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Hepatic hypoxia

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https://www.readbyqxmd.com/read/29769640/hypoxia-induced-microrna-191-contributes-to-hepatic-ischemia-reperfusion-injury-through-the-zonab-cyclin-d1-axis
#1
Wenming Pan, Lin Wang, Xiao-Fei Zhang, Hongji Zhang, Jinxiang Zhang, Guoliang Wang, Peng Xu, Yunwei Zhang, Ping Hu, Xiao-Dong Zhang, Run-Lei Du, Hui Wang
Hepatic ischemia/reperfusion injury (IRI) is a common cause of morbidity and mortality in liver transplantation settings and involves severe cell death and inflammatory responses. MicroRNA-191 has recently been reported to be abnormally expressed in hepatocellular carcinoma and other liver diseases in the regulation of important cellular processes. However, little is known about its function and molecular mechanism in IRI. Here, we demonstrate that miR-191 is significantly upregulated in a cultured cell line during hypoxia/reperfusion (H/R) and in liver tissue during IRI in mice...
May 16, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29761172/loss-of-hypoxia-inducible-factor-1%C3%AE-aggravates-%C3%AE-%C3%AE-t-cell-mediated-inflammation-during-acetaminophen-induced-liver-injury
#2
Tomohiro Suzuki, Shoko Minagawa, Takashi Yamazaki, Takatomo Arai, Mai Kanai, Satoko Shinjo, Nobuhito Goda
Acetaminophen (APAP)-induced liver injury is closely associated with acute hepatic inflammation. Hypoxia-inducible factor-1 (HIF-1) is activated during immunological processes and regulates gene expressions in various types of immune cells. Although HIF-1 controls the differentiation and functions of conventional T cells in chronic inflammation, the pathological importance of HIF-1 in innate-like T cells during acute inflammation remains unknown. Here, we investigated the role of HIF-1 in innate-like γδ T cells during APAP-induced acute liver injury...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29746885/curcumin-inhibits-hepatic-stellate-cell-activation-via-suppression-of-succinate-associated-hif-1%C3%AE-induction
#3
Linlin She, Dan Xu, Zixia Wang, Yirui Zhang, Qingli Wei, Jiye Aa, Guangji Wang, Baolin Liu, Yuan Xie
PURPOSE: Aberrant succinate accumulation emerges as a unifying mechanism for inflammation and oxidative stress. This study aims to investigate whether curcumin ameliorates hepatic fibrosis via blocking succinate signaling. METHODS: We investigated the effects of curcumin on hepatic succinate accumulation and liver fibrosis in mice fed a high-fat diet (HFD). Meanwhile, we stimulated mouse primary hepatic stellate cells (HSCs) with succinate and observed the inhibitory effects of curcumin on succinate signaling...
May 7, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29742804/monocyte-chemoattractant-protein-induced-protein-1-targets-hypoxia-inducible-factor-1%C3%AE-to-protect-against-hepatic-ischemia-reperfusion-injury
#4
Peng Sun, Yue-Xin Lu, Daqing Cheng, Kuo Zhang, Jilin Zheng, Yupeng Liu, Xiaozhan Wang, Yu-Feng Yuan, Yi-Da Tang
Sterile inflammation is an essential factor causing hepatic ischemia/reperfusion (I/R) injury. As a critical regulator of inflammation, the role of monocyte chemoattractant protein-induced protein 1 (MCPIP1) in hepatic I/R injury remains undetermined. In this study, we discovered that MCPIP1 downregulation was associated with hepatic I/R injury in liver transplant patients and a mouse model. Hepatocyte-specific Mcpip1 gene knockout (HKO) and transgenic (HTG) mice demonstrated that MCPIP1 functions to ameliorate liver damage, reduce inflammation, prevent cell death, and promote regeneration...
May 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29734133/down-regulation-of-ifit3-protects-liver-from-ischemia-reperfusion-injury
#5
Ge Guan, Yuntai Shen, Qianqian Yu, Huan Liu, Bin Zhang, Yuan Guo, Xiaodan Zhu, Zhiqiang Li, Wei Rao, Likun Zhuang, Yunjin Zang
Hepatic ischemia-reperfusion injury (IRI) could result in severe liver damage and dysfunction during liver surgery and transplantation. As one of the Interferon (IFN)-stimulated genes, IFIT3 exerted antitumor activity but its roles in hepatic IRI are still unknown. In this study, roles of IFIT3 in hepatic IRI were investigated using a mouse hepatic IRI model and a cellular hypoxia-reoxygenation model. Firstly, our results showed that IFIT3 was up-regulated in reperfused liver tissues of patients undergoing liver transplantation and was positively correlated with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)...
