, Wentao Liu, Jingcai Cheng, Xuefeng Wu, Qiang Xu
Intestinal injury is one of the most debilitating side effects of many chemotherapeutic agents, such as irinotecan hydrochloride (CPT-11). Accumulating evidence indicates that neutrophil extracellular traps (NETs) play a critical role in the symptoms of ischemia and inflammation related to chemotherapy. The present study investigated the effects and possible mechanisms of phenethyl isothiocyanate (PEITC)
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Elucidating the relationship between metabolites and breast cancer: A Mendelian randomization study Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-08 Yilong Lin, Yue Zhang, Songsong Wang, Qingmo Yang
The evidence about the causal roles of metabolites in breast cancer is lacking. This study conducted a systematic evaluation of the potential causal relationship between 1091 human blood metabolites, 309 metabolite ratios, and the likelihood of developing breast cancer and its subtype by employing a two-sample bidirectional Mendelian randomization (MR) approach Four metabolites, including tryptophan
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Quantification of the tissue distribution and accumulation of the neonicotinoid pesticide clothianidin and its metabolites in maternal and fetal mice Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-07 Tetsushi Hirano, Shuji Ohno, Yoshinori Ikenaka, Kanoko Onaru, Shizuka Kubo, Yuka Miyata, Mizuki Maeda, Youhei Mantani, Toshifumi Yokoyama, Collins Nimako, Yared Beyene Yohannes, Shouta M.M. Nakayama, Mayumi Ishizuka, Nobuhiko Hoshi
Neonicotinoids (NNs) are commonly used pesticides that have a selective agonistic action on insect nicotinic acetylcholine receptors. Recent evidence has shown that NNs have adverse effects in the next generation of mammals, but it remains unclear how NNs transferred from dams to fetuses are distributed and accumulated in fetal tissues. Here, we aimed to clarify the tissue distribution and accumulation
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Anti-inflammatory effects of cannabidiol in early stages of neuroinflammation induced by high-fat diet in cerebral cortex of rats Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-07 Aleksandra Opęchowska, Kacper Karpiuk, Andrii Zahorodnii, Ewa Harasim-Symbor, Adrian Chabowski, Karolina Konstantynowicz-Nowicka
High-fat diet (HFD) contributes to neuroinflammation forming, hence it is crucial to find safe and effective substances that are able to counteract its progress. The anti-inflammatory properties of phytocannabinoids acquired from the plant have been widely acknowledged. We evaluated the effects of cannabidiol (CBD) treatment on induced by applying HFD early stages of neuroinflammation in Wistar rat
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Therapeutic potential and mechanisms of Rifaximin in ameliorating iron overload-induced ferroptosis and liver fibrosis in vivo and in vitro Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-06 Qi Yuan, Yuan Fang, Jingyun Guo, Zheng Zhang, Jinmao Liao, Jia Kuang
Liver fibrosis could progress to liver cirrhosis with several contributing factors, one being iron overload which triggers ferroptosis, a form of regulated cell death. Rifaximin, a non-absorbable antibiotic, has shown promise in mitigating fibrosis, primarily by modulating gut microbiota. This study investigated the effects and mechanisms of rifaximin on iron overload-related hepatic fibrosis and ferroptosis
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In vitro assessment of potential endocrine disrupting activities of chlorinated paraffins of various chain lengths Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-06 Mikala Melchiors, Kieu-mi Tran, Terje Svingen, Anna Kjerstine Rosenmai
The production of chlorinated paraffins (CPs) has risen in the past two decades due to their versatile industrial applications. Consequently, CPs are now widely detected in human food sources, the environment, and in human matrices such as serum, the placenta and breast milk. This raises concern about prenatal and postnatal exposure. While some studies suggest that certain short-chained CPs (SCCPs)
