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Source: Toxicology and Applied Pharmacology

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Total 118 results found since Jan 2013.

Characterization of acquired paclitaxel resistance of breast cancer cells and involvement of ABC transporters.
Abstract Development of taxane resistance has become clinically very important issue. The molecular mechanisms underlying the resistance are still unclear. To address this issue, we established paclitaxel-resistant sublines of the SK-BR-3 and MCF-7 breast cancer cell lines that are capable of long-term proliferation in 100nM and 300nM paclitaxel, respectively. Application of these concentrations leads to cell death in the original counterpart cells. Both sublines are cross-resistant to doxorubicin, indicating the presence of the MDR phenotype. Interestingly, resistance in both paclitaxel-resistant sublines is circ...
Source: Toxicology and Applied Pharmacology - September 20, 2016 Category: Toxicology Authors: Němcová-Fürstová V, Kopperová D, Balušíková K, Ehrlichová M, Brynychová V, Václavíková R, Daniel P, Souček P, Kovář J Tags: Toxicol Appl Pharmacol Source Type: research

Omeprazole induces heme oxygenase-1 in fetal human pulmonary microvascular endothelial cells via hydrogen peroxide-independent Nrf2 signaling pathway.
In conclusion, we provide evidence that OM transcriptionally induces HO-1 via AhR - and H2O2 - independent, but Nrf2 - dependent mechanisms. These results have important implications for human disorders where Nrf2 and HO-1 play a beneficial role. PMID: 27725188 [PubMed - as supplied by publisher]
Source: Toxicology and Applied Pharmacology - October 6, 2016 Category: Toxicology Authors: Patel A, Zhang S, Shrestha AK, Maturu P, Moorthy B, Shivanna B Tags: Toxicol Appl Pharmacol Source Type: research

SIRT1 protects cardiac cells against apoptosis induced by zearalenone or its metabolites α- and β-zearalenol through an autophagy-dependent pathway.
Abstract Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. The major ZEN metabolites are α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL). In the present study, we investigated the underlying mechanism of the toxicity induced by ZEN, α-ZOL and β-ZOL in cardiac cells (H9c2). We show that treatment with ZEN or its metabolites induces the activation of the mitochondrial pathway of apoptosis as characterized by an increase in ROS generation, a loss of mitochondrial transmembrane potential (ΔΨm) and an activation of caspases. Bes...
Source: Toxicology and Applied Pharmacology - November 22, 2016 Category: Toxicology Authors: Salem IB, Boussabbeh M, Da Silva JP, Guilbert A, Bacha H, Abid-Essefi S, Lemaire C Tags: Toxicol Appl Pharmacol Source Type: research

Methylation of Septin9 Mediated by DNMT3a Enhances Hepatic Stellate Cells Activation and Liver Fibrogenesis.
Abstract Liver fibrosis, resulting from chronic and persistent injury to the liver, is a worldwide health problem. Advanced liver fibrosis results in cirrhosis, liver failure and even hepatocellular cancer (HCC), often eventually requiring liver transplantation, poses a huge health burden on the global community. However, the specific pathogenesis of liver fibrosis remains not fully understood. Numerous basic and clinical studies have provided evidence that epigenetic modifications, especially DNA methylation, might contribute to the activation of hepatic stellate cells (HSCs), the pivotal cell type responsible fo...
Source: Toxicology and Applied Pharmacology - December 5, 2016 Category: Toxicology Authors: Wu Y, Bu F, Yu H, Li W, Huang C, Meng X, Zhang L, Ma T, Li J Tags: Toxicol Appl Pharmacol Source Type: research

Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner.
This study was aimed to explore the impact of DHA on ALD and further elaborate the underlying mechanisms. Gain- or loss-of-function analyses of FXR were applied in both in vivo and in vitro studies. Results demonstrated that DHA rescued FXR expression and activity in alcoholic rat livers. DHA also reduced serodiagnostic markers of liver injury, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase. DHA improved alcohol-induced liver histological lesions, expression of inflammation genes, and inflammatory cell infiltration. In addition, DHA not only attenuated hyperl...
Source: Toxicology and Applied Pharmacology - December 5, 2016 Category: Toxicology Authors: Xu W, Lu C, Yao L, Zhang F, Shao J, Zheng S Tags: Toxicol Appl Pharmacol Source Type: research

