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https://www.readbyqxmd.com/read/28545313/effects-of-rosmarinic-acid-on-acetaminophen-induced-hepatotoxicity-in-male-wistar-rats
#1
Parisa Hasanein, Maryam Sharifi
CONTEXT: Drug-induced liver injury is a significant worldwide clinical problem. Rosmarinic acid (RA), a natural phenol, has antioxidant effects. OBJECTIVE: The effects of RA against acetaminophen (N-acetyl-p-amino-phenol (APAP))-induced oxidative damage and hepatotoxicity in rats were investigated. MATERIALS AND METHODS: Male Wistar rats were pretreated with RA (10, 50 and 100 mg/kg, i.g.) for one week. On day 7, rats received APAP (500 mg/kg, i...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28545106/serum-microrna-signatures-as-liquid-biopsies-for-interrogating-hepatotoxic-mechanisms-and-liver-pathogenesis-in-human
#2
Julian Krauskopf, Theo M de Kok, Shelli J Schomaker, Mark Gosink, Deborah A Burt, Patricia Chandler, Roscoe L Warner, Kent J Johnson, Florian Caiment, Jos C Kleinjans, Jiri Aubrecht
MicroRNAs (miRNAs) released into the peripheral circulation upon cellular injury have shown a promise as a new class of tissue-specific biomarkers. We were first to demonstrate that next-generation sequencing analysis of serum from human subjects with acetaminophen-induced liver injury revealed a specific signature of circulating miRNAs. We consequently hypothesized that different types of hepatic liver impairments might feature distinct signatures of circulating miRNAs and that this approach might be useful as minimally invasive diagnostic "liquid biopsies" enabling the interrogation of underlying molecular mechanisms of injury in distant tissues...
2017: PloS One
https://www.readbyqxmd.com/read/28543100/syndecan-1-limits-the-progression-of-liver-injury-and-promotes-liver-repair-in-acetaminophen-induced-liver-injury
#3
Eon Jeong Nam, Kazutaka Hayashida, Rafael S Aquino, John R Couchman, Rosemary A Kozar, Jian Liu, Pyong Woo Park
Accidental or intentional misuse of acetaminophen (APAP) is the leading cause of acute liver failure in the Western world. While mechanisms that trigger APAP-induced liver injury are well known, those that halt the progression of APAP liver disease and facilitate liver recovery are less understood. Heparan sulfate proteoglycans (HSPGs) bind to and regulate various tissue injury factors through their heparan sulfate (HS) chains, but the importance of HSPGs in liver injury in vivo remains unknown. Here, we examined the role of syndecan-1, the major cell surface HSPG of hepatocytes, in APAP-induced liver injury...
May 22, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28524081/protective-effects-of-tormentic-acid-a-major-component-of-suspension-cultures-of-eriobotrya-japonica-cells-on-acetaminophen-induced-hepatotoxicity-in-mice
#4
Wen-Ping Jiang, Shyh-Shyun Huang, Yoshikazu Matsuda, Hiroshi Saito, Naoto Uramaru, Hui-Ya Ho, Jin-Bin Wu, Guan-Jhong Huang
An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration. Pretreatment with TA prevented the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), triacylglycerol (TG), and liver lipid peroxide levels in APAP-treated mice and markedly reduced APAP-induced histological alterations in liver tissues...
May 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28521788/methanol-extract-of-dicranopteris-linearis-l-leaves-impedes-acetaminophen-induced-liver-intoxication-partly-by-enhancing-the-endogenous-antioxidant-system
#5
Zainul Amiruddin Zakaria, Farah Hidayah Kamisan, Maizatul Hasyima Omar, Nur Diyana Mahmood, Fezah Othman, Siti Selina Abdul Hamid, Muhammad Nazrul Hakim Abdullah
BACKGROUND: The present study investigated the potential of methanolic extract of Dicranopteris linearis (MEDL) leaves to attenuate liver intoxication induced by acetaminophen (APAP) in rats. METHODS: A group of mice (n = 5) treated orally with a single dose (5000 mg/kg) of MEDL was first subjected to the acute toxicity study using the OECD 420 model. In the hepatoprotective study, six groups of rats (n = 6) were used and each received as follows: Group 1 (normal control; pretreated with 10% DMSO (extract's vehicle) followed by treatment with 10% DMSO (hepatotoxin's vehicle) (10% DMSO +10% DMSO)), Group 2 (hepatotoxic control; 10% DMSO +3 g/kg APAP (hepatotoxin)), Group 3 (positive control; 200 mg/kg silymarin +3 g/kg APAP), Group 4 (50 mg/kg MEDL +3 g/kg APAP), Group 5 (250 mg/kg MEDL +3 g/kg APAP) or Group 6 (500 mg/kg MEDL +3 g/kg APAP)...
