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https://www.readbyqxmd.com/read/29722557/augmentation-of-diethylnitrosamine-induced-early-stages-of-rat-hepatocarcinogenesis-by-1-2-dimethylhydrazine
#1
Charatda Punvittayagul, Arpamas Chariyakornkul, Teera Chewonarin, Kanokwan Jarukamjorn, Rawiwan Wongpoomchai
Diethylnitrosamine (DEN) and 1,2-dimethylhydrazine (DMH) are classical carcinogens used in experimental rodent carcinogenesis. However, the interaction effects of these carcinogens on biochemical and molecular changes during carcinogenesis have not been investigated. Therefore, the effect of DEN and DMH co-administration on preneoplastic lesion formation and its molecular mechanism in rats were determined. Triple intraperitoneal administrations of DEN were made before, during or after double subcutaneous injections of DMH...
May 3, 2018: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29716964/nuclear-receptor-car-suppresses-gadd45b-p38-mapk-signaling-to-promote-phenobarbital-induced-proliferation-in-mouse-liver
#2
Takeshi Hori, Kosuke Saito, Rick Moore, Gordon P Flake, Masahiko Negishi
Phenobarbital (PB), a non-genotoxic hepatocarcinogen, induces hepatic proliferation and promotes development of hepatocellular carcinoma (HCC) in rodents. Nuclear receptor constitutive active/androstane receptor (NR1I3/CAR) regulates the induction and promotion activities of PB. Here, it is demonstrated that PB treatment results in dephosphorylation of a tumor suppressor p38 mitogen-activated protein kinase (MAPK) in the liver of C57BL/6 and C3H/HeNCrlBR mice. The molecular mechanism entails CAR binding and inhibition of the growth arrest and DNA-damage-inducible 45 beta (GADD45B)-MAPK kinase 6 (MKK6) scaffold to repress phosphorylation of p38 MAPK...
May 1, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29695134/label-free-impedance-sensing-of-aflatoxin-b%C3%A2-with-polyaniline-nanofibers-au-nanoparticle-electrode-array
#3
Ajay Kumar Yagati, Sachin Ganpat Chavan, Changyoon Baek, Min-Ho Lee, Junhong Min
Aflatoxin B1 (AFB₁) is produced by the Aspergillus flavus and Aspergillus parasiticus group of fungi which is most hepatotoxic and hepatocarcinogenic and occurs as a contaminant in a variety of foods. AFB₁ is mutagenic, teratogenic, and causes immunosuppression in animals and is mostly found in peanuts, corn, and food grains. Therefore, novel methodologies of sensitive and expedient strategy are often required to detect mycotoxins at the lowest level. Herein, we report an electrochemical impedance sensor that selectively detects AFB₁ at the lowest level by utilizing polyaniline nanofibers (PANI) coated with gold (Au) nanoparticles composite based indium tin oxide (ITO) disk electrodes...
April 24, 2018: Sensors
https://www.readbyqxmd.com/read/29626562/a-human-relevance-investigation-of-ppar%C3%AE-mediated-key-events-in-the-hepatocarcinogenic-mode-of-action-of-propaquizafop-in-rats
#4
Christian Strupp, Werner H Bomann, François Spézia, Frédéric Gervais, Roy Forster, Lysiane Richert, Pramila Singh
Propaquizafop is an herbicide with demonstrated hepatocarcinogenic activity in rodents. A rodent-specific mode of action (MOA) in the liver via activation of peroxisome proliferator-activated receptor α (PPARα) has been postulated based on existing data. Experience with PPARα-inducing pharmaceuticals indicates a lack of human relevance of this MOA. The objective of the present investigation was to evaluate the dependency of early key events leading to liver tumors on PPARα activation in wildtype (WT) compared to PPARα-knockout (KO) rats following 2 weeks exposure to 75, 500 and 1000 ppm propaquizafop in the diet...
April 4, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29556478/dose-dependent-effects-on-rat-liver-mirnas-200a-b-and-429-potential-early-biomarkers-of-liver-carcinogenesis
#5
S M Plummer, J Wright, R A Currie
An increased incidence of liver tumours in the long term rodent bioassay is not an uncommon finding, invariably as a result of a non-genotoxic mode of action. Non-genotoxic liver carcinogenesis has been found to involve activation of certain nuclear hormone receptors (NHR) including the constitutive androstane receptor (CAR), peroxisome proliferator activated receptor alpha (PPARalpha) and arylhydrocarbon receptor (AHR) and more recently the induction of specific microRNAs (miRs), has also been demonstrated following CAR activation in studies up to 90 days (Koufaris et al...
