Toxicology and Applied Pharmacology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Suppression of neutrophil extracellular traps is responsible for the amelioration of chemotherapeutic intestinal injury by the natural compound PEITC
Toxicol Appl Pharmacol. 2024 Feb 8;484:116857. doi: 10.1016/j.taap.2024.116857. Online ahead of print.ABSTRACTIntestinal 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) in inhibiting NETs and alleviating chemotherapeutic intestinal injury. CPT-11 induced robust neutrophil activati...
Source: Toxicology and Applied Pharmacology - February 10, 2024 Category: Toxicology Authors: Mei Bai Shuaifei Li Cui Zhang Ning An Jie Wang Jia Qin Rumeng Jia Wentao Liu Jingcai Cheng Xuefeng Wu Qiang Xu Source Type: research

Quantification of the tissue distribution and accumulation of the neonicotinoid pesticide clothianidin and its metabolites in maternal and fetal mice
Toxicol Appl Pharmacol. 2024 Feb 7;484:116847. doi: 10.1016/j.taap.2024.116847. Online ahead of print.ABSTRACTNeonicotinoids (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 properties of the NN clothianidin (CLO) and its 6 metabolites in 7 tissues and blood in both dams and fetuses of m...
Source: Toxicology and Applied Pharmacology - February 9, 2024 Category: Toxicology Authors: 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 Source Type: research

Anti-inflammatory effects of cannabidiol in early stages of neuroinflammation induced by high-fat diet in cerebral cortex of rats
Toxicol Appl Pharmacol. 2024 Feb 7;484:116856. doi: 10.1016/j.taap.2024.116856. Online ahead of print.ABSTRACTHigh-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 Cannabis 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 cerebral cortex. In our 7-week experiment, CBD was injected intraperitoneally over the last 14days at a dose ...
Source: Toxicology and Applied Pharmacology - February 9, 2024 Category: Toxicology Authors: Aleksandra Op ęchowska Kacper Karpiuk Andrii Zahorodnii Ewa Harasim-Symbor Adrian Chabowski Karolina Konstantynowicz-Nowicka Source Type: research

In vitro assessment of potential endocrine disrupting activities of chlorinated paraffins of various chain lengths
Toxicol Appl Pharmacol. 2024 Feb 6;484:116843. doi: 10.1016/j.taap.2024.116843. Online ahead of print.ABSTRACTThe 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) may have endocrine disrupting properties, knowledge about potential endocrine disrupting potential of medium- (MCCP) a...
Source: Toxicology and Applied Pharmacology - February 8, 2024 Category: Toxicology Authors: Mikala Melchiors Kieu-Mi Tran Terje Svingen Anna Kjerstine Rosenmai Source Type: research

Therapeutic potential and mechanisms of Rifaximin in ameliorating iron overload-induced ferroptosis and liver fibrosis in vivo and in vitro
This study investigated the effects and mechanisms of rifaximin on iron overload-related hepatic fibrosis and ferroptosis. In an iron overload-induced liver fibrosis model in mice and in ferric ammonium citrate (FAC)-stimulated primary hepatocytes, treatment with rifaximin showed significant therapeutic effects. Specifically, it ameliorated the processes of ferroptosis triggered by iron overload, reduced liver injury, and alleviated fibrosis. This was demonstrated by decreased iron accumulation in the liver, improved liver function, and reduced fibrotic area and collagen deposition. Rifaximin also modulated key proteins re...
Source: Toxicology and Applied Pharmacology - February 8, 2024 Category: Toxicology Authors: Qi Yuan Yuan Fang Jingyun Guo Zheng Zhang Jinmao Liao Jia Kuang Source Type: research