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Paeoniflorin alleviated muscle atrophy in cancer cachexia through inhibiting TLR4/NF-κB signaling and activating AKT/mTOR signaling Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-06 Zixia Zhu, Cong Li, Xiaofan Gu, Xiaoting Wang, Gang Zhang, Meng Fan, Yun Zhao, Xuan Liu, Xiongwen Zhang
Cancer cachexia is a progressive wasting syndrome, which is mainly characterized by systemic inflammatory response, weight loss, muscle atrophy, and fat loss. Paeoniflorin (Pae) is a natural compound extracted from the dried root of Pallas, which is featured in anti-inflammatory, antioxidant, and immunoregulatory pharmacological activities. While, the effects of Pae on cancer cachexia had not been
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Exposure of human glioblastoma cells to thimerosal inhibits the thioredoxin system and decreases tumor growth-related factors Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-05 Isabella Bramatti, Michael Aschner, Vasco Branco, Cristina Carvalho
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Effect of plasma exosome lncRNA on isoproterenol hydrochloride-induced cardiotoxicity in rats Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-02 Liyuan Zhao, Lei Shi, Zixuan Yang, Minhui Zheng, Zhimin Sun, Luyao Sun, Mengyun Gu, Xin Song, Gang Liu, Feng Miao, Ming Wang, Shaoqiu Zheng, Peng Zhang, Naping Tang, Kelan Liu
Isoprenaline hydrochloride (IH) is a β-adrenergic receptor agonist commonly used in the treatment of hypotension, shock, asthma, and other diseases. However, IH-induced cardiotoxicity limits its application. A large number of studies have shown that long noncoding RNA (lncRNA) regulates the occurrence and development of cardiovascular diseases. This study aimed to investigate whether abnormal lncRNA
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Overexpression of Nrf2 reverses ferroptosis induced by Arenobufagin in gastric cancer Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-02-01 Jiao Long, Wenjun Wang, Jing Chu, Yueyue Li, Meng Wang, Jingjing Su, Yuting Yang, GuoKai Wang, Qinglin Li, Hui Cheng
Arenobufagin (ArBu) is a natural monomer extracted and isolated from the secretion of the Chinese toad, also known as toad venom. This compound exerts anti-tumor effects by promoting apoptosis in tumor cells, inhibiting tumor angiogenesis, and preventing the invasion and migration of tumor cells. However, their impact on ferroptosis in tumor cells has yet to be fully confirmed. In this study, we established
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GAS5 promotes cytarabine induced myelosuppression via inhibition of hematopoietic stem cell differentiation Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-28 Yin-Xiao Du, Jing Yang, Han Yan, Yan-Ling Liu, Xiao-Ping Chen
Cytarabine (Ara-C) is widely used in the induction chemotherapy for acute myeloid leukemia (AML). Association between LncRNA GAS5 genetic polymorphism and the recovery of hematopoietic function after Ara-C-based chemotherapy is observed. This study aimed to identify whether intervention of GAS5 expression and GAS5 genotype affect Ara-C-induced inhibition of hematopoietic stem cells (HSCs) differentiation
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Tanshinone IIA modulates cancer cell morphology and movement via Rho GTPases-mediated actin cytoskeleton remodeling Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-28 En-yu Liang, Meng-he Huang, Ying-ting Chen, Peng-wei Zhang, Yan Shen, Xiao-xin Tu, Wei-ye Chen, Yi Wang, Jun Yan, Hong-yu Wang, Pei-feng Ke, Xian-zhang Huang
Actin filaments form unique structures with robust actin bundles and cytoskeletal networks affixed to the extracellular matrix and interact with neighboring cells, which are crucial structures for cancer cells to acquire a motile phenotype. This study aims to investigate a novel antitumor mechanism by which Tanshinone IIA (Tan IIA) modulates the morphology and migration of liver cancer cells via actin
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Levocabastine ameliorates cyclophosphamide-induced cardiotoxicity in Swiss albino mice: Targeting TLR4/NF-κB/NLRP3 signaling pathway Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-24 Wasim Akram, Abul Kalam Najmi, M. Mumtaz Alam, Syed Ehtaishamul Haque
