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https://www.readbyqxmd.com/read/28196290/curcumin-protects-against-intestinal-origin-endotoxemia-in-rat-liver-cirrhosis-by-targeting-pcsk9
#1
Yu Cai, Di Lu, Yanting Zou, Chaohui Zhou, Hongchun Liu, Chuantao Tu, Feng Li, Lili Liu, Shuncai Zhang
Intestinal origin endotoxemia always occurs in severe liver injury. The aim of the current study was to test antiendotoxemia effect of curcumin on tetrachloride (CCl4 )-induced liver cirrhosis rats, and to elucidate the underlying molecular mechanism. Rat cirrhosis models were constructed with CCl4 subcutaneous injections with curcumin (200 mg/kg/d) administered via gavages for 12 wk until the rats were sacrificed. We found that the administration of curcumin improved the physiological condition pertaining to activity index and temperature, and ameliorated the liver injury in CCl4 -induced cirrhosis rats...
February 14, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28187366/a-combination-of-dietary-n-3-fatty-acids-and-a-cyclooxygenase-1-inhibitor-attenuates-nonalcoholic-fatty-liver-disease-in-mice
#2
Viswanathan Saraswathi, Curtis Perriotte-Olson, Murali Ganesan, Cyrus V Desouza, Yazen Alnouti, Michael J Duryee, Geoffrey M Thiele, Tara M Nordgren, Dahn L Clemens
We sought to determine whether a combination of purified n-3 fatty acids (n-3) and SC-560 (SC), a cyclooxygenase-1-specific inhibitor, is effective in ameliorating nonalcoholic fatty liver disease in obesity. Female wild-type mice were fed a high-fat and high-cholesterol diet (HF) supplemented with n-3 in the presence or absence of SC. Mice treated with SC alone exhibited no change in liver lipids, whereas n-3-fed mice tended to have lower hepatic lipids. Mice given n-3+SC had significantly lower liver lipids compared with HF controls indicating enhanced lipid clearance...
January 27, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28171849/dose-responsive-efficacy-of-umbelliferone-on-lipid-peroxidation-anti-oxidant-and-xenobiotic-metabolism-in-dmba-induced-oral-carcinogenesis
#3
Annamalai Vijayalakshmi, Ganapathy Sindhu
This study evaluated the chemopreventive potential of umbelliferone (UMB) on 7,12- dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis. The mechanistic pathway for chemopreventive potential of UMB was evaluated by measuring the status of tumour incidence, tumour volume, and tumour burden as well as by analyzing the status of phase I, phase II detoxification agents, lipid peroxidation, antioxidants, histopathological changes and also expression patterns of cell proliferation (PCNA, Cyclin D1) and apoptotic (p53) markers using immunohistochemistry in DMBA induced hamster buccal pouch carcinogenesis...
February 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28170202/autologous-neohep-derived-from-chronic-hepatitis-b-virus-patients-blood-monocytes-by-upregulation-of-c-met-signaling
#4
Jashdeep Bhattacharjee, Barun Das, Disha Sharma, Preeti Sahay, Kshama Jain, Alaknanda Mishra, Srikanth Iyer, Puja Nagpal, Vinod Scaria, Perumal Nagarajan, Prakash Khanduri, Asok Mukhopadhyay, Pramod Upadhyay
In view of the escalating need for autologous cell-based therapy for treatment of liver diseases, a novel candidate has been explored in the present study. The monocytes isolated from hepatitis B surface antigen (HBsAg) nucleic acid test (NAT)-positive (HNP) blood were differentiated to hepatocyte-like cells (NeoHep) in vitro by a two-step culture procedure. The excess neutrophils present in HNP blood were removed before setting up the culture. In the first step of culture, apoptotic cells were depleted and genes involved in hypoxia were induced, which was followed by the upregulation of genes involved in the c-MET signaling pathway in the second step...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28170108/caspase-cleaved-k18-fragments-increase-during-alcohol-withdrawal-and-predict-liver-related-death-in-patients-with-ald
#5
S Mueller, P Nahon, V Rausch, T Peccerella, I Silva, E Yagmur, B K Straub, C Lackner, H K Seitz, P Rufat, A Sutton, H Bantel, T Longerich
Non-invasive assessment of disease activity in patients with non-alcoholic (NALFD) and alcoholic liver disease (ALD) is still unsettled but essential for the evaluation of disease progression. We here studied the association of total (M65) and caspase-cleaved (M30) serum keratin-18 fragments (n=204) with histological parameters (n=106) in heavy drinkers primarily admitted for alcohol withdrawal before and after alcohol detoxification. An age, gender and fibrosis-stage matched NAFLD cohort (n=30) was used for comparison...
