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Hepatic injury

Irina G Danilova, Boris G Yushkov, Irina A Kazakova, Anna V Belousova, Artem S Minin, Musa T Abidov
Pharmacological interventions which could be hepatoprotective, depending on bioavailability, anti-inflammatory and macrophage-targeting potential of drugs, are still at early preclinical stages. Existing evidence from many animal models of liver injury, as well as from human data, indicate that pharmacological and/or phytochemical interventions have limited impact on liver recovery. Recent studies on stem cell therapies focused on different cell subsets involved in tissue repair, including monocytes/macrophages and bone marrow cells migrating to the injured liver...
December 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jun Zheng, Hui Li, Liying He, Yiming Huang, Jianye Cai, Liang Chen, Chaorong Zhou, Hongyuan Fu, Tongyu Lu, Yingcai Zhang, Jia Yao, Yang Yang
OBJECTIVES: Transfusion of umbilical cord-derived mesenchymal stem cells (UC-MSCs) is a novel strategy for treatment of various liver diseases. However, the therapeutic effect of UC-MSCs is limited because only a few UC-MSCs migrate towards the damaged regions. In this study, we observed the effects of autophagy on the migration of UC-MSCs in vitro and in a model of liver ischaemia/reperfusion (I/R) injury. MATERIALS AND METHODS: We investigated the effects of autophagy on the status of the cell, release of anti-inflammatory factors and migration of UC-MSCs in vitro...
December 10, 2018: Cell Proliferation
David J Orlicky, Andrew E Libby, Elise S Bales, Rachel H McMahan, Jenifer Monks, Francisco G La Rosa, James L McManaman
KEY POINTS: Wild type mice as well as mice with hepatocyte-specific or whole-body deletions of perilipin-2 (Plin2) were used to define hepatocyte and extra-hepatocyte effects of altered cellular lipid storage on obesity and non-alcoholic fatty liver disease (NAFLD) pathophysiology in a western-diet (WD) model of these disorders. Extra-hepatocyte actions of Plin2 are responsible for obesity, adipose inflammation, and glucose clearance abnormalities in WD-fed mice. Hepatocyte and extra-hepatic actions of Plin2 mediate fatty liver formation in WD-fed mice through distinct mechanisms...
December 8, 2018: Journal of Physiology
Fatma Farrag Ali, Rehab Ahmed Rifaai
Omega-3 fatty acids are gaining attention as a therapeutic agent of many diseases. Their protective effect in a variety of diseases has been demonstrated. To the best of our knowledge, this is the first study on omega-3 fatty acids related to acute cold-restraint stress (CRS) induced hepatic dysfunction in rats. Forty adult male Sprague-Dawley albino rats were used and classified into: control, omega-3 group, each rat was pretreated with omega-3 fatty acids; CRS group, rats were subjected to acute CRS for 6 hr; and CRS group pretreated with omega-3 fatty acids...
December 7, 2018: Journal of Cellular Physiology
Madeleine Themanns, Florian Koban, Christian Bergmayr, Alicja Chrzan, Wolfgang Strohmaier, Johannes Haybaeck, Michael Freissmuth, Eva Zebedin-Brandl
Sinusoidal obstruction syndrome (SOS) is a major complication after hematopoietic stem cell transplantation and belongs to a group of diseases increasingly identified as transplant-related systemic endothelial disease. Administration of defibrotide affords some protection against SOS, but the effect is modest. Hence, there is unmet medical need justifying the preclinical search for alternative approaches. Prostaglandins exert protective actions on endothelial cells of various vascular beds. Here, we explored the therapeutic potential of the prostacyclin analog treprostinil to prevent SOS...
December 7, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Guangwei Liu, Jiangkai Liu, Linping Pian, Songlin Gui, Baoping Lu
α‑lipoic acid (ALA) is a naturally occurring antioxidant with protective effects against various hepatic injuries. The aim of the present study was to investigate the mechanisms by which ALA protects the liver from carbon tetrachloride (CCl4)‑induced liver cirrhosis. The widely used liver cirrhosis rat model was established via an intraperitoneal injection of 2 mg/kg 50% CCl4, three times/week for 8 weeks. Simultaneously, 50 or 100 mg/kg ALA was orally administrated to the rats every day for 8 weeks...
December 4, 2018: Molecular Medicine Reports
Ying Guo, Rongji Dai, Yulin Deng, Lili Sun, Shiying Meng, Nian Xin
The extract of Belamcanda chinensis (L.) leaves (BCLE) is a traditional Chinese herbal medicine for the treatment of hyperglycemia in Hainan province, South China. In this study, the effects of BCLE on obese diabetes were investigated using the KK-Ay mice. The component F2 of BCLE alleviate hyperglycemia and insulin resistance, as indicated by decreased levels of FBG, AUC, GSP, LDH and insulin. High levels of hepatic G6Pase and PEPCK in KK-Ay mice were markedly attenuated by F2. The inhibitory effect of F2 on GSK-3β and the enhancement effect on liver glycogen demonstrated that F2 could significantly inhibit hepatic gluconeogenesis and glycogen accumulation...
