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Source: Toxicology and Applied Pharmacology

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Total 118 results found since Jan 2013.

Contact allergen (PPD and DNCB)-induced keratinocyte sensitization is partly mediated through a low molecular weight hyaluronan (LMWHA)/TLR4/NF- κB signaling axis.
In conclusion, keratinocyte contact allergen-dependent sensitization is partly mediated through a LMWHA/TLR4/ NF-κB signaling axis. PMID: 31226360 [PubMed - as supplied by publisher]
Source: Toxicology and Applied Pharmacology - June 17, 2019 Category: Toxicology Authors: Kavasi RM, Berdiaki A, Spyridaki I, Papoutsidakis A, Corsini E, Tsatsakis A, Tzanakakis G, Dragana N Tags: Toxicol Appl Pharmacol Source Type: research

Induction of endoplasmic reticulum stress might be responsible for defective autophagy in cadmium-induced prostate carcinogenesis.
Abstract Earlier, we reported that chronic cadmium (Cd)-exposure to prostate epithelial (RWPE-1) cells causes defective autophagy, which leads to the transformation of a malignant phenotype in both in vitro and in vivo models. However, the upstream events responsible for defective autophagy are yet to be delineated. The present study suggests that chronic Cd exposure induces endoplasmic reticulum (ER) stress that triggers the phosphorylation of stress transducers [protein kinase R-like ER Kinase- (PERK), eukaryotic translation initiation factor 2-alpha- (eIF2-α) and Activating Transcription Factor 4 -(ATF-4)], re...
Source: Toxicology and Applied Pharmacology - April 15, 2019 Category: Toxicology Authors: Kolluru V, Tyagi A, Chandrasekaran B, Ankem M, Damodaran C Tags: Toxicol Appl Pharmacol Source Type: research

Inhibition of miR-23a attenuates doxorubicin-induced mitochondria-dependent cardiomyocyte apoptosis by targeting the PGC-1 α/Drp1 pathway.
CONCLUSIONS AND IMPLICATIONS: Increased miR-23a promoted mitochondrial injury in the Dox-induced cellular model. Inhibition of miR-23a attenuated cardiomyocyte damage by directly targeting PGC-1α/p-Drp1, thereby inhibiting mitochondria-dependent apoptosis. These findings may provide a new potential target for the treatment of Dox-induced cardiotoxicity. PMID: 30831132 [PubMed - as supplied by publisher]
Source: Toxicology and Applied Pharmacology - February 28, 2019 Category: Toxicology Authors: Du J, Hang P, Pan Y, Feng B, Zheng Y, Chen T, Zhao L, Du Z Tags: Toxicol Appl Pharmacol Source Type: research

Nicotinamide mononucleotide alleviates Aluminum induced bone loss by inhibiting the TXNIP-NLRP3 inflammasome.
Abstract Aluminum (Al) recognized as a persistent environmental contaminant is associated with bone diseases. Nicotinamide mononucleotide (NMN) is an intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis widely used to replenish NAD+. Increasing evidences demonstrated that replenishment of NAD+ can protect against bone loss. However, the potentially protective effects of NMN against Al-induced bone impairment and the underlying mechanisms remain unknown. In the present study, we sought to investigate the protective effects of NMN on Al-induced bone damages and elucidate the potential mechanisms. We...
Source: Toxicology and Applied Pharmacology - October 4, 2018 Category: Toxicology Authors: Liang H, Gao J, Zhang C, Li C, Wang Q, Fan J, Wu Z, Wang Q Tags: Toxicol Appl Pharmacol Source Type: research

Role of Mcl-1 in regulation of cell death in human induced pluripotent stem cell-derived cardiomyocytes in vitro.
Abstract Targeting the anti-apoptotic protein Mcl-1 holds a promise to improve therapy of multiple types of Mcl-1 dependent cancers but raises concerns of on-target cardiotoxicity due to the presence and reported role of Mcl-1 in heart. Herein, we investigated the importance of Mcl-1 in the survival and contractile function of human pluripotent stem cell-derived cardiomyocytes in culture. Effective knockdown of Mcl-1 with siRNAs reproducibly resulted in early (measured at Day 3) marginal alterations in caspase 3/7 activity, LDH leakage, ATP content and cellular impedance. After 14 days of Mcl-1 knockdown, loss o...
Source: Toxicology and Applied Pharmacology - September 27, 2018 Category: Toxicology Authors: Guo L, Eldridge S, Furniss M, Mussio J, Davis M Tags: Toxicol Appl Pharmacol Source Type: research

Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces hepatic steatosis and endoplasmic reticulum stress by inducing nuclear factor erythroid-derived 2-related factor 2 nuclear translocation.
Abstract Activation of endoplasmic reticulum (ER) stress is involved in the development of nonalcoholic fatty liver disease. Glucagon-like peptide-1 (GLP-1) has been reported to reduce hepatic steatosis, but the underlying mechanism has not been fully elucidated. Here, we investigated whether exendin-4 (EX-4), a GLP-1 receptor analogue, improves hepatic steatosis through ER stress reduction. Furthermore, we explored which ER stress pathway is involved in this process, with a focus on the protein kinase RNA-like ER kinase (PERK)-nuclear factor erythroid-derived 2-related factor 2 (Nrf2) pathway. EX-4 treatment redu...
Source: Toxicology and Applied Pharmacology - September 22, 2018 Category: Toxicology Authors: Yoo J, Cho IJ, Jeong IK, Ahn KJ, Chung HY, Hwang YC Tags: Toxicol Appl Pharmacol Source Type: research

Raddeanin A, a natural triterpenoid saponin compound, exerts anticancer effect on human osteosarcoma via the ROS/JNK and NF- κB signal pathway.
Raddeanin A, a natural triterpenoid saponin compound, exerts anticancer effect on human osteosarcoma via the ROS/JNK and NF-κB signal pathway. Toxicol Appl Pharmacol. 2018 May 27;: Authors: Ma B, Zhu J, Zhao A, Zhang J, Wang Y, Zhang H, Zhang L, Zhang Q Abstract Osteosarcoma (OS) is the most frequent and high mortality primary bone tumor in the adolescent. And it is well-known for poor prognosis due to high incidence of metastasis. Raddeanin A (RA), an active component of Anemone raddeana Regel, showed potential anti-cancer activities. However, the anti-tumor effect and molecular mechanism(s) of RA o...
Source: Toxicology and Applied Pharmacology - May 27, 2018 Category: Toxicology Authors: Ma B, Zhu J, Zhao A, Zhang J, Wang Y, Zhang H, Zhang L, Zhang Q Tags: Toxicol Appl Pharmacol Source Type: research

cAMP/PKA/EGR1 signaling mediates the molecular mechanism of ethanol-induced inhibition of placental 11 β-HSD2 expression.
This study aimed to investigate the molecular mechanism of the prenatal ethanol exposure (PEE)-induced inhibition of placental 11β-HSD2 expression. Pregnant Wistar rats were intragastrically administered ethanol (4 g/kg d) from gestational days 9 to 20. The levels of maternal and fetal serum corticosterone and placental 11β-HSD2-related gene expression were analyzed. Furthermore, we investigated the mechanism of reduced placental 11β-HSD2 expression induced by ethanol treatment (15-60 mM) in HTR-8/SVneo cells. In vivo, PEE decreased fetal body weights and increased maternal and fetal serum corticosterone and early...
Source: Toxicology and Applied Pharmacology - May 23, 2018 Category: Toxicology Authors: Yu L, Zhou J, Zhang G, Huang W, Pei L, Lv F, Zhang Y, Zhang W, Wang H 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

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

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

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

Carnosic acid prevents COL1A2 transcription through the reduction of Smad3 acetylation via the AMPK α1/SIRT1 pathway.
Carnosic acid prevents COL1A2 transcription through the reduction of Smad3 acetylation via the AMPKα1/SIRT1 pathway. Toxicol Appl Pharmacol. 2017 Dec 15;: Authors: Zhao Y, Shi X, Ding C, Feng D, Li Y, Hu Y, Wang L, Gao D, Tian X, Yao J Abstract Carnosic acid (CA), a major bioactive component in rosemary extract, has many biological and pharmaceutical activities. Smad3 acetylation can regulate the transcription of type I α2 collagen (COL1A2), which is the major component of the extracellular matrix (ECM). The aim of the current study was to evaluate whether CA inhibits COL1A2 transcription via the re...
Source: Toxicology and Applied Pharmacology - December 15, 2017 Category: Toxicology Authors: Zhao Y, Shi X, Ding C, Feng D, Li Y, Hu Y, Wang L, Gao D, Tian X, Yao J 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

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