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https://www.readbyqxmd.com/read/28903497/downregulation-of-tmem70-in-rat-liver-cells-after-hepatocarcinogen-treatment-related-to-the-warburg-effect-in-hepatocarcinogenesis-producing-gst-p-expressing-proliferative-lesions
#1
Sayaka Mizukami, Yousuke Watanabe, Kota Nakajima, Yasuko Hasegawa-Baba, Meilan Jin, Toshinori Yoshida, Makoto Shibutani
We previously observed downregulation of mitochondrial oxidative phosphorylation-related protein, TMEM70, which is suggestive of disrupted cellular senescence, in GST-P-expressing (+) proliferative lesions from early hepatocarcinogenesis stages in rats. The present study investigated the immunohistochemical relationship between TMEM70 downregulation and cellular metabolic changes in carcinogenic processes, as well as the onset of the liver cell respiratory changes after repeated hepatocarcinogen treatment in rats...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28899750/downregulation-of-ube2e2-in-rat-liver-cells-after-hepatocarcinogen-treatment-facilitates-cell-proliferation-and-slowing-down-of-dna-damage-response-in-gst-p-expressing-preneoplastic-lesions
#2
Sayaka Mizukami, Yousuke Watanabe, Yukie Saegusa, Kota Nakajima, Yuko Ito, Yasunori Masubuchi, Toshinori Yoshida, Makoto Shibutani
We previously found downregulation of ubiquitin-conjugating enzyme E2E 2 (UBE2E2) in GST-P-expressing ((+)) proliferative lesions produced by tumor promotion from early hepatocarcinogenesis stages in rats. Here we investigated the role of UBE2E2 downregulation in preneoplastic lesions of the liver and other target organs produced by tumor promotion in rats. Increased number of UBE2E2-related ubiquitination target proteins, phosphorylated c-MYC, KDM4A and KMT5A, was found in the UBE2E2-downregulated GST-P-positive foci, compared with GST-P(+) foci expressing UBE2E2...
September 9, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28895767/promising-galactose-decorated-biodegradable-poloxamer-188-plga-diblock-copolymer-nanoparticles-of-resibufogenin-for-enhancing-liver-cancer-therapy
#3
Hao Dong, Li Tian, Meng Gao, Hong Xu, Chenghong Zhang, Li Lv, Jianbin Zhang, Changyuan Wang, Yan Tian, Xiaochi Ma
Liver cancer is one of the major diseases affecting human health. Modified drug delivery systems through the asialoglycoprotein receptor, which is highly expressed on the surface of hepatocytes, have become a research focus for the treatment of liver cancer. Resibufogenin (RBG) is a popular traditional Chinese medicine and natural anti-cancer drug that was isolated from Chansu, but its cardiotoxicity and hydrophobicity have limited its clinical applications. Galactosyl-succinyl-poloxamer 188 and galactosyl-succinyl-poloxamer 188-polylactide-co-glycolide (Gal-SP188-PLGA) were synthesized using galactose, P188, and PLGA to achieve active liver-targeting properties...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28884001/6-7-dimethoxy-1-2-3-4-tetrahydro-isoquinoline-3-carboxylic-acid-attenuates-heptatocellular-carcinoma-in-rats-with-nmr-based-metabolic-perturbations
#4
Pranesh Kumar, Ashok K Singh, Vinit Raj, Amit Rai, Siddhartha Maity, Atul Rawat, Umesh Kumar, Dinesh Kumar, Anand Prakash, Anupam Guleria, Sudipta Saha
AIM: 6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (M1) was synthesized and evaluated for in-vivo antiproliferative action in diethylnitrosamine-induced hepatocarcinogenic rats. MATERIALS & METHODS: The antiproliferative effect of M1 was assessed by various biochemical parameters, histopathology of liver and HPLC analysis. Proton nuclear magnetic resonance-based serum metabolic study was implemented on rat sera to explore the effects of M1 on hepatocellular carcinoma-induced metabolic alterations...
August 2017: Future Science OA
https://www.readbyqxmd.com/read/28802237/umbelliferon-%C3%AE-d-glucopyranosyl-2-i-%C3%A2-1-ii-%C3%AE-dglucopyranoside-ameliorates-diethylnitrosamine-induced-precancerous-lesion-development-in-liver-via-regulation-of-inflammation-hyperproliferation-and-antioxidant-at-pre-clinical-stage
#5
Vikas Kumar, Prakash Chandra Bhatt, Mahfoozur Rahman, Fahad A Al-Abbasi, Firoz Anwar, Amita Verma
It is well documented that anomalous production of inflammatory proteins linked with most of the toxic expression and genesis of diverse chronic disease including cancer. Diethylnitrosamine (DEN) a well-known hepatotoxin and hepatocarcinogen, can induce oxidative stress and inflammatory reaction in it. Umbelliferone, secondary metabolites, is present in different plants and widely consumed by humans as medicine and food supplements. The aim of the current study was to scrutinize the chemoprotective potential of umbelliferon-α-d-glucopyranosyl-(2(I)→1(II))-α-d-glucopyranoside (UFD) against DEN-induced hepatocellular carcinoma (HCC) in experimental rats...