Autophagy contributes to 4-Amino-2-Trifluoromethyl-Phenyl Retinate-induced differentiation in human acute promyelocytic leukemia NB4 cells.
Abstract As a classic differentiation agent, all-trans retinoic acid (ATRA) has been widely used in treatment of acute promyelocytic leukemia (APL). However, clinical application of ATRA has limitations. Our previous studies suggested that 4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, could induce differentiation of APL cells in vivo and in vitro. To explore the underlying mechanism of ATPR, the effect of ATPR on autophagy of APL cells was observed in the present study. The results showed that the differentiation effect of ...
Source: Toxicology and Applied Pharmacology - January 23, 2017 Category: Toxicology Authors: Li Y, Li G, Wang K, Xie YY, Zhou RP, Meng Y, Ding R, Ge JF, Chen FH Tags: Toxicol Appl Pharmacol Source Type: research

Glycyrrhetinic acid attenuates lipopolysaccharide-induced fulminant hepatic failure in d-galactosamine-sensitized mice by up-regulating expression of interleukin-1 receptor-associated kinase-M.
Abstract Glycyrrhetinic acid (GA), the main active ingredient of licorice, reportedly has anti-inflammatory and hepatoprotective properties, but its molecular mechanisms remain be elusive. In the present study, Balb/c mice were pretreated with GA (10, 30, or 100mg/kg) 1h before lipopolysaccharide (LPS)/d-galactosamine (D-GalN) administration. In other in vitro experiment, RAW264.7 macrophages were pretreated with GA before LPS exposure. The mortality, hepatic tissue histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Toll like receptor 4 (TLR4), interleukin-1 recepto...
Source: Toxicology and Applied Pharmacology - February 13, 2017 Category: Toxicology Authors: Yin X, Xia G, Zhang L, Jiang R, Kuang G, Wang B, Chen X, Wan J Tags: Toxicol Appl Pharmacol Source Type: research

The role of cPLA2 in Methylglyoxal-induced cell apoptosis of HUVECs.
This study gives an important insight into the downstream signaling mechanisms of MGO, cPLA2-NF-κB, in endothelial apoptosis. PMID: 28341536 [PubMed - as supplied by publisher]
Source: Toxicology and Applied Pharmacology - March 21, 2017 Category: Toxicology Authors: Yuan J, Zhu C, Hong Y, Sun Z, Fang X, Wu B, Li S Tags: Toxicol Appl Pharmacol Source Type: research

Valproate induced hepatic steatosis by enhanced fatty acid uptake and triglyceride synthesis.
Abstract Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation are not yet fully understood. Here we demonstrated the involvement of fatty acid uptake and lipogenesis in VPA-induced hepatic steatosis in vitro and in vivo by using quantitative real-time PCR (qRT-PCR) analysis, western blotting analysis, fatty acid uptake assays, Nile Red staining assays, a...
Source: Toxicology and Applied Pharmacology - March 30, 2017 Category: Toxicology Authors: Bai X, Hong W, Cai P, Chen Y, Xu C, Cao D, Yu W, Zhao Z, Huang M, Jin J Tags: Toxicol Appl Pharmacol Source Type: research

Impaired autophagic flux and p62-mediated EMT are involved in arsenite-induced transformation of L-02 cells.
Abstract Autophagy is a catabolic process essential for preserving cellular homeostasis, and the epithelial-to-mesenchymal transition (EMT) is involved during tissue development and cancer progression. In arsenite-treated human hepatic epithelial (L-02) cells, arsenite reduced the autophagic flux, which caused accumulation of p62, an adaptor and receptor of autophagy. Further, in arsenite-transformed L-02 cells, the levels of E-cadherin were attenuated, but the levels of vimentin, which is expressed in mesenchymal cells, and Snail, a transcription regulator of the EMT, were up-regulated. Thus, after chronic exposu...
Source: Toxicology and Applied Pharmacology - September 6, 2017 Category: Toxicology Authors: Liu X, Ling M, Chen C, Luo F, Yang P, Wang D, Chen X, Xu H, Xue J, Yang Q, Lu L, Lu J, Bian Q, Zhang A, Liu Q Tags: Toxicol Appl Pharmacol Source Type: research