2018: Toxicology Reports
https://www.readbyqxmd.com/read/29533866/aflatoxin-b-1-exposure-increases-the-risk-of-hepatocellular-carcinoma-associated-with-hepatitis-c-virus-infection-or-alcohol-consumption
#6
Yu-Ju Chu, Hwai-I Yang, Hui-Chen Wu, Mei-Hsuan Lee, Jessica Liu, Li-Yu Wang, Sheng-Nan Lu, Chin-Lan Jen, San-Lin You, Regina M Santella, Chien-Jen Chen
BACKGROUND: Hepatocarcinogenicity of aflatoxin B1 (AFB1 ) has rarely been studied in populations with hepatitis C virus (HCV) infection and those without hepatitis B virus (HBV) and HCV infection (non-B-non-C). This case-control study nested in a community-based cohort aimed to investigate the HCC risk associated with AFB1 in HCV-infected and non-B-non-C participants. METHODS: Baseline serum AFB1 -albumin adduct levels were measured in 100 HCC cases and 1767 controls seronegative for anti-HCV and HBsAg (non-B-non-C), and another 103 HCC cases and 176 controls who were anti-HCV-seropositive and HBsAg-seronegative...
May 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29477305/a-metabolomic-approach-to-identify-anti-hepatocarcinogenic-compounds-from-plants-used-traditionally-in-the-treatment-of-liver-diseases
#7
François Chassagne, Mohamed Haddad, Aurélien Amiel, Chiobouaphong Phakeovilay, Chanthanom Manithip, Geneviève Bourdy, Eric Deharo, Guillaume Marti
Liver cancer is a major health burden in Southeast Asia, and most patients turn towards the use of medicinal plants to alleviate their symptoms. The aim of this work was to apply to Southeast Asian plants traditionally used to treat liver disorders, a successive ranking strategy based on a comprehensive review of the literature and metabolomic data in order to relate ethnopharmacological relevance to chemical entities of interest. We analyzed 45 publications resulting in a list of 378 plant species, and our point system based on the frequency of citation in the literature allowed the selection of 10 top ranked species for further collection and extraction...
February 23, 2018: Fitoterapia
https://www.readbyqxmd.com/read/29351317/hafts-are-novel-lncrna-transcripts-from-aflatoxin-exposure
#8
B Alex Merrick, Justin S Chang, Dhiral P Phadke, Meredith A Bostrom, Ruchir R Shah, Xinguo Wang, Oksana Gordon, Garron M Wright
The transcriptome can reveal insights into precancer biology. We recently conducted RNA-Seq analysis on liver RNA from male rats exposed to the carcinogen, aflatoxin B1 (AFB1), for 90 days prior to liver tumor onset. Among >1,000 differentially expressed transcripts, several novel, unannotated Cufflinks-assembled transcripts, or HAfTs (Hepatic Aflatoxin Transcripts) were found. We hypothesized PCR-cloning and RACE (rapid amplification of cDNA ends) could further HAfT identification. Sanger data was obtained for 6 transcripts by PCR and 16 transcripts by 5'- and 3'-RACE...
2018: PloS One
https://www.readbyqxmd.com/read/29328669/urinary-methyleugenol-deoxyadenosine-adduct-as-a-potential-biomarker-of-methyleugenol-exposure-in-rats
#9
Yukun Feng, Saide Wang, Hui Wang, Ying Peng, Jiang Zheng
Methyleugenol (ME), a natural ingredient of several herbs and spices used in the human diet, is hepatocarcinogenic in rodents. Following metabolic activation to the reactive carbocation intermediate, ME can bind covalently to DNA, which is directly associated with its carcinogenicity. In this work, a non-invasive approach to determine ME exposure was established by monitoring the urinary N6 -(methylisoeugenol-3'-yl)-2'-deoxyadenosine (ME-dA) adduct. The developed method entails liquid-liquid extraction enrichment of urinary ME-dA, incorporation of deuterated ME-dA as an internal standard, and analysis by liquid chromatography coupled tandem mass spectrometry...
February 7, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29319795/n-acetyl-2-aminofluorene-aaf-processing-in-adult-rat-hepatocytes-in-primary-culture-occurs-by-high-affinity-low-velocity-and-low-affinity-high-velocity-aaf-metabolite-forming-systems
#10
K S Koch, T Moran, W T Shier, H L Leffert
N-acetyl-2-aminofluorene (AAF) is a procarcinogen used widely in physiological investigations of chemical hepatocarcinogenesis. Its metabolic pathways have been described extensively, yet little is known about its biochemical processing, growth cycle expression and pharmacological properties inside living hepatocytes - the principal cellular targets of this hepatocarcinogen. In this report, primary monolayer adult rat hepatocyte cultures and high specific-activity [ring G-3H]-N-acetyl-2-aminofluorene were used to extend previous observations of metabolic activation of AAF by highly differentiated, proliferation-competent hepatocytes in long-term cultures...