February 7, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28167773/intestinal-ncor1-a-regulator-of-epithelial-cell-maturation-controls-neonatal-hyperbilirubinemia
#6
Shujuan Chen, Wenqi Lu, Mei-Fei Yueh, Eva Rettenmeier, Miao Liu, Johan Auwerx, Ruth T Yu, Ronald M Evans, Kepeng Wang, Michael Karin, Robert H Tukey
Severe neonatal hyperbilirubinemia (SNH) and the onset of bilirubin encephalopathy and kernicterus result in part from delayed expression of UDP-glucuronosyltransferase 1A1 (UGT1A1) and the inability to metabolize bilirubin. Although there is a good understanding of the early events after birth that lead to the rapid increase in serum bilirubin, the events that control delayed expression of UGT1A1 during development remain a mystery. Humanized UGT1 (hUGT1) mice develop SNH spontaneously, which is linked to repression of both liver and intestinal UGT1A1...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28166653/oxidative-stress-and-inflammation-liver-responses-and-adaptations-to-acute-and-regular-exercise
#7
Rômulo Pillon Barcelos, Luiz Fernando Freire Royes, Javier Gonzalez-Gallego, Guilherme Bresciani
The liver is remarkably important during exercise outcomes due to its contribution to detoxification, synthesis and release of biomolecules, and energy supply to the exercising muscles. Recently, liver has been also shown to play an important role in redox status and inflammatory modulation during exercise. However, while several studies have described the adaptations of skeletal muscles to acute and chronic exercise, hepatic changes are still scarcely investigated. Indeed, acute intense exercise challenges the liver with increased reactive oxygen species (ROS) and inflammation onset, whereas regular training induces hepatic antioxidant and anti-inflammatory improvements...
February 6, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28166367/liver-injury-and-endotoxemia-in-male-and-female-alcohol-dependent-individuals-admitted-to-an-alcohol-treatment-program
#8
Irina A Kirpich, Craig J McClain, Vatsalya Vatsalya, Melanie Schwandt, Monte Phillips, K Cameron Falkner, Lucy Zhang, Catey Harwell, David T George, John C Umhau
BACKGROUND: Interactions between the liver, the gut, and the immune system are critical components of alcoholic liver disease (ALD). The aim of this study was to explore the associations between alcohol-induced liver injury, endotoxemia, and inflammation at admission and over time during abstinence, as well as to examine the sex-related differences in these parameters in alcohol-dependent individuals admitted to an alcohol treatment program. METHODS: A cohort of 48 otherwise healthy participants with alcohol use disorder, but no clinical signs of alcoholic liver injury (34 males (M)/14 females (F)) admitted to an alcohol detoxification program, was stratified into two groups based on baseline plasma alanine aminotransferase (ALT) levels (as a marker of liver injury)...
February 6, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28163821/the-role-of-cyp2e1-in-the-drug-metabolism-or-bioactivation-in-the-brain
#9
REVIEW
W A García-Suástegui, L A Ramos-Chávez, M Rubio-Osornio, M Calvillo-Velasco, J A Atzin-Méndez, J Guevara, D Silva-Adaya
Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28153386/structure-and-biochemistry-of-phenylacetaldehyde-dehydrogenase-from-the-pseudomonas-putida-s12-styrene-catabolic-pathway
#10
Anders G Crabo, Baljit Singh, Tim Nguyen, Shahram Emami, George T Gassner, Matthew H Sazinsky
Phenylacetaldehyde dehydrogenase catalyzes the NAD(+)-dependent oxidation of phenylactealdehyde to phenylacetic acid in the styrene catabolic and detoxification pathway of Pseudomonas putida (S12). Here we report the structure and mechanistic properties of the N-terminally histidine-tagged enzyme, NPADH. The 2.83 Å X-ray crystal structure is similar in fold to sheep liver cytosolic aldehyde dehydrogenase (ALDH1), but has unique set of intersubunit interactions and active site tunnel for substrate entrance...
