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Source: Toxicology and Applied Pharmacology

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Total 118 results found since Jan 2013.

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

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

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

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

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

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

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

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

Hepatocyte-protective effect of nectandrin B, a nutmeg lignan, against oxidative stress: Role of Nrf2 activation through ERK phosphorylation and AMPK-dependent inhibition of GSK-3 β.
This study investigated the hepatocyte-protective effect of nectandrin B against tert-butylhydroperoxide-induced oxidative injury and the underlying molecular mechanism. The cell viability assay revealed that nectandrin B prevents apoptosis stimulated by tert-butylhydroperoxide in both HepG2 cells and primary mouse hepatocytes. Nectandrin B also attenuated ROS production and restored the depleted glutathione level. Real-time PCR and immunoblot analyses showed that the expression of glutamate-cysteine ligase, an enzyme responsible for the glutathione biosynthesis, was induced by nectandrin B, indicating its indirect antioxi...
Source: Toxicology and Applied Pharmacology - August 6, 2016 Category: Toxicology Authors: Song JS, Kim EK, Choi YW, Oh WK, Kim YM Tags: Toxicol Appl Pharmacol Source Type: research

Bifunctional Alkylating Agent-Mediated MGMT-DNA Cross-linking and its Proteolytic Cleavage in 16HBE Cells.
Abstract Nitrogen mustard (NM), a bifunctional alkylating agent (BAA), contains two alkyl arms and can act as a cross-linking bridge between DNA and protein to form a DNA-protein cross-link (DPC). O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme for alkyl adducts removal, is found to enhance cell sensitivity to BAAs and to promote damage, possibly due to its stable covalent cross-linking with DNA mediated by BAAs. To investigate MGMT-DNA cross-link (mDPC) formation and its possible dual roles in NM exposure, human bronchial epithelial cell line 16HBE was subjected to different concentrations of...
Source: Toxicology and Applied Pharmacology - June 20, 2016 Category: Toxicology Authors: Cheng J, Ye F, Dan G, Zhao Y, Wang B, Zhao J, Sai Y, Zou Z Tags: Toxicol Appl Pharmacol Source Type: research

Effect of TCDD on the fate of epithelial cells isolated from human fetal palatal shelves (hFPECs).
Abstract Cleft palate is caused by the failure of palatal midline epithelial cells to disintegrate, which is necessary for palatal mesenchymal confluence. Although 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure is linked to cleft palate at a high rate, the mechanism remains to be elucidated. The present study was designed to determine the effects of TCDD on the fate of epithelial cell isolated from human fetal palatal shelves (hFPECs). We demonstrate that TCDD increased cell proliferation and promoted the progression of cells from G1 to S phase as well as increased the number of cells entering the G2/M phase....
Source: Toxicology and Applied Pharmacology - June 12, 2016 Category: Toxicology Authors: Gao Z, Bu Y, Zhang G, Liu X, Wang X, Ding S, Wang E, Shi R, Li Q, Fu J, Yu Z Tags: Toxicol Appl Pharmacol Source Type: research

Epigenetic modification of miR-10a regulates renal damage by targeting CREB1 in type 2 diabetes mellitus.
In this study, we assessed the role of miR-10a in extracellular matrix accumulation in the kidney of diabetic mellitus induced by combining administration of chronic high fat diet (HFD) and low dosage of streptozotocin (STZ, 35mg/kg). Here, we found that HFD/STZ administration decreased the level of microRNA (miR-10a) expression in ICR strain mice. Overexpression of miR-10a alleviated the increased ratio of urine albumin-to-creatinine (ACR) ratio of HFD/STZ mice. In contrast, knockdown of miR-10a increased the ratio of kidney ACR in naïve mice. Furthermore, cAMP response element binding protein 1 (CREB1) was validated as ...
Source: Toxicology and Applied Pharmacology - June 8, 2016 Category: Toxicology Authors: Shan Q, Zheng G, Zhu A, Cao L, Lu J, Wu D, Zhang Z, Fan S, Sun C, Hu B, Zheng Y Tags: Toxicol Appl Pharmacol Source Type: research

Arsenic silences hepatic PDK4 expression through activation of histone H3K9 methylatransferase G9a.
Abstract It is well established that increased liver cancer incidence is strongly associated with epigenetic silencing of tumor suppressor genes; the latter is contributed by the environmental exposure to arsenic. Pyruvate dehydrogenase kinase 4 (PDK4) is a mitochondrial protein that regulates the TCA cycle. However, the epigenetic mechanisms mediated by arsenic to control PDK4 expression remain elusive. In the present study, we showed that histone methyltrasferase G9a- and Suv39H-mediated histone H3 lysine 9 (H3K9) methylations contributed to PDK4 silencing in hepatic cells. The PDK4 expression was induced by G9a...
Source: Toxicology and Applied Pharmacology - May 19, 2016 Category: Toxicology Authors: Zhang X, Wu J, Choiniere J, Yang Z, Huang Y, Bennett J, Wang L Tags: Toxicol Appl Pharmacol Source Type: research

Epigenetic silencing of miR-218 by the lncRNA CCAT1, acting via BMI1, promotes an altered cell cycle transition in the malignant transformation of HBE cells induced by cigarette smoke extract.
Abstract Cigarette smoking is the strongest risk factor for the development of lung cancer, the leading cause of cancer-related deaths. However, the molecular mechanisms leading to lung cancer are largely unknown. A long-noncoding RNA (lncRNA), CCAT1, regarded as cancer-associated, has been investigated extensively. Moreover, the molecular mechanisms of lncRNAs in regulation of microRNAs (miRNAs) induced by cigarette smoke remain unclear. In the present investigation, cigarette smoke extract (CSE) caused an altered cell cycle and increased CCAT1 levels and decreased miR-218 levels in human bronchial epithelial (HB...
Source: Toxicology and Applied Pharmacology - May 18, 2016 Category: Toxicology Authors: Lu L, Xu H, Luo F, Liu X, Lu X, Yang Q, Xue J, Chen C, Shi L, Liu Q Tags: Toxicol Appl Pharmacol Source Type: research