May 4, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29724996/wwox-controls-hepatic-hif1%C3%AE-to-suppress-hepatocyte-proliferation-and-neoplasia
#6
Muhannad Abu-Remaileh, Abed Khalaileh, Eli Pikarsky, Rami I Aqeilan
Liver cancer is one of the most lethal malignancies with very poor prognosis once diagnosed. The most common form of liver cancer is hepatocellular carcinoma (HCC). The WW domain-containing oxidoreductase (WWOX) is a large gene that is often perturbed in a wide variety of tumors, including HCC. WWOX has been shown to act as a tumor suppressor modulating cellular metabolism via regulating hypoxia-inducible factor 1α (HIF-1α) levels and function. Given that WWOX is commonly inactivated in HCC, we set to determine whether specific targeted deletion of murine Wwox affects liver biology and HCC development...
May 3, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29722563/damage-associated-molecular-patterns-damps-in-resuscitated-hemorrhagic-shock-are-mitigated-by-peritoneal-fluid-administration
#7
Paul J Matheson, Mark A Eid, Matthew A Wilson, Victoria S Graham, Samuel A Matheson, Jessica Lee Weaver, Cynthia D Downard, Jason W Smith
INTRODUCTION: Conventional resuscitation (CR) of hemorrhagic shock (HS), a significant cause of trauma mortality, is I.V. blood and fluids. CR restores central hemodynamics, but vital organ flow can drop causing hypoperfusion, hypoxia, Damage-Associated Molecular Patterns (DAMPs), and remote organ dysfunction (i.e., lung). CR plus Direct Peritoneal Resuscitation (DPR) prevents intestinal and hepatic hypoperfusion. We hypothesized that DPR prevents lung injury in HS/CR by altering DAMPs...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29712435/prolyl-hydroxylase-inhibitors-a-breakthrough-in-the-therapy-of-anemia-associated-with-chronic-diseases
#8
Amit Arvind Joharapurkar, Vrajesh Bhaskarbhai Pandya, Vishal J Patel, Ranjit C Desai, Mukul R Jain
Chronic kidney disease, cancer, chronic inflammatory disorders, nutritional and genetic deficiency can cause anemia. Hypoxia causes induction of hypoxia-inducible factor (HIF), which stimulates erythropoietin (EPO) synthesis. Prolyl hydroxylase domain (PHD) enzyme inhibition can stabilize hypoxia-inducible factor (HIF). HIF stabilization also decreases hepcidin, a hormone of hepatic origin, which regulates iron homeostasis. PHD inhibitors represent the novel pharmacological treatment of anemia of chronic diseases...
May 1, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29709475/tnip1-alleviates-hepatic-ischemia-reperfusion-injury-via-the-tlr2-myd88-pathway
#9
Yong Zhang, Xiaoming Lei, Wei Li, Xiaoying Ding, Jie Bai, Jin Wang, Gang Wu
Hepatic ischemia/reperfusion (I/R) injury induces oxidative stress, hepatocyte apoptosis, and release of inflammatory cytokines, which together causes liver damage and even organ dysfunction. TNF-α-induced protein 3-interacting protein 1 (TNIP1) reportedly decreases expression of genes associated with stress response and inflammation. Thus, we investigated the effects of TNIP1 on hepatic cells injury caused by hypoxia/reoxygenation (H/R). Reduced expression of TNIP1 was determined in I/R mice compared to normal mice...
April 27, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29701197/-role-of-drug-transporters-in-rational-use-of-drugs-at-high-altitude-area
#10
Wenbin Li, Baohua Yan, Rong Wang, Zhengping Jia
Pharmacokinetics plays a key role in rational use of medicines. Many factors can affect the drug's pharmacokinetics. Previous studies mainly focused on the impact of hypoxia on hepatic drug metabolizing enzyme, but uncommon on drug transporters. Actually, drug transporter is a key factor for activation of the drugs transport across the cell membrane into the inside of cells, such as multidrug resistance protein (MDR), breast cancer resistance protein (BCRP), multidrug resistance associated protein (MRP), organic cation transporter (OCT), organic anion-transporting polypeptide (OATP), organic anion transporter (OAT), qligopeptide transporter (PEPT), etc...
