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Hepatic injury

Clifford Akateh, Eliza W Beal, Jung-Lye Kim, Brenda F Reader, Katelyn Maynard, Jay L Zweier, Bryan A Whitson, Sylvester M Black
BACKGROUND: Ischemia/reperfusion injury (IRI) can occur during liver surgery. Endogenous catalase is important to cellular antioxidant defenses and is critical to IRI prevention. Pegylation of catalase (PEG-CAT) improves its therapeutic potential by extending plasma half-life, but systemic administration of exogenous PEG-CAT has been only mildly therapeutic for hepatic IRI. Here, we investigated the protective effects of direct intrahepatic delivery of PEG-CAT during IRI using a rat hilar clamp model...
February 13, 2019: Journal of Surgical Research
Yu Guo, Di Xiao, Xiaojing Yang, Jiang Zheng, Shuwei Hu, Panfeng Wu, Xiaoxia Li, Hao Kou, Hui Wang
Hepatic and pulmonary toxicity in fetal rats induced by pyrrolizidine alkaloids (PAs) was investigated. Retrorsine (RTS) or monocrotaline (MCT) was intragastrically administered during pregnancy. The reduction of body and tail lengths was consistent with body weight loss in PA-exposed fetuses, and pathological lesions in liver and lung were observed only in fetuses. Both PAs reduced fetal serum transaminase activities. The GSH/GSSG ratio, GSH peroxidase and superoxide dismutase activities also decreased but glutathione S-transferase activity increased in fetal lung, especially for MCT...
February 13, 2019: Reproductive Toxicology
Ming-Xiang Cheng, Jin-Zheng Li, Yong Chen, Ding Cao, Jian-Ping Gong, Bing Tu
BACKGROUND: Vascular endothelial growth factor receptor-3 (VEGFR-3) / vascular endothelial growth factor -c (VEGF-C) signaling is reported to negatively regulate TLR4-triggered inflammation of macrophages. This study aims to clarify whether the VEGFR-3/VEGF-C signaling can suppress Kupffer cells (KCs) activation and attenuate hepatic ischemia-reperfusion injury (IRI) after liver transplantation. METHODS: A rat model of liver transplantation was performed. Donor livers were perfused with VEGF-C injection via portal vein during cold preservation, and controls were perfused with UW solution...
February 13, 2019: Transplant Immunology
Song Zhang, Shun Guo, Xiao-Bo Gao, An Liu, Wei Jiang, Xi Chen, Peng Yang, Lin-Na Liu, Lei Shi, Yan Zhang
Lipid metabolism disorders lead to vascular endothelial injury. Matrine is an alkaloid that has been used to improve obesity and diabetes and for the treatment of hepatitis B. However, its effect on lipid metabolism disorders and vascular injury is unclear. Here, we investigated the effect of matrine on high-fat diet fed mice and oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs). Computational virtual docking analyses, phosphoinositide 3-kinase (PI3K) and protein kinase C-α (PKCα) inhibitors were used to localize matrine in vascular injuries...
February 15, 2019: Journal of Cellular and Molecular Medicine
Xiang Tao, Yuting Hu, Li Li, Rui Xu, Jing Fu, Qiangsong Tong, Qin Fu
β2 Adrenergic receptors (β2 ARs) are G protein-coupled receptors (GPCRs) that are expressed in major insulin target tissues. β2 ARs play an important role in the regulation of lipid metabolism during aging; however, little is known about the significance of β2 ARs in the pathogenesis of hepatic fat accumulation in high-fat diet (HFD) mice. This study aims to examine the role of β2 AR in the development of nonalcoholic fatty liver disease (NAFLD) induced by HFD and the underlying mechanisms. Surprisingly, we found that genetic deletion of β2 AR significantly increased the liver weight of mice fed a HFD for 20 weeks compared to that of wild-type (WT) mice...
February 12, 2019: Biochemical and Biophysical Research Communications
Phillipp Hartmann, Huikuan Chu, Yi Duan, Bernd Schnabl
The intestinal microbiome plays an major role in the pathogenesis of liver disease, with a hallmark event being dysbiosis, or an imbalance of pathobionts and beneficial bacteria with the associated deleterious effects on its host. Reducing the number of intestinal bacteria with antibiotic treatment is generally advantageous in experimental liver diseases. Complete absence of intestinal microbiota as in germ-free rodents can be protective in autoimmune hepatitis, and hepatic tumors induced by chemicals; or it can exacerbate disease as in acute toxic liver injury and liver fibrosis/cirrhosis...