January 30, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28140328/impact-of-dietary-fibers-on-nutrient-management-and-detoxification-organs-gut-liver-and-kidneys
#11
REVIEW
Dorothy A Kieffer, Roy J Martin, Sean H Adams
Increased dietary fiber (DF) intake elicits a wide range of physiologic effects, not just locally in the gut, but systemically. DFs can greatly alter the gut milieu by affecting the gut microbiome, which in turn influences the gut barrier, gastrointestinal immune and endocrine responses, and nitrogen cycling and microbial metabolism. These gut-associated changes can then alter the physiology and biochemistry of the body's other main nutrient management and detoxification organs, the liver and kidneys. The molecular mechanisms by which DF alters the physiology of the gut, liver, and kidneys is likely through gut-localized events (i...
November 2016: Advances in Nutrition
https://www.readbyqxmd.com/read/28130067/farnesoid-x-receptor-activation-promotes-hepatic-amino-acid-catabolism-and-ammonium-clearance-in-mice
#12
Vittoria Massafra, Alexandra Milona, Harmjan R Vos, Rúben J J Ramos, Johan Gerrits, Ellen C L Willemsen, José M Ramos Pittol, Noortje Ijssennagger, Martin Houweling, Hubertus C M T Prinsen, Nanda M Verhoeven-Duif, Boudewijn M Burgering, Saskia W C van Mil
BACKGROUND & AIMS: The nuclear receptor subfamily 1 group H member 4 (NR1H4 or farnesoid X receptor, FXR) regulates bile acid synthesis, transport, and catabolism. FXR also regulates post-prandial lipid and glucose metabolism. We performed quantitative proteomic analyses of liver tissues from mice to evaluate these functions and investigate whether FXR regulates amino acid metabolism. METHODS: To study the role of FXR in mouse liver, we used mice with a disruption of Nr1h4 (FXR-knockout mice) and compared them to floxed control mice...
January 24, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28129335/reduction-of-aflatoxin-b1-toxicity-by-lactobacillus-plantarum-c88-a-potential-probiotic-strain-isolated-from-chinese-traditional-fermented-food-tofu
#13
Li Huang, Cuicui Duan, Yujuan Zhao, Lei Gao, Chunhua Niu, Jingbo Xu, Shengyu Li
In this study, we investigated the potential of Lactobacillus plantarum isolated from Chinese traditional fermented foods to reduce the toxicity of aflatoxin B1 (AFB1), and its subsequent detoxification mechanism. Among all the investigated L. plantarum strains, L. plantarum C88 showed the strongest AFB1 binding capacity in vitro, and was orally administered to mice with liver oxidative damage induced by AFB1. In the therapy groups, the mice that received L. plantarum C88, especially heat-killed L. plantarum C88, after a single dose of AFB1 exposure, showed an increase in unabsorbed AFB1 in the feces...
2017: PloS One
https://www.readbyqxmd.com/read/28123100/hepatic-detoxification-of-bisphenol-a-is-retinoid-dependent
#14
Igor O Shmarakov, Vira L Borschovetska, William S Blaner
Bisphenol A (BPA, 2,2-bis(4-hydroxyphenyl) propane) is a widely used industrial chemical. The extensive distribution of BPA in the environment poses risks to humans however the molecular mechanisms underlying BPA toxicity as well as its effective detoxification and elimination are not well understood. We have investigated specifically for BPA the notion raised in the literature that the optimal sensing, detoxification and elimination of xenobiotics requires retinoid (natural derivatives and synthetic analogs of vitamin A) actions...
January 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28111842/detoxification-of-benzo-a-pyrene-primarily-depends-on-cytochrome-p450-while-bioactivation-involves-additional-oxidoreductases-including-5-lipoxygenase-cyclooxygenase-and-aldo-keto-reductase-in-the-liver
#15
Liupeng Wang, Wenwei Xu, Leilei Ma, Suxing Zhang, Kezhi Zhang, Peizhen Ye, Guozhen Xing, Xuefeng Zhang, Yiyi Cao, Jing Xi, Jun Gu, Yang Luan
Cytochrome P450s are involved in detoxification and activation of benzo[a]pyrene (BaP) with unclear balance and unknown contribution of other oxidoreductases. Here, we investigated the BaP and BaP-induced mutagenicity in hepatic and extra-hepatic tissues using hepatic P450 reductase null (HRN) gpt mice. After 2-week treatment (50 mg/kg, i.p. 4 days), BaP in the liver and lung of HRN-gpt mice were increased. BaP promoted gpt mutant frequency (MF) in HRN-gpt mice liver. MF of gpt in the lung and Pig-a in hematopoietic cells induced by BaP in HRN-gpt mice were increased than in gpt mice...