Cyclophosphamide (CP), although a potent anti-cancer drug, causes cardiotoxicity as a side effect that limits its use. Hence, a specific medicine that can lower cardiotoxicity and be utilised as an adjuvant in cancer treatment is very much needed. In this light, we intended to assess the protective potential of levocabastine (LEV) on CP-induced cardiotoxicity in Swiss albino mice. Mice were administered
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Nonclinical pharmacokinetics, pharmacodynamics and safety assessment of a FLT3L-Fc molecule for cancer immunotherapy Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-24 Kai Connie Wu, Adeyemi O. Adedeji, Tanja S. Zabka, Iraj Hosseini, Radhika Kenkre, Jennifer A. Getz, Tien Nguyen, Jérémie Decalf, Travis W. Bainbridge, Jennifer A. Chilton, Christine C. Moussion, Gautham K. Rao
FLT3L-Fc is a cytokine-Fc fusion agonizing receptor-type tyrosine-protein kinase FLT3 (fms-related tyrosine kinase 3; CD135). FLT3 is expressed on dendritic cells (DCs) as well as myeloid and lymphoid progenitors. Nonclinical pharmacokinetics, pharmacodynamics and safety of FLT3L-Fc were investigated in rats and cynomolgus monkeys. FLT3L-Fc induced robust pharmacodynamic responses, evidenced by marked
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Methionine redox regulation of actin-interacting proteins primarily governs antioxidative signaling and response to the salvianolic acid B treatment in EA.hy926 cells Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-23 Ai-Cheng Wang, Xiao-Ming Qi, Qing-Fang Li, Yi-Jia Feng, Yuan-Lin Zhang, Hui-Zhi Wei, Jin-Shan Li, Yuan-Biao Qiao, Qing-Shan Li
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Prenatal arsenite exposure alters maternal cardiac remodeling during late pregnancy Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-23 Nicole Taube, Raihan Kabir, Obialunanma V. Ebenebe, Haley Garbus, Sarah-Marie Alam El Din, Emily Illingworth, Michael Fitch, Nadan Wang, Mark J. Kohr
Exposure to inorganic arsenic through drinking water is widespread and has been linked to many chronic diseases, including cardiovascular disease. Arsenic exposure has been shown to alter hypertrophic signaling in the adult heart, as well as in utero offspring development. However, the effect of arsenic on maternal cardiac remodeling during pregnancy has not been studied. As such, there is a need to
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Dexamethasone targets actin cytoskeleton signaling and inflammatory mediators to reverse sulfur mustard-induced toxicity in rabbit corneas Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-23 Rama Kant, Neha Mishra, Kushal Kandhari, Laura Saba, Cole Michel, Richard Reisdorph, Neera Tewari-Singh, Mina B. Pantcheva, J. Mark Petrash, Chapla Agarwal, Rajesh Agarwal
Purpose Sulfur mustard (SM), a bi-functional alkylating agent, was used during World War I and the Iran-Iraq war. SM toxicity is ten times higher in eyes than in other tissues. Cornea is exceptionally susceptible to SM-injuries due to its anterior positioning and mucous-aqueous interphase. Ocular SM exposure induces blepharitis, photosensitivity, dry eye, epithelial defects, limbal ischemia and stem
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The skin photoprotective effect of trilinolein: Induction of cellular autophagy via the AMPK-mTOR signaling pathway Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-23 Xianghong Lin, Na Deng, Huijuan Li, Jingxian Duan, Wenqiu Chen, Tao Liu, Sujiao Sun, Jimin Chu
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HIF-PHD inhibitor desidustat ameliorates iron deficiency anemia Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-22 Vishal J. Patel, Amit Joharapurkar, Samadhan G. Kshirsagar, Maulik S. Patel, Hardikkumar H. Savsani, Harshad S. Dodiya, Milan H. Rakhasiya, Chetan Kajavadara, Darshan Valani, Mukul R. Jain
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Physical activity can reduce the risk of blood cadmium and blood lead on stroke: Evidence from NHANES Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-22 Xiaoqi Deng, Dichuan Liu, Miao Li, Jie He, Yufan Fu