May 18, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28507720/in-vivo-imaging-of-leucine-aminopeptidase-activity-in-drug-induced-liver-injury-and-liver-cancer-via-a-near-infrared-fluorescent-probe
#6
Xinyuan He, Lihong Li, Yu Fang, Wen Shi, Xiaohua Li, Huimin Ma
The liver, a main detoxification organ, has evolved a complex enzymatic system to respond to multiple pathological conditions, in which leucine aminopeptidase (LAP) has been reported to participate in detoxifying cisplatin in hepatoma cells and contribute to the intrinsic drug resistance. In vivo imaging of LAP activity in liver disease models is thus helpful to further understand the function of LAP in detoxification and medicine, but such an imaging approach is still lacking. Herein, we develop a selective and sensitive near-infrared fluorescent probe (HCAL) for this purpose...
May 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28504245/macrophage-derived-il-1%C3%AE-promotes-sterile-inflammation-in-a-mouse-model-of-acetaminophen-hepatotoxicity
#7
Chao Zhang, Jin Feng, Jun Du, Zhiyong Zhuo, Shuo Yang, Weihong Zhang, Weihong Wang, Shengyuan Zhang, Yoichiro Iwakura, Guangxun Meng, Yang-Xin Fu, Baidong Hou, Hong Tang
The metabolic intermediate of acetaminophen (APAP) can cause severe hepatocyte necrosis, which triggers aberrant immune activation of liver non-parenchymal cells (NPC). Overzealous hepatic inflammation determines the morbidity and mortality of APAP-induced liver injury (AILI). Interleukin-1 receptor (IL-1R) signaling has been shown to play a critical role in various inflammatory conditions, but its precise role and underlying mechanism in AILI remain debatable. Herein, we show that NLRP3 inflammasome activation of IL-1β is dispensable to AILI, whereas IL-1α, the other ligand of IL-1R1, accounts for hepatic injury by a lethal dose of APAP...
May 15, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28503408/trifluoperazine-inhibits-acetaminophen-induced-hepatotoxicity-and-hepatic-reactive-nitrogen-formation-in-mice-and-in-freshly-isolated-hepatocytes
#8
Sudip Banerjee, Stepan B Melnyk, Kimberly J Krager, Nukhet Aykin-Burns, Sandra S McCullough, Laura P James, Jack A Hinson
The hepatotoxicity of acetaminophen (APAP) occurs by initial metabolism to N-acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts. Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric oxide (NO) and superoxide leading to 3-nitrotyrosine in proteins. Toxicity occurs with inhibited mitochondrial function. We previously reported that in hepatocytes the nNOS (NOS1) inhibitor NANT inhibited APAP toxicity, reactive nitrogen and oxygen species formation, and mitochondrial dysfunction...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28501483/reversal-of-bioenergetics-dysfunction-by-diphenyl-diselenide-is-critical-to-protection-against-the-acetaminophen-induced-acute-liver-failure
#9
Nélson R Carvalho, Cintia C Tassi, Fernando Dobraschinski, Guilherme P Amaral, Ana P Zemolin, Ronaldo M Golombieski, Cristiane L Dalla Corte, Jeferson L Franco, José L Mauriz, Javier González-Gallego, Félix A Soares
Physiopathological conditions such as acute liver failure (ALF) induced by acetaminophen (APAP) can often impair the mitochondrial bioenergetics. Diphenyl diselenide [(PhSe)2] has been shown protects against APAP-induced ALF. The present study aimed to clarify the signaling mechanism involved in the protection of bioenergetics dysfunction associated with ALF-induced by APAP overdose. Mice received APAP (600mg/kg) or (PhSe)2 (15.6mg/kg) alone, or APAP+(PhSe)2, all the solutions were administered by the intraperitoneal (i...