August 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28662518/effects-of-n-nitrosodiethylamine-a-potent-carcinogen-on-sexual-development-gametogenesis-and-oocyte-maturation
#6
Reshma Nair U, Anju C Victor, Vinod Paul, Bindhu Paul-Prasanth
N-Nitrosodiethylamine (DEN), a well-known hepatocarcinogen, is found in certain food products as such or as a metabolic byproduct. This study investigated the effects of DEN on sexual development, gametogenesis, and oocyte maturation in Japanese medaka (Oryzias latipes). DEN reduced the germ cell number dose-dependently during early stages of sexual differentiation in XX larvae, resulting in underdeveloped ovaries in adulthood at low doses. This effect was sex-specific as no such changes were seen in XY larvae...
2017: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
https://www.readbyqxmd.com/read/28618930/gallic-acid-against-hepatocellular-carcinoma-an-integrated-scheme-of-the-potential-mechanisms-of-action-from-in-vivo-study
#7
Hadeer A Aglan, Hanaa H Ahmed, Sayed A El-Toumy, Nadia S Mahmoud
The global burden of hepatocellular carcinoma is increasing; actually, it is estimated as 750,000 new cases annually. This study was initiated to emphasize the possibility that gallic acid could alleviate hepatocarcinogenesis in vivo. In this study, 40 rats were enrolled and distributed as follows; group 1 was set as negative control, while all of groups 2, 3, and 4 were orally received N-nitrosodiethylamine for hepatocellular carcinoma induction. Group 2 was left untreated, whereas groups 3 and 4 were orally treated with gallic acid and doxorubicin, respectively...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28603212/effectiveness-of-the-liver-micronucleus-assay-using-juvenile-mice
#8
Ritsuko Nagasue, Ikue Murata, Kazuaki Sasaki, Rina Sakai, Hirofumi Miyajima, Minoru Shimoda
This study investigated the effectiveness of the liver micronucleus (MN) assay using juvenile mice. Therefore, we analyzed various hepatic cytochrome P450 (CYP)- mediated activities of ethoxyresorufin O-deethylation, pentoxyresorufin O-dealkylation, tolbutamide hydroxylation, bufuralol 1'-hydroxylation, aniline hydroxylation and midazolam 4-hydroxylation by CYP1A, CYP2B, CYP2C, CYP2D, CYP2E and CYP3A, respectively, in non-treated male ICR mice aged between 3 and 8 weeks. The enzyme efficiency levels in 3- and 4-week-old mice were approximately similar to or higher than those in 8-week-old mice, except for CYP1A and CYP2E in 3- and 4-week-old mice, respectively...
July 28, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28596526/mechanistic-roles-of-micrornas-in-hepatocarcinogenesis-a-study-of-thioacetamide-with-multiple-doses-and-time-points-of-rats
#9
Harsh Dweep, Yuji Morikawa, Binsheng Gong, Jian Yan, Zhichao Liu, Tao Chen, Halil Bisgin, Wen Zou, Huixiao Hong, Tieliu Shi, Ping Gong, Christina Castro, Takeki Uehara, Yuping Wang, Weida Tong
Environmental chemicals exposure is one of the primary factors for liver toxicity and hepatocarcinoma. Thioacetamide (TAA) is a well-known hepatotoxicant and could be a liver carcinogen in humans. The discovery of early and sensitive microRNA (miRNA) biomarkers in liver injury and tumor progression could improve cancer diagnosis, prognosis, and management. To study this, we performed next generation sequencing of the livers of Sprague-Dawley rats treated with TAA at three doses (4.5, 15 and 45 mg/kg) and four time points (3-, 7-, 14- and 28-days)...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28537892/effects-and-related-mechanisms-of-serotonin-on-malignant-biological-behavior-of-hepatocellular-carcinoma-via-regulation-of-yap
#10
Sushun Liu, Runchen Miao, Mimi Zhai, Qing Pang, Yan Deng, Sinan Liu, Kai Qu, Chang Liu, Jingyao Zhang
5-hydroxytryptamine (5-HT, serotonin) and Yes-associated protein (Yap), which act as a mitogen and an oncogene, respectively, play an important role in tumors. Here, we investigated whether 5-HT could affect the hepatocarcinogenic process via promoting the activation and expression of Yap, as well as the possible underlying molecular mechanisms. We found that 5-HT promoted hepatoma cell proliferation, invasion and metastasis via regulating Yap expression in vitro and in vivo, and Yap knockdown had opposite effects...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28502747/chicken-egg-fetal-liver-dna-and-histopathologic-effects-of-structurally-diverse-carcinogens-and-non-carcinogens
#11
M J Iatropoulos, T Kobets, J-D Duan, K D Brunnemann, E Vock, U Deschl, G M Williams
Chicken egg fetal livers were evaluated for histopathological changes produced by four genotoxic hepatocarcinogens: 2-acetylaminofluorene (AAF), aflatoxin B1 (AFB1), benzo[a]pyrene (BaP), diethylnitrosamine (DEN); four structurally related non- or weakly- carcinogenic comparators: fluorene (FLU), aflatoxin B2 (AFB2), benzo[e]pyrene (BeP), N-nitrosodiethanolamine (NDELA); two epigenetic hepatocarcinogens: clofibric acid (CFA), phenobarbital (PB); and the non-carcinogen, D-mannitol (MAN). CFA, PB and MAN were also assessed for formation of DNA adducts using the (32)P nucleotide postlabeling (NPL) assay and for DNA breaks using the comet assay...
