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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
#1
Seoyoung Kim, Gilim 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...
November 8, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29115890/exploiting-bilosomes-for-delivering-bioactive-polysaccharide-isolated-from-enteromorpha-intestinalis-for-hacking-hepatocellular-carcinoma
#2
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 sulphated 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 non-ionic surfactants (Span 40 and 65)...
November 8, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29054680/phosphorylation-of-protein-phosphatase-2a-facilitated-an-early-stage-of-chemical-carcinogenesis
#3
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...
October 17, 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
#4
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
#5
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
#6
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
#7
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
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
#8
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
#9
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-positive ((+)) 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(+) foci, compared with GST-P(+) foci expressing UBE2E2...
November 1, 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
#10
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
#11
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
#12
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...
October 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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