May 10, 2017: Life Sciences
https://www.readbyqxmd.com/read/28501198/introducing-plasma-serum-glycodepletion-for-the-targeted-proteomics-analysis-of-cytolysis-biomarkers
#10
Pauline Maes, Sandrine Donadio-Andréi, Mathilde Louwagie, Yohann Couté, Guillaume Picard, Claire Lacoste, Christophe Bruley, Jérôme Garin, Philippe Ichai, Jamila Faivre, Michel Jaquinod, Virginie Brun
A major class of clinical biomarkers is constituted of intracellular proteins which are leaking into the blood following ischemia, exposure to toxic xenobiotics or mechanical aggression. Their ectopic presence in plasma/serum is an indicator of tissue damage and raises a warning signal. These proteins, referred to as cytolysis biomarkers, are generally of cytoplasmic origin and as such, are devoid of glycosylation. In contrast, most plasma/serum proteins originate from the hepatic secretory pathway and are heavily glycosylated (at the exception of albumin)...
August 1, 2017: Talanta
https://www.readbyqxmd.com/read/28486401/drug-induced-liver-injury-cascade-of-events-leading-to-cell-death-apoptosis-or-necrosis
#11
REVIEW
Andrea Iorga, Lily Dara, Neil Kaplowitz
Drug-induced liver injury (DILI) can broadly be divided into predictable and dose dependent such as acetaminophen (APAP) and unpredictable or idiosyncratic DILI (IDILI). Liver injury from drug hepatotoxicity (whether idiosyncratic or predictable) results in hepatocyte cell death and inflammation. The cascade of events leading to DILI and the cell death subroutine (apoptosis or necrosis) of the cell depend largely on the culprit drug. Direct toxins to hepatocytes likely induce oxidative organelle stress (such as endoplasmic reticulum (ER) and mitochondrial stress) leading to necrosis or apoptosis, while cell death in idiosyncratic DILI (IDILI) is usually the result of engagement of the innate and adaptive immune system (likely apoptotic), involving death receptors (DR)...
May 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28486212/anti-oxidative-and-anti-inflammatory-benefits-of-the-ribonucleoside-analogue-5-azacitidine-in-mice-with-acetaminophen-induced-toxic-hepatitis
#12
Changming Yang, Jun Yi, Xianqiong Gong, Pu Ge, Jie Dai, Ling Lin, Yu Xing, Li Zhang
Toxic hepatitis induced by overdose of acetaminophen (APAP) is one of the major life-threatening problems, oxidative stress and inflammatory injury are the essential underlying mechanisms. 5-Azacytidine (5-AZA) is a ribonucleoside analogue which has been approved for the treatment of patients with acute myeloid leukemia and myelodyplastic syndrome, but recent studies also found that 5-AZA might have anti-oxidative and anti-inflammatory benefits in non-tumor disorders. In the present study, the potential effects of 5-AZA on APAP-induced toxic hepatitis were investigated in a mouse model in vivo...
May 6, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28481086/nontargeted-identification-of-reactive-metabolite-protein-adducts
#13
Michael G Leeming, William A Donald, Richard A J O'Hair
Metabolic bioactivation of many different chemicals results in the formation of highly reactive compounds (chemically reactive metabolites, CRMs) that can lead to toxicity via binding to macromolecular targets (e.g., proteins or DNA). There is a need to develop robust, rapid, and nontargeted analytical techniques to determine the identity of the protein targets of CRMs and their sites of modification. Here, we introduce a nontargeted methodology capable of determining both the identity of a CRM formed from an administered compound as well as the protein targets modified by the reactive metabolite in a single experiment without prior information...
May 16, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28476500/maintenance-of-high-quality-rat-precision-cut-liver-slices-during-culture-to-study-hepatotoxic-responses-acetaminophen-as-a-model-compound
#14
Anne Granitzny, Jan Knebel, Dirk Schaudien, Armin Braun, Pablo Steinberg, Clemens Dasenbrock, Tanja Hansen
Precision cut liver slices (PCLiS) represent a promising tool in reflecting hepatotoxic responses. However, the culture of PCLiS varies considerably between laboratories, which can affect the performance of the liver slices and thus the experimental outcome. In this study, we describe an easily accessible culture method, which ensures optimal slice viability and functionality, in order to set the basis for reproducible and comparable PCLiS studies. The quality of the incubated rat PCLiS was assessed during a 24h culture period using ten readouts, which covered viability (lactate dehydrogenase-, aspartate transaminase- and glutamate dehydrogenase-leakage, ATP content) and functionality parameters (urea, albumin production) as well as histomorphology and other descriptive characteristics (protein content, wet weight, slice thickness)...