May 11, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28479730/anti-hepatocarcinogenic-and-anti-oxidant-effects-of-mangrove-plant-scyphiphora-hydrophyllacea
#12
Sameera R Samarakoon, Chanthirika Shanmuganathan, Meran K Ediriweera, Poorna Piyathilaka, Kamani H Tennekoon, Ira Thabrew, Prasanna Galhena, E Dilip De Silva
CONTEXT: Scyphiphora hydrophyllacea is a shrub mangrove plant of the family Rubiaceae and not yet been studied for anti-hepatocarcinogenic effects. OBJECTIVES: We investigated possible in vitro anti-hepatocarcinogenic and antioxidant properties of S. hydrophyllacea. MATERIALS AND METHODS: Dried leaves of S. hydrophyllacea were sequentially extracted into hexane, chloroform, ethyl acetate, and methanol and tested for cytotoxicity on HepG2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and sulforhodamine B assays, and for antioxidant activities by the free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assays...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28326452/methyleugenol-dna-adducts-in-human-liver-are-associated-with-sult1a1-copy-number-variations-and-expression-levels
#13
Roman Tremmel, Kristin Herrmann, Wolfram Engst, Walter Meinl, Kathrin Klein, Hansruedi Glatt, Ulrich M Zanger
Methyleugenol is a rodent hepatocarcinogen occurring in many herbs and spices as well as essential oils used for flavoring. Following metabolic activation by cytochromes P450 (CYPs) and sulfotransferases (SULTs), methyleugenol can form DNA adducts. Previously, we showed that DNA adduct formation by methyleugenol in mouse liver is dependent on SULT1A1 expression and that methyleugenol DNA adducts are abundant in human liver specimens. In humans, SULT1A1 activity is affected by genetic polymorphisms, including single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs)...
March 22, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28218475/profound-changes-in-mirna-expression-during-cancer-initiation-by-aflatoxin-b1-and-their-abrogation-by-the-chemopreventive-triterpenoid-cddo-im
#14
Merricka C Livingstone, Natalie M Johnson, Bill D Roebuck, Thomas W Kensler, John D Groopman
Aflatoxin B1 (AFB1 ) is a potent human and animal hepatocarcinogen. To investigate the effects of aflatoxin on miRNA expression during the initiation phase of carcinogenesis, next-generation sequencing was used to analyze liver tissues from F344 rats exposed to 200 µg/kg per day AFB1 for 4 weeks. A panel of miRNAs was identified that was upregulated with AFB1 treatment compared to controls: rno-miR-434-3p, rno-miR-411-5p, rno-miR-221-3p, rno-miR-127-3p, rno-miR-205, rno-miR-429, rno-miR-34a-5p, rno-miR-181c-3p, rno-miR-200b-3p, and rno-miR-541-5p...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28198625/curcumin-attenuates-n-nitrosodiethylamine-induced-liver-injury-in-mice-by-utilizing-the-method-of-metabonomics
#15
Peiyu Qiu, Jiachen Sun, Shuli Man, He Yang, Long Ma, Peng Yu, Wenyuan Gao
N-Nitrosodiethylamine (DEN) exists as a food additive in cheddar cheese, processed meats, beer, water, and so forth. It is a potent hepatocarcinogen in animals and humans. Curcumin as a natural dietary compound decreased DEN-induced hepatocarcinogenesis in this research. According to the histopathological examination of liver tissues and biomarker detection in serum and livers, it was demonstrated that curcumin attenuated DEN-induced hepatocarcinogenesis through parts of regulating the oxidant stress enzymes (T-SOD and CAT), liver function (ALT and AST) and LDHA, AFP level, and COX-2/PGE2 pathway...