January 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29245921/aflatoxin-b-1-affects-apoptosis-and-expression-of-death-receptor-and-endoplasmic-reticulum-molecules-in-chicken-spleen
#11
Panpan Zhu, Zhicai Zuo, Zhixiang Zheng, Fengyuan Wang, Xi Peng, Jing Fang, Hengmin Cui, Caixia Gao, Hetao Song, Yi Zhou, Xici Liu
Aflatoxin B1 (AFB1 ) is a natural product of the Aspergillus genus of molds, which grow on several foodstuffs stored in hot moist conditions, and is among the most potent hepatocarcinogens and immunosuppression presently known. The latter was related to the up-regulated apoptosis of immune organs. However, the effect of expression of death receptor and endoplasmic reticulum molecules in AFB1 -induced apoptosis of chicken splenocytes was largely unknown. The objective of this study was to investigate this unknown field...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29233689/in-vitro-toxicity-evaluation-of-estragole-containing-preparations-derived-from-foeniculum-vulgare-mill-fennel-on-hepg2-cells
#12
Sara Levorato, Luca Dominici, Cristina Fatigoni, Claudia Zadra, Rita Pagiotti, Massimo Moretti, Milena Villarini
Estragole, a common component of herbs and spices, is a wellknown genotoxic hepatocarcinogen in rodents, whereas its potential toxic effect in humans is still debated. In the European contest, one of the major sources of human exposure to this phytochemical is Foeniculum vulgare Mill. (fennel). Therefore, the aim of this study was to evaluate the in vitro toxicity of estragole in the context of two complex phytochemical mixtures derived from fennel: fennel seed powder (FSPw) and fennel seed essential oil (FSEO)...
January 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29142176/evaluation-of-the-human-relevance-of-the-constitutive-androstane-receptor-mediated-mode-of-action-for-rat-hepatocellular-tumor-formation-by-the-synthetic-pyrethroid-momfluorothrin
#13
Yu Okuda, Masahiko Kushida, Hiroko Kikumoto, Yoshimasa Nakamura, Hashihiro Higuchi, Satoshi Kawamura, Samuel M Cohen, Brian G Lake, Tomoya Yamada
High dietary levels of the non-genotoxic synthetic pyrethroid momfluorothrin increased the incidence of hepatocellular tumors in male and female Wistar rats. Mechanistic studies have demonstrated that the mode of action (MOA) for momfluorothrin-induced hepatocellular tumors is constitutive androstane receptor (CAR)-mediated. In the present study, to evaluate the potential human carcinogenic risk of momfluorothrin, the effects of momfluorothrin (1-1,000 µM) and a major metabolite Z-CMCA (5-1,000 µM) on hepatocyte replicative DNA synthesis and CYP2B mRNA expression were examined in cultured rat and human hepatocyte preparations...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29128613/submicromolar-bisphenol-a-induces-proliferation-and-dna-damage-in-human-hepatocyte-cell-lines-in-vitro-and-in-juvenile-rats-in-vivo
#14
Seoyoung Kim, Gil-Im Mun, Eun Choi, Minjeong Kim, Ji Seong Jeong, Keon Wook Kang, Sunha Jee, Kyung-Min Lim, Yun-Sil Lee
An association between bisphenol A (BPA) exposure and hepatic tumors was suggested, but the employment of high-dose levels raises questions about its relevance to human health. Here, we demonstrate that submicromolar concentrations of BPA induce the proliferation and DNA damage in human hepatocyte cell lines. In HepG2 and NKNT-3, undifferentiated and differentiated hepatocyte cell lines, respectively, submicromolar BPA concentrations promoted the cell proliferation, as indicated by enhanced DNA synthesis and elevated expression of cell-cycle proteins...
January 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29115890/exploiting-bilosomes-for-delivering-bioactive-polysaccharide-isolated-from-enteromorpha-intestinalis-for-hacking-hepatocellular-carcinoma
#15
Azza Abdelmageed Matloub, Alaa Hamed Salama, Hadeer Ahmed Aglan, Mona Mahmoud AbouSamra, Sahar Salah Mohamed ElSouda, Hanaa Hamdy Ahmed
Bile salts containing vesicles (bilosomes) represent a portentous vesicular carrier that showed prosperous results in delivering active moieties in the gastrointestinal tract (GIT). In this study, bilosomes were exploited to deliver sulfated polysaccharide-protein complexes of Enteromorpha intestinalis (EHEM) and enhance its activity against hepatocellular carcinoma as well as resist harsh GIT conditions. Bilosomes were prepared using the sodium salt of three different bile acids (cholic, deoxycholic, taurodeoxycholic) and two different nonionic surfactants (Span 40 and 65)...