Paeoniflorin alleviated muscle atrophy in cancer cachexia through inhibiting TLR4/NF- κB signaling and activating AKT/mTOR signaling
Toxicol Appl Pharmacol. 2024 Feb 6;484:116846. doi: 10.1016/j.taap.2024.116846. Online ahead of print.ABSTRACTCancer 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 Paeonia lactiflora Pallas, which is featured in anti-inflammatory, antioxidant, and immunoregulatory pharmacological activities. While, the effects of Pae on cancer cachexia had not been reported before. In the present study, the effects of Pae on muscle atrophy in cancer cachexia were ...
Source: Toxicology and Applied Pharmacology - February 8, 2024 Category: Toxicology Authors: Zixia Zhu Cong Li Xiaofan Gu Xiaoting Wang Gang Zhang Meng Fan Yun Zhao Xuan Liu Xiongwen Zhang Source Type: research

Exposure of human glioblastoma cells to thimerosal inhibits the thioredoxin system and decreases tumor growth-related factors
The objective of this study was to verify whether thimerosal is a suitable candidate for hard repurposing to control glioblastoma; therefore, the effects of this molecule were evaluated in human GBM (U87) cells. Our novel results show that TmHg decreased cellular viability (>50%) and migration (up to 90% decrease in wound closure), reduced thioredoxin reductase (TrxR/TXNRD1) and thioredoxin (Trx) activity, and increased reactive oxygen species (ROS) generation. Moreover, TmHg reduced HIF-1α expression (35%) as observed by immunofluorescence. Co-exposure of U87 cells to TmHg and TMZ reduced HIF-1α, VEGF, and phosphoryl...
Source: Toxicology and Applied Pharmacology - February 7, 2024 Category: Toxicology Authors: Isabella Bramatti Michael Aschner Vasco Branco Cristina Carvalho Source Type: research

Overexpression of Nrf2 reverses ferroptosis induced by Arenobufagin in gastric cancer
In this study, we established a subcutaneous transplant tumor model in nude mice to investigate the inhibitory effect of ArBu on gastric cancer cells (MGC-803) and the safety of drug delivery. in vitro experiments, we screened the most sensitive cancer cell lines using the MTT method and determined the response of ArBu to cell death. Use flow cytometry to measure cytoplasmic and lipid reactive oxygen species (ROS) levels. Determine the expression levels of ferritin-related proteins through Western blot experiments. In addition, a MGC-803 cell model overexpressing Nrf2 was created using lentiviral transfection to investigat...
Source: Toxicology and Applied Pharmacology - February 2, 2024 Category: Toxicology Authors: Jiao Long Wenjun Wang Jing Chu Yueyue Li Meng Wang Jingjing Su Yuting Yang GuoKai Wang Qinglin Li Hui Cheng Source Type: research

Effect of plasma exosome lncRNA on isoproterenol hydrochloride-induced cardiotoxicity in rats
This study aimed to investigate whether abnormal lncRNA expression is involved in IH-mediated cardiotoxicity. First, the Sprague-Dawley (SD) rat myocardial injury model was established. Circulating exosomes were extracted from the plasma of rats and identified. In total, 108 differentially expressed (DE) lncRNAs and 150 DE mRNAs were identified by sequencing. These results indicate that these lncRNAs and mRNAs are substantially involved in chemical cardiotoxicity. Further signaling pathway and functional studies indicated that lncRNAs and mRNAs regulate several biological processes, such as selective mRNA splicing through ...
Source: Toxicology and Applied Pharmacology - February 2, 2024 Category: Toxicology Authors: 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 Source Type: research

Tanshinone IIA modulates cancer cell morphology and movement via Rho GTPases-mediated actin cytoskeleton remodeling
In conclusion, Tan IIA can induce dramatic actin cytoskeleton remodeling by inhibiting the protein synthesis of actin and Rho GTPases, resulting in the suppression of tumor growth and migration. Targeting the actin cytoskeleton of Tan IIA is a promising strategy for HCC treatment.PMID:38290667 | DOI:10.1016/j.taap.2024.116839 (Source: Toxicology and Applied Pharmacology)
Source: Toxicology and Applied Pharmacology - January 30, 2024 Category: Toxicology Authors: 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 Source Type: research