The detrimental impact of heavy metals on cardiovascular well-being is a global concern, and engaging in suitable physical activity has been shown to confer cardiovascular advantage. Nevertheless, the potential of exercise to mitigate the deleterious effects of heavy metals on stroke remains uncertain. We conducted a cross-sectional survey to assess the influence of blood cadmium and blood lead on
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Anti-NOTCH1 therapy with OMP-52 M51 inhibits salivary adenoid cystic carcinoma by depressing epithelial-mesenchymal transition (EMT) process and inducing ferroptosis Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-20 Ran Li, Zelong Hu, Quanxin Qiao, Die Zhou, Minglei Sun
Salivary adenoid cystic carcinoma (ACC) is a common type of salivary gland cancer, and the mechanisms underlying its progression still remain poorly understood without efficient therapies. NOTCH1, an evolutionally conserved cell-cell signaling pathway, is involved in the progression of ACC. In our study, we attempted to explore whether NOTCH1 suppression using the monoclonal anti-NOTCH1 antibody OMP-52 M51
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Corrigendum to “D-saccharic acid 1,4-lactone protects diabetic rat kidney by ameliorating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via NF-κB and PKC signaling” [Toxicology and Applied Pharmacology, 267 (2013) 16–29] Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-18 Semantee Bhattacharya, Prasenjit Manna, Ratan Gachhui, Parames C. Sil
Abstract not available
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Aucubin provides protection against cerebral ischaemia-reperfusion injury by suppressing neuronal apoptosis, oxidative stress, and inflammation through the modulation of the AKT-GSK-3β-Nrf2 signal cascade Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-20 Fang Yang, Qiufang Lian, Xin Zhang, Feng Sun, Shuaiyun Jia, Wei Zhao
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Maternal quercetin supplementation improved lipopolysaccharide-induced cognitive deficits and inflammatory response in a rat model of maternal immune activation Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-20 Hossein Abbasi, Sina Ghavami-kia, Nahid Davoodian, Najmeh Davoodian
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Baicalin − 2- ethoxyethyl ester alleviates renal fibrosis by inhibiting PI3K/AKT/NF-κB signaling pathway Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-19 Jiacun Li, Ke Zhang, Mei Xu, Huanyue Cui, Yaping Guo, Dahong Yao, Wenhua Chen, Huaimin Liang, Hangyu Wang, Jinhui Wang
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Long-term exposure to the mixture of phthalates induced male reproductive toxicity in rats and the alleviative effects of quercetin Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-11 Li-Lan Liu, Jun-Zhe Yue, Zhen-Yu Lu, Ru-Ya Deng, Can-Can Li, Ye-Na Yu, Wen-Jin Zhou, Min Lin, Hai-Tao Gao, Jiaming Liu, Ling-Zi Xia
Phthalates (PEs), such as di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) could cause reproductive and developmental toxicities, while human beings are increasingly exposed to them at low-doses. Phytochemical quercetin (Que) is a flavonoid that has estrogenic effect, anti-inflammatory and anti-oxidant effects. This study was conducted to assess the alleviative
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d-Tetramethrin causes zebrafish hepatotoxicity by inducing oxidative stress and inhibiting cell proliferation Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-11 Yang Li, Mijia Li, Shiyi Duan, Sijie Zhang, Huiqiang Lu, Xinchun Guo, Keyuan Zhong
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Spindle and kinetochore-related complex subunit 3 has a protumour function in osteosarcoma by activating the Notch pathway Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-14 Gaofeng Liang, Chaopeng Duan, June He, Liang Shi
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Esketamine induces apoptosis of nasopharyngeal carcinoma cells through the PERK/CHOP pathway Toxicol. Appl. Pharmacol. (IF 3.8) Pub Date : 2024-01-12 Yuling Cao, Huiting Li, Yunfei Gao, Jiao Long, Lei Zheng, Qi Zhang, Ningning Li, Xinjin Chi