January 23, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28069987/transgenic-zebrafish-reporter-lines-as-alternative-in-vivo-organ-toxicity-models
#16
Kar Lai Poon, Xingang Wang, Serene Gp Lee, Ashley S Ng, Wei Huang Goh, Zhonghua Zhao, Muthafar Al-Haddawi, Haishan Wang, Sinnakaruppan Mathavan, Phillip W Ingham, Claudia Mcginnis, Tom J Carney
Organ toxicity, particularly liver toxicity, remains one of the major reasons for termination of drug candidates in the development pipeline as well as withdrawal or restrictions of marketed drugs. A screening-amenable alternative in vivo model such as zebrafish would therefore find immediate application in the early prediction of unacceptable organ toxicity. To identify highly upregulated genes as biomarkers of toxic responses in the zebrafish model, a set of well-characterized reference drugs that cause drug induced liver injury (DILI) in the clinic were applied to zebrafish larvae and adults...
January 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28050235/primary-liver-injury-and-delayed-resolution-of-liver-stiffness-after-alcohol-detoxification-in-heavy-drinkers-with-the-pnpla3-variant-i148m
#17
Vanessa Rausch, Teresa Peccerella, Carolin Lackner, Eray Yagmur, Helmut-Karl Seitz, Thomas Longerich, Sebastian Mueller
AIM: To investigate the influence of PNPLA3 genotype in heavy drinkers on serum markers and liver stiffness (LS) during alcohol withdrawal and its association with histology. METHODS: Caucasian heavy drinkers (n = 521) with a mean alcohol consumption of 192.1 g/d (median alcohol consumption: 169.0 g/d; 95%CI: 179.0-203.3) were enrolled at the Salem Medical Center, University of Heidelberg. LS was measured by transient elastography (Fibroscan, Echosens SA, Paris, France)...
December 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/28031015/melatonin-pharmacology-functions-and-therapeutic-benefits
#18
Sylvie Tordjman, Sylvie Chokron, Richard Delorme, Annaëlle Charrier, Eric Bellissant, Nemat Jaafari, Claire Fougerou
Melatonin synchronizes central but also peripheral oscillators (fetal adrenal gland, pancreas, liver, kidney, heart, lung, fat, gut, etc.), allowing temporal organization of biological functions through circadian rhythms in relation to periodic environmental changes and therefore adaptation of the individual to his/her internal and external environment. Measures of melatonin are considered the best peripheral indices of human circadian timing. First, the pharmacology of melatonin (biosynthesis and circadian rhythms, pharmacokinetics and mechanisms of action) is described, allowing a better understanding of the short and long term effects of melatonin following its immediate or prolonged release...
December 28, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/28026023/effects-of-long-term-ethanol-consumption-and-aldh1b1-depletion-on-intestinal-tumourigenesis-in-mice
#19
Mike F Müller, Ying Zhou, David J Adams, Mark J Arends
Ethanol and its metabolite acetaldehyde have been classified as carcinogens for the upper aerodigestive tract, liver, breast and colorectum. Whereas mechanisms related to oxidative stress and Cyp2e1 induction seem to prevail in the liver, and acetaldehyde has been proposed to play a crucial role in the upper aerodigestive tract, pathological mechanisms in the colorectum have not yet been clarified. Moreover, all evidence for a pro-carcinogenic role of ethanol in colorectal cancer is derived from correlations observed in epidemiological studies or from rodent studies with additional carcinogen application or tumour suppressor gene inactivation...
December 27, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27996102/current-sights-for-mechanisms-of-deoxynivalenol-induced-hepatotoxicity-and-prospective-views-for-future-scientific-research-a-mini-review
#20
REVIEW
Zhao Peng, Liangkai Chen, Andreas K Nüssler, Liegang Liu, Wei Yang
Deoxynivalenol (DON) belongs to the group B trichothecenes, which are the most common mycotoxins in cereal commodities. It is very stable within the temperature range 170-350 °C, showing no reduction in its concentration after 30 min at 170 °C. This chemical property is a very dangerous factor for human and animal health. Liver is also responsible for the detoxification and formation of DON-glucuronide in both human and animals. Some studies already demonstrated that DON could induce liver damage remarkably through DON altering expressions of p53, caspase-3, caspase-7, caspase-8 and Bax in different cell lines...
December 20, 2016: Journal of Applied Toxicology: JAT
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