GAS5 promotes cytarabine induced myelosuppression via inhibition of hematopoietic stem cell differentiation
In conclusion, our study highlights that GAS5 inhibited the in vitro proliferation and reduced the hematopoietic colony-forming ability of cord blood-derived CD34+ cells, with the most pronounced effect observed on CFU-GEMM formation. GAS5 also enhanced the inhibitory effect of Ara-C on the in vitro hematopoietic ability of CD34+ HSCs.PMID:38290668 | DOI:10.1016/j.taap.2024.116841 (Source: Toxicology and Applied Pharmacology)
Source: Toxicology and Applied Pharmacology - January 30, 2024 Category: Toxicology Authors: Yin-Xiao Du Jing Yang Han Yan Yan-Ling Liu Xiao-Ping Chen Source Type: research

Nonclinical pharmacokinetics, pharmacodynamics and safety assessment of a FLT3L-Fc molecule for cancer immunotherapy
Toxicol Appl Pharmacol. 2024 Feb;483:116837. doi: 10.1016/j.taap.2024.116837. Epub 2024 Jan 24.ABSTRACTFLT3L-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 expansion of peripheral blood cDC1s, cDC2s, and pDCs (up to 301-fold in rats and 378-fold in monkeys), peaking at 8-10 day...
Source: Toxicology and Applied Pharmacology - January 26, 2024 Category: Toxicology Authors: Kai Connie Wu Adeyemi O Adedeji Tanja S Zabka Iraj Hosseini Radhika Kenkre Jennifer A Getz Tien Nguyen J érémie Decalf Travis W Bainbridge Jennifer A Chilton Christine C Moussion Gautham K Rao Source Type: research

Levocabastine ameliorates cyclophosphamide-induced cardiotoxicity in Swiss albino mice: Targeting TLR4/NF- κB/NLRP3 signaling pathway
Toxicol Appl Pharmacol. 2024 Feb;483:116838. doi: 10.1016/j.taap.2024.116838. Epub 2024 Jan 24.ABSTRACTCyclophosphamide (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 LEV (50 and 100 μg/kg, i.p.) daily for 14 days and CP at 200 mg/kg, intraperitoneally once on the 7th day. On the 15th ...
Source: Toxicology and Applied Pharmacology - January 26, 2024 Category: Toxicology Authors: Wasim Akram Abul Kalam Najmi M Mumtaz Alam Syed Ehtaishamul Haque Source Type: research

The skin photoprotective effect of trilinolein: Induction of cellular autophagy via the AMPK-mTOR signaling pathway
This study delves into the photoprotective effect of trilinolein on UVB-irradiated Human Skin Fibroblast (HSF) cells and the underlying mechanisms. Our findings reveal that trilinolein had a photoprotective effect on HSF cells: trilinolein enhanced cellular autophagy, restored UVB-inhibited cell proliferative viability, and curbing UVB-induced reactive oxygen species (ROS) and apoptosis. Intriguingly, after inhibition of TL-induced autophagy via wortmannin, diminished trilinolein's photoprotective effects. Meanwhile, trilinolein was shown to modulate the AMPK-mTOR signaling pathway, thus enhance cellular autophagy in HSF c...
Source: Toxicology and Applied Pharmacology - January 25, 2024 Category: Toxicology Authors: Xianghong Lin Na Deng Huijuan Li Jingxian Duan Wenqiu Chen Tao Liu Sujiao Sun Jimin Chu Source Type: research

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. 2024 Feb;483:116835. doi: 10.1016/j.taap.2024.116835. Epub 2024 Jan 23.ABSTRACTActin-interacting proteins are important molecules for filament assembly and cytoskeletal signaling within vascular endothelium. Disruption in their interactions causes endothelial pathogenesis through redox imbalance. Actin filament redox regulation remains largely unexplored, in the context of pharmacological treatment. This work focused on the peptidyl methionine (M) redox regulation of actin-interacting proteins, aiming at elucidating its role on governing antioxidative signaling and response. Endothelial EA.hy926 cel...
Source: Toxicology and Applied Pharmacology - January 25, 2024 Category: Toxicology Authors: 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 Source Type: research