December 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Mary E Rinella, James F Trotter, Manal F Abdelmalek, Angelo H Paredes, Margery A Connelly, Mark J Jaros, Lei Ling, Stephen J Rossi, Alex M DePaoli, Stephen A Harrison
BACKGROUND: NGM282, an engineered analogue of the gut hormone FGF19, improves hepatic steatosis and fibrosis biomarkers in patients with nonalcoholic steatohepatitis (NASH). However, NGM282 increases serum cholesterol levels by inhibiting CYP7A1, which encodes the rate-limiting enzyme in the conversion of cholesterol to bile acids. Here, we investigate whether administration of a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor can manage the cholesterol increase seen in NASH patients treated with NGM282...
December 7, 2018: Journal of Hepatology
Bharati Bhattacharjee, Palash Kumar Pal, Arnab Kumar Ghosh, Sanatan Mishra, Aindrila Chattopadhyay, Debasish Bandyopadhyay
Cadmium (Cd) is one of the most ubiquitous toxic heavy metal in the environment. The present study was conducted to evaluate the protective role of aqueous bark extract of Terminalia arjuna (TA) against Cd induced oxidative damage in hepatic and cardiac tissues as the TA bark extract has folkloric medicinal use in the treatment of various hepatic and cardiac disorders. Male Wistar rats were divided into 4 groups. The control group was treated with normal saline as the vehicle; the second group orally administered with TA (20 mg/kg bw) daily for 15 days; the third group injected with Cd-acetate (0...
December 7, 2018: Food and Chemical Toxicology
Ayman S Mohamed, Shimaa A Sadek, Sarah S Hassanein, Amel M Soliman
BACKGROUND: Sepsis is an inevitable stage of bacterial invasion characterized by the deregulated inflammatory response, resulting in multiorgan dysfunction syndrome. Acute liver injury is a common and serious complication in patients with severe sepsis. The most of conventional antibiotics in managing sepsis are effective, but they are accompanied by undesirable side effects. Therefore, the ongoing study aimed to evaluate the efficacy of echinochrome (Ech) pigment isolated from sea urchins on sepsis-induced liver damage using cecal ligation and puncture (CLP) model...
February 2019: Journal of Surgical Research
A Gautam, Y N Paudel, Saz Abidin, U Bhandari
The current study investigated the role of guggulsterone (GS), a farnesoid X receptor antagonist, in the choline metabolism and its trimethylamine (TMA)/flavin monooxygenases/trimethylamine- N-oxide (TMAO) inhibiting potential in a series of in vitro and in vivo studies as determined by high-performance liquid chromatography (HPLC), mass spectroscopy (MS), and liquid chromatography (LC)-MS techniques. Atherosclerosis (AS) was successfully induced in a group of experimental animals fed with 2% choline diet for 6 weeks...
December 9, 2018: Human & Experimental Toxicology
M Z Mohamed, H M Hafez, M Hassan, M A Ibrahim
Liver is a precious organ to maintain body life. Hepatotoxicity is a worldwide health problem that is still a challenge for research. Although countless pharmaceutical drugs and herbal compounds were screened for their hepatoprotective effects, the death from hepatotoxicity is increasing. Thus, there is continuous necessity of searching for the hepatoprotective effect of commonly used drugs. Accordingly, our aim was to examine a hepatoprotective potential for the antihypertensive drug, verapamil, and searching for new insights underlie its protective mechanism...
December 9, 2018: Human & Experimental Toxicology
Noriko Itaba, Ikuya Noda, Hiroyuki Oka, Yohei Kono, Kaori Okinaka, Tsuyoshi Yokobata, Shizuma Okazaki, Minoru Morimoto, Goshi Shiota
Introduction: We previously reported that transplantation of hepatic cell sheets from human bone marrow-derived mesenchymal stem cells (BM-MSCs) with hexachlorophene, a Wnt/β-catenin signaling inhibitor, ameliorated acute liver injury. In a further previous report, we identified IC-2, a newly synthesized derivative of the Wnt/β-catenin signaling inhibitor ICG-001, as a potent inducer of hepatic differentiation of BM-MSCs. Methods: We manufactured hepatic cell sheets by engineering from human BM-MSCs using the single small molecule IC-2...
December 2018: Regenerative Therapy
Kelsey Uminski, Kamran Kadkhoda, Brett L Houston, Alison Lopez, Lauren J MacKenzie, Robbin Lindsay, Andrew Walkty, John Embil, Ryan Zarychanski
Human Granulocytic Anaplasmosis (HGA) is an infection caused by the intracellular bacterium Anaplasma phagocytophilum . As a tick-borne disease, the public health impact of HGA continues to increase with range expansion of the disease vector. The clinical presentation of HGA is often a non-specific febrile illness. The presence of leukopenia, thrombocytopenia, and mild hepatic injury are frequently noted on laboratory investigations, which can be important diagnostic clues in attaining an appropriate diagnosis...