March 8, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28181396/the-aflatoxin-b1-fumonisin-b1-toxicity-in-brl-3a-hepatocytes-is-associated-to-induction-of-cytochrome-p450-activity-and-arachidonic-acid-metabolism
#16
Verónica S Mary, Silvina L Arias, Santiago N Otaiza, Pilar A Velez, Héctor R Rubinstein, Martín G Theumer
Human oral exposure to aflatoxin B1 (AFB1 ) and fumonisin B1 (FB1 ) is associated with increased hepatocellular carcinoma. Although evidence suggested interactive AFB1 -FB1 hepatotoxicity, the underlying mechanisms remain mostly unidentified. This work was aimed at evaluating the possible AFB1 -FB1 interplay to induce genetic and cell cycle toxicities in BRL-3A rat hepatocytes, reactive oxygen species (ROS) involvement, and the AFB1 metabolizing pathways cytochrome P450 (CYP) and arachidonic acid (ArAc) metabolism as ROS contributors...
June 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28131474/transcriptome-sequencing-reveals-prenatal-pfos-exposure-on-liver-disorders
#17
Keng Po Lai, Jing Woei Li, Angela Cheung, Rong Li, Md Baki Billah, Ting Fung Chan, Chris Kong Chu Wong
Perfluorooctane sulfonate (PFOS), a hepatic toxicant and a potential hepatocarcinogen, is commonly used in industrial products. The widespread contamination of PFOS in human maternal and cord blood has raised concerns about its potential risks to the fetus. It is believed that adverse environmental exposure during the critical period of embryo development can have long-lasting consequences in later life. In this report, we used transcriptome sequencing, followed by bioinformatics analysis, to elucidate the potential hepatotoxic and hepatocarcinogenic effects of prenatal PFOS exposure in the fetus...
April 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28130850/demethylating-and-anti-hepatocarcinogenic-potential-of-hesperidin-a-natural-polyphenol-of-citrus-juices
#18
Zahira Fernández-Bedmar, Jaouad Anter, Angeles Alonso-Moraga, Juana Martín de Las Mulas, Yolanda Millán-Ruiz, Silvia Guil-Luna
Hepatocellular carcinoma (HCC) is a neoplasia representing the fifth most common malignancy worldwide and the third cause of death from cancer. Diets with high content in fruits and vegetables are widely recommended for their health-promoting properties, among them, the protection against diabetes, cancer, and cardiovascular diseases. Hesperidin is the most important phenol in the orange fruit with well-known health benefits. Diet components have been used as possible modulator agents of DNA methylation in cancer cells and epigenetic therapy against their harmful effects could be a potential tool in chemotherapy...
June 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28123463/novel-protective-role-of-curcumin-and-taurine-combination-against-experimental-hepatocarcinogenesis
#19
Motawa Eisa El-Houseini, Ibrahim Ali El-Agoza, Mona Mohamed Sakr, Ghada Mohamed El-Malky
Hepatocarcinogenesis is a prerequisite to hepatocellular carcinoma (HCC), which is one of the most common cancers among humans. Therefore, it is important to search for agents that protect against hepatocarcinogenesis. The present study aimed to investigate the protective effects of a combination of taurine and curcumin against experimental hepatocarcinogenesis induced by diethyl nitrosamine (DENA) in a rat model. A total of 100 rats were divided into eight groups. Eight weeks following DENA injection and treatment with curcumin and taurine, the rats were sacrificed to obtain blood and hepatic tissue samples for the evaluation of various markers and histopathological observations...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28117354/identification-of-consensus-biomarkers-for-predicting-non-genotoxic-hepatocarcinogens
#20
Shan-Han Huang, Chun-Wei Tung
The assessment of non-genotoxic hepatocarcinogens (NGHCs) is currently relying on two-year rodent bioassays. Toxicogenomics biomarkers provide a potential alternative method for the prioritization of NGHCs that could be useful for risk assessment. However, previous studies using inconsistently classified chemicals as the training set and a single microarray dataset concluded no consensus biomarkers. In this study, 4 consensus biomarkers of A2m, Ca3, Cxcl1, and Cyp8b1 were identified from four large-scale microarray datasets of the one-day single maximum tolerated dose and a large set of chemicals without inconsistent classifications...
January 24, 2017: Scientific Reports
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