April 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29054680/phosphorylation-of-protein-phosphatase-2a-facilitated-an-early-stage-of-chemical-carcinogenesis
#16
Yuji Ishii, Ken Kuroda, Kohei Matsushita, Yuh Yokoo, Shinji Takasu, Aki Kijima, Takehiko Nohmi, Kumiko Ogawa, Takashi Umemura
Protein phosphatase 2A (PP2A) is a serine-threonine phosphatase that regulates cell signaling pathways. Its inactivation is correlated with tumor malignancy, possibly due to the effects on cell differentiation and malignant cell transformation. Therefore, it has been noted that PP2A could be a promising target for cancer therapy. In our previous study of the hepatocarcinogen estragole (ES), cell proliferation may be required to convert ES-specific DNA adducts to mutations. To explore the trigger for cell proliferation, gpt delta rats were administered ES by gavage at doses of 3, 30 and 300mg/kg/day for 4weeks...
December 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28987376/pyrrolizidine-alkaloid-derived-dna-adducts-are-common-toxicological-biomarkers-of-pyrrolizidine-alkaloid-n-oxides
#17
Xiaobo He, Qingsu Xia, Kellie Woodling, Ge Lin, Peter P Fu
There are 660 pyrrolizidine alkaloids (PAs) and PA N-oxides present in the plants, with approximately half being possible carcinogens. We previously reported that a set of four PA-derived DNA adducts is formed in the liver of rats administered a series of hepatocarcinogenic PAs and a PA N-oxide. Based on our findings, we hypothesized that this set of DNA adducts is a common biological biomarker of PA-induced liver tumor formation. In this study, we determined that rat liver microsomal metabolism of five hepatocarcinogenic PAs (lasiocarpine, retrorsine, riddelliine, monocrotaline, and heliotrine) and their corresponding PA N-oxides produced the same set of DNA adducts...
October 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28973694/editor-s-highlight-pregnancy-alters-aflatoxin-b1-metabolism-and-increases-dna-damage-in-mouse-liver
#18
Kanokwan Sriwattanapong, Stephen L Slocum, Supawadee Chawanthayatham, Bogdan I Fedeles, Patricia A Egner, John D Groopman, Jutamaad Satayavivad, Robert G Croy, John M Essigmann
Pregnancy is a complex physiological state, in which the metabolism of endogenous as well as exogenous agents is ostensibly altered. One exogenous agent of concern is the hepatocarcinogen aflatoxin B1 (AFB1), a foodborne fungal toxin, that requires phase I metabolic oxidation for conversion to its toxic and carcinogenic form, the AFB1-8,9-exo-epoxide. The epoxide interacts with cellular targets causing toxicity and cell death; these targets include the covalent modification of DNA leading to mutations that can initiate malignant transformation...
November 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28935588/effect-of-methapyrilene-hydrochloride-on-hepatic-intracellular-iron-metabolism-in-vivo-and-in-vitro
#19
Iryna Kindrat, Kostiantyn Dreval, Svitlana Shpyleva, Volodymyr Tryndyak, Aline de Conti, Thilak K Mudalige, Tao Chen, Anna M Erstenyuk, Frederick A Beland, Igor P Pogribny
The liver, a central detoxification organ and main regulator of systemic iron homeostasis, is prone to damage by xenobiotics. In the present study, we investigated the effect of the hepatotoxicant and hepatocarcinogen methapyrilene hydrochloride on iron metabolism in rat liver in a repeat-dose in vivo toxicity study and in human HepaRG cells in vitro. Treatment of male Fischer 344 (F344) rats with methapyrilene at doses 40 and 80mg/kg body weight (bw)/day by gavage for 6 weeks resulted in changes in the expression of classic hepatotoxicity-related marker genes and iron homeostasis-related genes, especially a prominent, dose-dependent down-regulation of the transferrin (Tf) gene and an up-regulation of the ferritin, light chain (Ftl) gene...
November 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28927250/gut-microbiota-and-the-liver
#20
Alessandro Federico, Marcello Dallio, Giuseppe G Caprio, Vittorio M Ormando, Carmela Loguercio
Nowadays liver diseases represent one of major healthy problems in the world in terms of morbidity and mortality. The high prevalence of liver pathologies represents the key point to understand the necessity to identify the pathogenetic mechanisms that support these disorders in order to nurse them. Alterations of intestinal microbiota seem to play an important role in induction and promotion of liver damage progression, in addition to direct injury resulting from different causal agents. Gut microbiota is considered both as a promoting factor and as a potential therapeutic target of a large number of liver pathologies due to the connection between intestine and liver: the gut-liver axis...
December 2017: Minerva Gastroenterologica e Dietologica
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