2018: IDCases
Rauf O Yusuf, Henry O Sawyerr, Adedotun T Adeolu, Lateefat M Habeeb, Tawakalitu T Abolayo
Background: Scavengers, due to the nature of their work, are at risk of various occupational hazards while sorting for materials for recycling and sale. They are exposed to blood borne infections such as hepatitis B virus (HBV) infection from injuries from sharps and contact with discarded materials due to non-compliance with standard precautions. Objective: The present study assessed the prevalence of HBV and compliance with safety precautions among scavengers in Ilorin Metropolis, Kwara State, Nigeria...
September 2018: Journal of health & pollution
Peng Liu, Boyan Tian, Lifei Yang, Xinglong Zheng, Xufeng Zhang, Jianhui Li, Xuemin Liu, Yi Lv, Junxi Xiang
Thrombogenicity is the predominant obstacle to successful implantation of decellularized spleen matrix (DSM). The aim of this study was to construct a transplantable functional bioartificial liver (BAL) with the use of DSM. This was achieved by layer-by-layer (LbL) electrostatic immobilization technique by using poly dimethyl diallyl ammonium chloride (PDADMAC) and heparin. After heparin immobilization, DSM gradually turned from translucent into completely opaque milky white. Toluidine blue staining showed strong positive staining of the entire coated DSM...
November 23, 2018: Biomedical Materials
Yao Tong, Zhuang Yu, Renlingzi Zhang, Xibing Ding, Zhixia Chen, Quan Li
BACKGROUND: Hepatic ischemia-reperfusion injury (IRI) is a common pathological phenomenon, which causes hepatic injury as well as remote organ injuries such as the lung. Several mediators, such as oxidative stress, Ca2+ overload and neutrophil infiltration, have been implied in the pathogenesis of liver and remote organ injuries following reperfusion. WNT1 inducible signaling pathway protein 1 (WISP1) is an extracellular matrix protein that has been associated with the onset of several malignant diseases...
December 6, 2018: BMC Pulmonary Medicine
Zhuo Wang, Ming Yan, Jia'an Li, Jiafu Long, Yan Li, Hongmin Zhang
Hepatocellular carcinoma (HCC) is a long-term consequence of chronic inflammatory liver injury. Hepatic injury is associated with a defective intestinal barrier and increased hepatic exposure to bacterial products including lipopolysaccharide (LPS), which promotes hepatocarcinogenesis. Despite its clinical significance, the molecular mediator linking chronic inflammation with HCC development remains to be clarified. In this study, we explored the significant dual functions of active signal transducer and activator of transcription 3 (STAT3) in LPS-induced angiogenesis of HCC...
December 3, 2018: Biochimica et biophysica acta. Molecular cell research
Shinji Furuya, Joseph A Cichocki, Kranti Konganti, Kostiantyn Dreval, Takeki Uehara, Yuuki Katou, Hisataka Fukushima, Hiroshi Kono, Igor P Pogribny, Josepmaria Argemi, Ramon Bataller, Ivan Rusyn
Human alcoholic hepatitis (AH) carries a high mortality rate. AH is an acute-on-chronic form of liver injury characterized by hepatic steatosis, ballooned hepatocytes, neutrophil infiltration, and pericellular fibrosis. We aimed to study the pathogenesis of AH in an animal model which combines chronic hepatic fibrosis with intragastric alcohol administration. Adult male C57BL6/J mice were treated with CCl4 (0.2 ml/kg, 2×weekly by intraperitoneal injections for 6 weeks) to induce chronic liver fibrosis. Then, ethyl alcohol (up to 25 g/kg/day for 3 weeks) was administered continuously to mice via a gastric feeding tube, with or without one-half dose of CCl4...
December 4, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Lecticia Barbosa Jorge, Fernanda Oliveira Coelho, Talita Rojas Sanches, Denise M A C Malheiros, Leandro Ezaquiel de Souza, Fernando Dos Santos, Larissa de Sá Lima, Cristóforo Scavone, Maria Claudia Irigoyen, Makoto Kuro-O, Lucia Andrade
Sepsis-induced organ failure is characterized by a massive inflammatory response and oxidative stress. Acute kidney injury (AKI) occurs in approximately half of patients in septic shock, and the mortality associated with sepsis-induced AKI is unacceptably high. Klotho is a protein expressed by renal cells and has anti-senescence properties. Klotho has also been shown to protect the kidneys in ischemia-reperfusion injury and to have antioxidant properties. To analyze the role of Klotho in sepsis-related organ dysfunction and AKI, we used a cecal ligation and puncture (CLP) model of sepsis in heterozygous Klotho-haploinsufficient mice and their wild-type littermates (CLP-Kl+/- and CLP-WT mice, respectively)...
December 5, 2018: American Journal of Physiology. Renal Physiology
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