H2S protects lipopolysaccharide-induced inflammation by blocking NF κB transactivation in endothelial cells.
H2S protects lipopolysaccharide-induced inflammation by blocking NFκB transactivation in endothelial cells. Toxicol Appl Pharmacol. 2017 Nov 08;: Authors: Bourque C, Zhang Y, Fu M, Racine M, Greasley A, Pei Y, Wu L, Wang R, Yang G Abstract Hydrogen sulfide (H2S) is a novel gasotransmitter and acts as a multifunctional regulator in various cellular functions. Past studies have demonstrated a significant role of H2S and its generating enzyme cystathionine gamma-lyase (CSE) in the cardiovascular system. Lipopolysaccharide (LPS), a major pathogenic factor, is known to initiate the inflammatory immune res...
Source: Toxicology and Applied Pharmacology - November 8, 2017 Category: Toxicology Authors: Bourque C, Zhang Y, Fu M, Racine M, Greasley A, Pei Y, Wu L, Wang R, Yang G Tags: Toxicol Appl Pharmacol Source Type: research

Ghrelin protects against depleted uranium-induced bone damage by increasing osteoprotegerin/RANKL ratio.
Abstract Depleted uranium (DU) is widely used in military and civil activities, and bone is the main target organ of chronic DU toxicity. The aim of this study was to evaluate the effects of ghrelin on rats implanted with DU and explore the underlying mechanisms. The results showed that ghrelin could increase the expression of ghrelin receptor in bone tissue, thus alleviate the apoptosis of bone tissue after 3 months of 0.3 g DU embedded in the tibia. Micro-computed tomography examination showed that after DU implantation, the density of cortical bone showed no significant difference, but the trabecular bone d...
Source: Toxicology and Applied Pharmacology - February 22, 2018 Category: Toxicology Authors: Hao Y, Gao R, Lu B, Ran Y, Yang Z, Liu J, Li R Tags: Toxicol Appl Pharmacol Source Type: research

nAChRs-ERK1/2-Egr-1 signaling participates in the developmental toxicity of nicotine by epigenetically down-regulating placental 11 β-HSD2.
This study aimed to elucidate the epigenetically regulatory mechanism of nicotine on placental 11β-HSD2 expression. Pregnant Wistar rats were administered 1.0 mg/kg nicotine subcutaneously twice a day from gestational day 9 to 20. The results showed that prenatal nicotine exposure increased corticosterone levels in the placenta and fetal serum, disrupted placental morphology and endocrine function, and reduced fetal bodyweight. Meanwhile, histone modification abnormalities (decreased acetylation and increased di-methylation of histone 3 Lysine 9) on the HSD11B2 promoter and lower-expression of 11β-HSD2 were observed. F...
Source: Toxicology and Applied Pharmacology - February 24, 2018 Category: Toxicology Authors: Zhou J, Liu F, Yu L, Xu D, Li B, Zhang G, Huang W, Li L, Zhang Y, Zhang W, Wang H Tags: Toxicol Appl Pharmacol Source Type: research

Yangonin protects against cholestasis and hepatotoxity via activation of farnesoid X receptor in vivo and in vitro.
Abstract Cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Recently obeticholic acid (OCA) which is a farnesoid X receptor (FXR) agonist was approved by FDA to treat cholestatic liver diseases, which provided us a newly therapeutic strategy against cholestasis. The purpose of the current study is to screen novel FXR agonists and verify the anti-cholestasis effect of yangonin in vivo and in vitro. The computational strategy of two-dimensional virtual screening was used to search for new FXR agonists, and dual-luci...
Source: Toxicology and Applied Pharmacology - April 13, 2018 Category: Toxicology Authors: Gao X, Fu T, Wang C, Ning C, Liu K, Liu Z, Sun H, Ma X, Huo X, Yang X, Zou M, Meng Q Tags: Toxicol Appl Pharmacol Source Type: research

Crystalline silica alters Sulfatase-1 expression in rat lungs which influences hyper-proliferative and fibrogenic effects in human lung epithelial cells.
In this study, CS-induced down-regulation of SULF1, and increases in Sulfated-HSPGs, were determined in human BECs, and in rat lungs. By siRNA and plasmid transfection techniques the effects of SULF1 expression on silica-induced fibrogenic and proliferative gene expression were determined. These studies confirmed down-regulation of SULF1 and subsequent increases in sulfated-HSPGs in vitro. Moreover, short-term exposure of rats to CS resulted in similar changes in vivo. Conversely, effects were reversed after long term CS exposure of rats. SULF1 knockdown, and overexpression alleviated and exacerbated silica-induced decreas...
Source: Toxicology and Applied Pharmacology - April 16, 2018 Category: Toxicology Authors: Perkins TN, Peeters PM, Albrecht C, Schins RPF, Dentener MA, Mossman BT, Wouters EFM, Reynaert NL Tags: Toxicol Appl Pharmacol Source Type: research