March 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29693586/ellagic-acid-alleviates-hepatic-oxidative-stress-and-insulin-resistance-in-diabetic-female-rats
#11
Simran Alexandria Polce, Cameron Burke, Lucas Martins França, Benjamin Kramer, Antonio Marcus de Andrade Paes, Maria Alicia Carrillo-Sepulveda
Non-alcoholic fatty liver disease (NAFLD) affects more than 70% of patients with type 2 diabetes mellitus (T2DM) and has become one of the most common metabolic liver diseases worldwide. To date, treatments specifically targeting NAFLD do not exist. Oxidative stress and insulin resistance have been implicated in the pathogenesis of NAFLD in diabetes. Accordingly, the goal of this present study was to determine whether Ellagic acid (EA), a natural antioxidant polyphenol found in berries and nuts, mitigates hepatic oxidative stress and insulin resistance in T2DM rats, and thus alleviates NAFLD...
April 25, 2018: Nutrients
https://www.readbyqxmd.com/read/29686697/ppar-%C3%AE-antagonizes-hypoxia-induced-activation-of-hepatic-stellate-cell-through-cross-mediating-pi3k-akt-and-cgmp-pkg-signaling
#12
Qinghui Zhang, Shihao Xiang, Qingqian Liu, Tao Gu, Yongliang Yao, Xiaojie Lu
Background and Aims: Accumulating evidence reveals that PPAR γ plays a unique role in the regulation of hepatic fibrosis and hepatic stellate cells (HSCs) activation. This study was aimed at investigating the role of PPAR γ in hypoxia-induced hepatic fibrogenesis and its possible mechanism. Methods: Rats used for CCl4-induced hepatic fibrosis model were exposed to hypoxia for 8 hours each day. Rats exposed to hypoxia were treated with or without the PPAR γ agonist rosiglitazone...
2018: PPAR Research
https://www.readbyqxmd.com/read/29682743/the-selective-mineralcorticoid-receptor-mr-antagonist-eplerenon-prevents-decompensation-of-liver-cirrhosis
#13
Barbara Schreier, Anja Wolf, Stefanie Hammer, Sabine Pohl, Sigrid Mildenberger, Sindy Rabe, Michael Gekle, Alexander Zipprich
BACKGROUND & AIMS: The MR contributes to fibrosis in various tissues and MR antagonists, like eplerenone, are used to prevent fibrosis. The role of MR antagonists for hepatic fibrosis and cirrhosis is unknown. Here, we investigated the role of MR and eplerenone in cirrhosis development. METHODS: Liver fibrosis (5 weeks), cirrhosis without (8w) and with ascites (12w) were induced by CCl4 in rats and comprehensively analyzed. In addition the effect of eplerenone (MR antagonist) on the development of cirrhosis with ascites was assessed...
April 22, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29678877/deferoxamine-ameliorates-adipocyte-dysfunction-by-modulating-iron-metabolism-in-ob-ob-mice
#14
Hong-Fa Yan, Zhao-Yu Liu, Zhi-Ang Guan, Chuang Guo
OBJECTIVE: The mechanisms underlying obesity and anti-obesity processes have garnered remarkable attention as potential therapeutic targets for obesity-associated metabolic syndromes. Our prior work has shown the healing efficacy of iron reduction therapies for hepatic steatosis in a rodent model of diabetes and obesity. In this study, we investigated how iron depletion by deferoxamine (DFO) affected adipocyte dysfunction in the epididymal adipose tissues of ob/ob mice. METHODS: Male ob/ob mice were assigned to either a vehicle-treated or DFO-treated group...