February 15, 2019: American Journal of Physiology. Gastrointestinal and Liver Physiology
Hao Li, Tian Zhang, Ke Wang, Meng Lu, Yonghong Guo, Ye Zhang, Zhi-Nan Chen, Huijie Bian
Milk fat globule-EGF factor 8 (MFGE8) has been reported to play various roles in acute injury and inflammation response. However, the role of MFGE8 in liver injury is poorly investigated. The present research was designed to clarify the expression and function of MFGE8 in carbon tetrachloride (CCl4 )-induced liver injury. Using serum cytokine arrays, we selected a promising cytokine MFGE8 as the candidate in the process of hepatitis-fibrosis-hepatocellular carcinoma (HCC) progression, based on the elevated expression in both hepatic fibrosis and HCC models...
February 14, 2019: Journal of Cellular Physiology
Takahiro Zenda, Ichiro Araki, Motoko Sasaki
Giant cell hepatitis in adults is considered a rapidly progressive and life-threatening disease, but there are few descriptions of a prolonged disease course. A 36-year-old Japanese man was referred to our hospital for further evaluation of abnormal liver function test results. Although asymptomatic, he had undergone follow-up for 9 years with these abnormalities. Because the cause of liver injury was not identified despite extensive noninvasive examinations, the patient underwent needle biopsy. He was finally diagnosed with post-infantile giant cell hepatitis (PIGCH) based on the presence of small numbers of giant multinucleated hepatocytes scattered primarily around the portal area...
February 14, 2019: Clinical Journal of Gastroenterology
Barbara Ulmasov, Hidenao Noritake, Peter Carmichael, Kiyoko Oshima, David W Griggs, Brent A Neuschwander-Tetri
The presence and stage of liver fibrosis in patients with nonalcoholic steatohepatitis (NASH) is strongly associated with mortality. Thus, both preventing and reversing fibrosis are critically important approaches to prevent death or the need for liver transplantation from NASH. Recently, fibrosis in several mouse models of organ injury was shown to be prevented and reversed with the potent small molecule, arginine-glycine-aspartic acid tripeptide (RGD)-binding, integrin antagonist (3S)-3-(3-bromo-5-(tert-butyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid (Center for World Health and Medicine [CWHM]-12)...
February 2019: Hepatology Communications
Li Chen, David A Brenner, Tatiana Kisseleva
Hepatic fibrosis results from chronic injury and inflammation in the liver and leads to cirrhosis, liver failure, and portal hypertension. Understanding the molecular mechanisms underlying hepatic fibrosis has advanced the prospect of developing therapies for regression of the disease. Resolution of fibrosis requires a reduction of proinflammatory and fibrogenic cytokines, a decrease in extracellular matrix (ECM) protein production, an increase in collagenase activity, and finally, a disappearance of activated myofibroblasts...
February 2019: Hepatology Communications
Priya Grewal, Jawad Ahmad
Purpose of Review-: Without a specific biomarker the diagnosis of drug-induced liver injury (DILI) relies on exclusion of other causes of liver injury. This review examines the importance of testing for hepatitis C (HCV) and hepatitis E (HEV) in patients with suspected DILI. Recent Findings-: Several national DILI registries have reported HCV and HEV infection in patients initially diagnosed with DILI. Particularly in patients with suspected DILI who have acute hepatocellular liver injury, acute HCV and acute HEV infection should be considered even in the absence of traditional risk factors...
September 2018: Current Hepatology Reports
Yuting Yang, Caiyang Chen, Cui Cui, Yingfu Jiao, Peiying Li, Ling Zhu, Weifeng Yu, Qiang Xia, Daxiang Wen, Liqun Yang
Our previous study demonstrated that remifentanil, an opioid agonist, conferred profound liver protection during hepatic ischemia reperfusion injury (HIRI), in which Toll-like receptors (TLRs) played a crucial role in mediating the inflammatory responses. β-arrestin2, a well-known mu opioid receptor desensitizer, is also a negatively regulator of Toll-like receptor 4 (TLR4)-mediated inflammatory reactions in a mitogen-activated protein kinase (MAPK)-dependent manner. Using the rodent models of hepatic ischemia reperfusion injury both in wild type and TLR4 knockout (TLR4 KO) mice, we found that remifentanil preconditioning could inhibit the expression of TLR4 and reduce the inflammatory response induced by HIRI in wild type but not in TLR4 KO mice...
February 14, 2019: Scientific Reports
Qing Zhu, Yong-Yi Zhu, Wei-Ning Wang
High fat diet (HFD)-induced obesity is associated with insulin resistance (IR) and other chronic, diet associated illnesses, including neuroinflammation and brain injury. However, the involvement of inflammatory response in HFD-elicited central nerve injury has yet to be fully determined. Recent studies have indicated that tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein (TRUSS), also known as TRPC4AP, plays an essential role in regulating inflammation via the meditation of NF-κB signaling...
