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Source: Toxicology and Applied Pharmacology

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Total 118 results found since Jan 2013.

Green tea polyphenol, (-)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting β-catenin signaling.
Abstract The green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), has been shown to have anti-carcinogenic effects in several skin tumor models, and efforts are continued to investigate the molecular targets responsible for its cytotoxic effects to cancer cells. Our recent observation that β-catenin is upregulated in skin tumors suggested the possibility that the anti-skin carcinogenic effects of EGCG are mediated, at least in part, through its effects on β-catenin signaling. We have found that treatment of the A431 and SCC13 human skin cancer cell lines with EGCG resulted in reduced cell viability and i...
Source: Toxicology and Applied Pharmacology - October 3, 2013 Category: Toxicology Authors: Singh T, Katiyar SK Tags: Toxicol Appl Pharmacol Source Type: research

Safflor yellow B suppresses angiotensin II-mediated human umbilical vein cell injury via regulation of Bcl-2/p22(phox) expression.
In this study, we examined the effects of SYB on Ang II-induced injury to human umbilical vein endothelial cells (HUVECs), and elucidated the roles of NADPH oxidase and Bcl-2. We treated cultured HUVECs with Ang II, SYB, and Bcl-2 siRNA, and determined NADPH oxidase activity and ROS levels. Furthermore, cellular and mitochondrial physiological states were evaluated, and the expression levels of target proteins were analyzed. Ang II significantly enhanced intracellular ROS levels, caused mitochondrial membrane dysfunction, and decreased cell viability, leading to apoptosis. This was associated with increased expression of A...
Source: Toxicology and Applied Pharmacology - August 28, 2013 Category: Toxicology Authors: Wang C, He Y, Yang M, Sun H, Zhang S, Wang C Tags: Toxicol Appl Pharmacol Source Type: research

Salvianolic acid A preconditioning confers protection against concanavalin A-induced liver injury through SIRT1-mediated repression of p66shc in mice.
Abstract Salvianolic acid A (SalA) is a phenolic carboxylic acid derivative extracted from Salvia miltiorrhiza. It has many biological and pharmaceutical activities. The purpose of this study was to investigate the effect of SalA on concanavalin A (ConA)-induced acute hepatic injury in Kunming mice and to explore the role of SIRT1 in such an effect. The results showed that in vivo pretreatment with SalA significantly reduced ConA-induced elevation in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and decreased levels of the hepatotoxic cytokines such as interferon-gamma (IFN-γ) and t...
Source: Toxicology and Applied Pharmacology - August 28, 2013 Category: Toxicology Authors: Xu X, Hu Y, Zhai X, Lin M, Chen Z, Tian X, Zhang F, Gao D, Ma X, Lv L, Yao J Tags: Toxicol Appl Pharmacol Source Type: research

Ethanol Increases Matrix Metalloproteinase-12 Expression via NADPH Oxidase-dependent ROS Production in Macrophages.
Abstract Matrix metalloproteinase-12 (MMP-12), an enzyme responsible for degradation of extracellular matrix, plays an important role in the progression of various diseases, including inflammation and fibrosis. Although most of those are pathogenic conditions induced by ethanol ingestion, the effect of ethanol on MMP-12 has not been explored. In the present study, we investigated the effect of ethanol on MMP-12 expression and its potential mechanisms in macrophages. Here, we demonstrated that ethanol treatment increased MMP-12 expression in primary murine peritoneal macrophages and RAW 264.7 macrophages both at mR...
Source: Toxicology and Applied Pharmacology - August 23, 2013 Category: Toxicology Authors: Kim MJ, Nepal S, Lee ES, Jeong TC, Kim SH, Park PH Tags: Toxicol Appl Pharmacol Source Type: research

TRPM7 channel regulates PDGF-BB-induced proliferation of hepatic stellate cells via PI3K and ERK pathways.
Abstract TRPM7, a non-selective cation channel of the TRP channel superfamily, is implicated in diverse physiological and pathological processes including cell proliferation. Recently, TRPM7 has been reported in hepatic stellate cells (HSCs). Here, we investigated the contribution role of TRPM7 in activated HSC-T6 cells (a rat hepatic stellate cell line) proliferation. TRPM7 mRNA and protein was measured by RT-PCR and Western blot in rat model of liver fibrosis in vivo and PDGF-BB-activated HSC-T6 cells in vitro. Both mRNA and protein of TRPM7 were dramatically increased in CCl4-treated rat livers. Stimulation of ...
Source: Toxicology and Applied Pharmacology - August 16, 2013 Category: Toxicology Authors: Fang L, Zhan S, Huang C, Cheng X, Lv X, Si H, Li J Tags: Toxicol Appl Pharmacol Source Type: research

Teroxirone inhibited growth of human non-small cell lung cancer cells by activating p53.
Abstract In this work, we demonstrated that the growth of human non-small-cell-lung-cancer cells H460 and A549 cells can be inhibited by low concentrations of an epoxide derivative, teroxirone, in both in vitro and in vivo models. The cytotoxicity was mediated by apoptotic cell death through DNA damage. The onset of ultimate apoptosis is dependent on the status of p53. Teroxirone caused transient elevation of p53 that activates downstream p21 and procaspase-3 cleavage. The presence of caspase-3 inhibitor reverted apoptotic phenotype. Furthermore, we showed the cytotoxicity of teroxirone in H1299 cells with stable ...
Source: Toxicology and Applied Pharmacology - August 15, 2013 Category: Toxicology Authors: Wang JP, Lin KH, Liu CY, Yu YC, Wu PT, Chiu CC, Su CL, Chen KM, Fang K Tags: Toxicol Appl Pharmacol Source Type: research

Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth.
In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. PMID: 23954465 [PubMed - as supplied by publisher]
Source: Toxicology and Applied Pharmacology - August 15, 2013 Category: Toxicology Authors: Hsu YY, Tseng YT, Lo YC Tags: Toxicol Appl Pharmacol Source Type: research

Curcumin analogue 1, 5-Bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibit enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE-19 cell toxicity.
Abstract Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin have been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analogue, 1, 5-Bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human...
Source: Toxicology and Applied Pharmacology - August 13, 2013 Category: Toxicology Authors: Li Y, Zou X, Cao K, Xu J, Yue T, Dai F, Zhou B, Lu W, Feng Z, Liu J Tags: Toxicol Appl Pharmacol Source Type: research

Ghrelin inhibits the apoptosis of MC3T3-E1 cells through ERK and AKT signaling pathway.
In conclusion, ghrelin inhibits the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, which may be mediated by activating the GHSR/ERK and GHSR/PI3K/AKT signaling pathways. PMID: 23921150 [PubMed - as supplied by publisher]
Source: Toxicology and Applied Pharmacology - August 3, 2013 Category: Toxicology Authors: Liang QH, Liu Y, Wu SS, Cui RR, Yuan LQ, Liao EY Tags: Toxicol Appl Pharmacol Source Type: research

Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation.
Abstract Gossypetin, a flavone originally isolated from Hibiscus species, has been shown to possess antioxidant, antimicrobial, and antimutagenic activities. Here, we investigated the mechanism(s) underlying the anti-atherosclerotic potential of gossypetin. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay showed that the addition of >50μM of gossypetin could scavenge over 50% of DPPH radicals. The inhibitory effects of gossypetin on the lipid and protein oxidation of LDL were defined by thiobarbituric acid reactive substance (TBARS) assay, the relative electrophoretic mobility (REM) of oxidized L...
Source: Toxicology and Applied Pharmacology - July 8, 2013 Category: Toxicology Authors: Chen JH, Tsai CW, Wang CP, Lin HH Tags: Toxicol Appl Pharmacol Source Type: research

Newly synthesized quinazolinone HMJ-38 suppresses angiogenetic responses and triggers human umbilical vein endothelial cell apoptosis through p53-modulated Fas/death receptor signaling.
Abstract The current study aims to investigate the antiangiogenic responses and apoptotic death of human umbilical vein endothelial cells (HUVECs) by a newly synthesized compound named 2-(3'-methoxyphenyl)-6-pyrrolidinyl-4-quinazolinone (HMJ-38). This work attempted to not only explore the effects of angiogenesis on in vivo and ex vivo studies but also hypothesize the implications for HUVECs (an ideal cell model for angiogenesis in vitro) and further undermined apoptotic experiments to verify the underlying molecular signaling by HMJ-38. Our results demonstrated that HMJ-38 significantly inhibited blood vessel gro...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Chiang JH, Yang JS, Lu CC, Hour MJ, Chang SJ, Lee TH, Chung JG Tags: Toxicol Appl Pharmacol Source Type: research

Resveratrol inhibits LXRα-dependent hepatic lipogenesis through novel antioxidant Sestrin2 gene induction.
This study investigated the effect of resveratrol in LXRα-mediated lipogenesis and the underlying molecular mechanism. Resveratrol inhibited the ability of LXRα to activate sterol regulatory element binding protein-1c (SREBP-1c) and thereby inhibited target gene expression in hepatocytes. Moreover, resveratrol decreased LXRα-RXRα DNA binding activity and LXRE-luciferase transactivation. Resveratrol is known to activate Sirtuin 1 (Sirt1) and AMP-activated protein kinase (AMPK), although its precise mechanism of action remains controversial. We found that the ability of resveratrol to repress T0901317-induced SREBP-1c ex...
Source: Toxicology and Applied Pharmacology - May 5, 2013 Category: Toxicology Authors: Jin SH, Yang JH, Shin BY, Seo K, Shin SM, Cho IJ, Ki SH Tags: Toxicol Appl Pharmacol Source Type: research

Epithelial to mesenchymal transition in arsenic-transformed cells promotes angiogenesis through activating β-catenin-vascular endothelial growth factor pathway.
The objective of this study was to investigate the effect of arsenic-transformed human bronchial epithelial cells that underwent EMT on angiogenesis and the underlying mechanism. It was found that the conditioned medium from arsenic-transformed cells strongly stimulated tube formation by human umbilical vein endothelial cells (HUVECs). Moreover, enhanced angiogenesis was detected in mouse xenograft tumor tissues resulting from inoculation of arsenic-transformed cells. Mechanistic studies revealed that β-catenin was activated in arsenic-transformed cells up-regulating its target gene expression including angiogenic-stimula...
Source: Toxicology and Applied Pharmacology - April 30, 2013 Category: Toxicology Authors: Wang Z, Humphries B, Xiao H, Jiang Y, Yang C Tags: Toxicol Appl Pharmacol Source Type: research