April 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29643975/physiological-hypoxia-enhances-stemness-preservation-proliferation-and-bidifferentiation-of-induced-hepatic-stem-cells
#15
Xiaosong Zhi, Jun Xiong, Mengchao Wang, Hongxia Zhang, Gang Huang, Jian Zhao, Xiaoyuan Zi, Yi-Ping Hu
Induced hepatic stem cells (iHepSCs) have great potential as donors for liver cell therapy due to their self-renewal and bipotential differentiation properties. However, the efficiency of bidifferentiation and repopulation efficiency of iHepSCs is relatively low. Recent evidence shows that physiological hypoxia, a vital factor within stem cell "niche" microenvironment, plays key roles in regulating tissue stem cell biological behaviors including proliferation and differentiation. In this study, we found that physiological hypoxia (10% O2 ) enhanced the stemness properties and promoted the proliferation ability of iHepSCs by accelerating G1/S transition via p53-p21 signaling pathway...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29607154/decreased-expression-of-hepatic-cytochrome-p450-1a2-cyp1a2-in-a-chronic-intermittent-hypoxia-mouse-model
#16
Xiao-Bin Zhang, Yi-Ming Zeng, Xiao-Yang Chen, Yi-Xiang Zhang, Jin-Zhen Ding, Cheng Xue
Background: Hepatic cytochrome P450 (CYP) isoforms, CYP1A2, is one of important enzymes for many drugs metabolism. Studies have confirmed that sustained hypoxia can influence the expression of hepatic CYP, including CYP1A2. The impact of chronic intermittent hypoxia (CIH), a marked characteristic of sleep apnea, on CYP1A2 remains unclear. The aim of the present study was to evaluate the effect of CIH on the expression of hepatic CYP1A2 in a mouse model with sleep apnea. Methods: Twenty four old male (6-8 weeks) C57BL/6J mice (n=12 in each group) were randomly assigned to either normoxia group or CIH group...
February 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29601782/hepatic-phd2-hif-1%C3%AE-axis-is-involved-in-postexercise-systemic-energy-homeostasis
#17
Beibei Luo, Dao Xiang, Die Wu, Changcheng Liu, Yiqun Fang, Peijie Chen, Yi-Ping Hu
Exercise plays an important role in the prevention and treatment of chronic liver disease and associated metabolic disorders. A single bout of exercise induces tissue blood flow redistribution, which decreases splanchnic circulation and leads to physiologic hypoxia in the gastrointestinal system and liver. The transcription factor, hypoxia inducible factor-1α (HIF-1α), and its regulator, prolylhydroxylase 2 (PHD2), play pivotal roles in the response to oxygen flux by regulating downstream gene expression levels in the liver...
March 30, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29589772/alda-1-an-aldh2-activator-protects-against-hepatic-ischemia-reperfusion-injury-in-rats-via-inhibition-of-oxidative-stress
#18
Tao Zhang, Qiang Zhao, Fang Ye, Chan-Yan Huang, Wan-Mei Chen, Wen-Qi Huang
AIM: Previous studies have proved that activation of aldehyde dehydrogenase two (ALDH2) can attenuate oxidative stress through clearance of cytotoxic aldehydes, and can protect against cardiac, cerebral and lung ischemia/reperfusion (I/R) injuries. In this study, we investigated the effects of the ALDH2 activator Alda-1 on hepatic I/R injury. METHODS: Partial warm ischemia was performed in the left and middle hepatic lobes of Sprague-Dawley rats for 1 h, followed by 6 h of reperfusion...
March 28, 2018: Free Radical Research
https://www.readbyqxmd.com/read/29566343/modulation-of-hepatic-gene-expression-profiles-by-vitamins-b1-b2-and-niacin-supplementation-in-mice-exposed-to-acute-hypoxia
#19
Jin Liu, Weina Gao, Lingling Pu, Jingyu Wei, Zhonghao Xin, Yawen Wang, Tala Shi, Changjiang Guo
This study was aimed to observe the effects of vitamins B1, B2 and niacin supplementation on hepatic gene expression profiles in mice exposed to acute hypoxia. Thirty mice were randomly divided into normal, acute hypoxia, and acute hypoxia plus vitamins B1, B2 and niacin supplementation groups and fed corresponding diets for two weeks and then exposed to a simulated altitude of 6000 meters for 8 hours. Hepatic gene expression profiles were analyzed using a microarray technique. Several biochemical markers were also assayed...
March 22, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29558045/liver-dysfunction-in-sepsis
#20
REVIEW
Ewa A Woźnica, Małgorzata Inglot, Ryszard K Woźnica, Lidia Łysenko
Despite continuous progress in medicine, sepsis remains the main cause of deaths in the intensive care unit. Liver failure complicating sepsis/septic shock has a significant impact on mortality in this group of patients. The pathophysiology of sepsis-associated liver dysfunction is very complicated and still not well understood. According to the Surviving Sepsis Campaign (SSC) Guidelines, the diagnosis of liver dysfunction during sepsis is based on the increase in bilirubin concentration >2 mg/dL and the occurrence of coagulation disorders with INR > 1...
March 20, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
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