February 11, 2019: Biochemical and Biophysical Research Communications
Jin-Yong Joung, Jung-Hyo Cho, Yun-Hee Kim, Seung-Hoon Choi, Chang-Gue Son
INTRODUCTION: Experimental studies and clinical observations have shown that stress can damage hepatic tissue both directly and indirectly. Many studies have partially revealed the contributors of stress-induced liver injury; however, the whole process has not yet been uncovered. This review aims to summarize the mechanisms that have been proposed to be involved. METHODS: A literature search was conducted using PubMed ( in its entirety up to March 2018, and analyzed the animal-derived mechanistic studies on stress-induced liver injury...
February 13, 2019: Brain and Behavior
Arie Regev, Melissa Palmer, Mark I Avigan, Lara Dimick-Santos, William R Treem, John F Marcinak, Daniel Seekins, Gopal Krishna, Frank A Anania, James W Freston, James H Lewis, Arun J Sanyal, Naga Chalasani
BACKGROUND: The last decade has seen a rapid growth in the number of clinical trials enrolling patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). Due to the underlying chronic liver disease, patients with NASH often require different approaches to the assessment and management of suspected drug-induced liver injury (DILI) compared to patients with healthy livers. However, currently no regulatory guidelines or position papers systematically address best practices pertaining to DILI in NASH clinical trials...
February 13, 2019: Alimentary Pharmacology & Therapeutics
Albert J Czaja
BACKGROUND: Disturbances in iron regulation have been described in diverse chronic liver diseases other than hereditary haemochromatosis, and iron toxicity may worsen liver injury and outcome. AIMS: To describe manifestations and consequences of iron dysregulation in chronic liver diseases apart from hereditary haemochromatosis and to encourage investigations that clarify pathogenic mechanisms, define risk thresholds for iron toxicity, and direct management METHODS: English abstracts were identified in PubMed by multiple search terms...
February 13, 2019: Alimentary Pharmacology & Therapeutics
An-Na Jiang, Song Wang, Wei Yang, Kun Zhao, Xiu-Mei Bai, Zhong-Yi Zhang, Wei Wu, Min-Hua Chen, Kun Yan
PURPOSE: To investigate the role of a novel curved radiofrequency ablation (RFA) electrode with controllable direction in the ablation of tumors behind large hepatic vessels in ex vivo bovine and in vivo canine liver experiments. MATERIALS AND METHODS: Approval from the institutional animal care and use committee was obtained. In ex vivo experiments, conventional multi-tines expandable electrodes, conventional monopolar straight electrodes and novel curved electrodes were used in the ablation of the bovine liver (n = 90)...
February 13, 2019: Cardiovascular and Interventional Radiology
Hwa-Young Lee, Geum-Hwa Lee, Young Yoon, Han-Jung Chae
This study aimed to characterize the protective effects of R. verniciflua extract (ILF-R) and E. ulmoides extract (ILF-E), the combination called ILF-RE, against chronic CCl₄-induced liver oxidative injury in rats, as well as to investigate the mechanism underlying hepatoprotection by ILF-RE against CCl₄-induced hepatic dysfunction. Chronic hepatic stress was induced via intraperitoneal (IP) administration of a mixture of CCl₄ (0.2 mL/100 g body weight) and olive oil [1:1(v/v)] twice a week for 4 weeks to rats...
February 12, 2019: Nutrients
Zhaoyang Hu, Thomas Jepps, Leng Zhou, Jin Liu, Mufeng Li, Geoffrey W Abbott
Activation of anti-apoptotic signaling cascades such as the reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways is protective in a variety of tissues in the context of ischemia reperfusion (IR) injury. Hepatic IR injury causes clinically significant hepatocellular damage in surgical procedures including liver transplantation and hepatic resection, increasing associated morbidity and mortality. We previously found that the cardiovascular-expressed potassium channel ancillary subunit, KCNE4, sex-specifically influences the cardiac RISK/SAFE pathway response to IR, and that Kcne4 deletion testosterone-dependently exacerbates cardiac IR injury...
February 13, 2019: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Carolyn K J Young, Matthew J Young
HepaRG is a proliferative human hepatoma-derived cell line that can be differentiated into hepatocyte-like and biliary-like cells. Differentiated HepaRG cultures maintain key hepatic functions including drug transporters and xenobiotic-metabolizing enzymes. To gain insight into proliferative and differentiated HepaRG metabolism we profiled various bioenergetic parameters and investigated cell culture levels of adenosine triphosphate (ATP), lactate, and lactate dehydrogenase (LDH) activity. Compared to differentiated-derived HepaRG, cells from proliferative cultures had increased basal and ATP-linked respiration and decreased maximal and spare respiratory capacities...
February 12, 2019: Cell Cycle
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