May 2, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28464519/the-haptoglobin-beta-subunit-sequesters-hmgb1-toxicity-in-sterile-and-infectious-inflammation
#15
Huan Yang, Haichao Wang, Yongjun Wang, Meghan Addorisio, Jianhua Li, Michael J Postiglione, Sangeeta S Chavan, Yousef Al-Abed, Daniel J Antoine, Ulf Andersson, Kevin J Tracey
BACKGROUND: Extra-corpuscular hemoglobin is an endogenous factor enhancing inflammatory tissue damage, a process counteracted by the hemoglobin-binding plasma protein haptoglobin composed of alpha and beta subunits connected by disulfide bridges. Recent studies established that haptoglobin also binds and sequesters another pro-inflammatory mediator, HMGB1, via triggering CD163 receptor-mediated anti-inflammatory responses involving heme oxygenase-1 expression and IL-10 release. The molecular mechanism underlying haptoglobin-HMGB1 interaction remains poorly elucidated...
May 2, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28462386/association-of-variants-of-arginine-vasopressin-and-arginine%C3%A2-vasopressin-receptor-1a-with-severe-acetaminophen%C3%A2-liver-injury
#16
Matthew Randesi, Orna Levran, Joel Correa da Rosa, Julia Hankins, Jody Rule, Mary Jeanne Kreek, William M Lee
BACKGROUND & AIMS: Acetaminophen-related acute liver injury and liver failure (ALF) result from ingestion of supratherapeutic quantities of this analgesic, frequently in association with other forms of substance abuse including alcohol, opioids, and cocaine. Thus, overdosing represents a unique high-risk behavior associated with other forms of drug use disorder. METHODS: We examined a series of 21 single nucleotide polymorphisms (SNPs) in 9 genes related to impulsivity and/or stress responsivity that may modify response to stress...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28459937/cxcl16-deficiency-attenuates-acetaminophen-induced-hepatotoxicity-through-decreasing-hepatic-oxidative-stress-and-inflammation-in-mice
#17
Hong Wang, Yihui Shao, Saisai Zhang, Anqi Xie, Yanna Ye, Lihua Shi, Leigang Jin, Xuebo Pan, Zhuofeng Lin, Xiaokun Li, Shulin Yang
Chemokine C-X-C ligand 16 (CXCL16), a single-pass Type I membrane protein belonging to the CXC chemokine family, is related to the inflammatory response in liver injury. In present study, we investigated the pathophysiological role of CXCL16, a unique membrane-bound chemokine, in acetaminophen (APAP)-induced hepatotoxicity in mice. Mice were injected with APAP, and blood and tissue samples were harvested at different time points. The serum high-mobility group box 1 and CXCL16 levels were quantified by sandwich immunoassays...
April 28, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28447858/risk-prediction-of-hepatotoxicity-in-paracetamol-poisoning
#18
Anselm Wong, Andis Graudins
CONTEXT: Paracetamol (acetaminophen) poisoning is the most common cause of acute liver failure in the developed world. A paracetamol treatment nomogram has been used for over four decades to help determine whether patients will develop hepatotoxicity without acetylcysteine treatment, and thus indicates those needing treatment. Despite this, a small proportion of patients still develop hepatotoxicity. More accurate risk predictors would be useful to increase the early detection of patients with the potential to develop hepatotoxicity despite acetylcysteine treatment...
April 27, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28447517/hepatoprotective-potential-of-phyllanthus-muellarianus-leaf-extract-studies-on-hepatic-oxidative-stress-and-inflammatory-biomarkers
#19
Taofeek O Ajiboye, Fatimah M Ahmad, Airat O Daisi, Aminat A Yahaya, Oluwayemisi B Ibitoye, Hamdalat F Muritala, Taofik O Sunmonu
CONTEXT: Leaves of Phyllanthus muellarianus (Kuntze) Exell. (Euphorbiacea) are widely used in the management of liver disorders in Nigeria. However, no there is no scientific validation to support this use. OBJECTIVE: Hepatoprotective effect of Phyllanthus muellarianus aqueous leaf extract was investigated in acetaminophen-induced liver injury mice. MATERIALS AND METHODS: Hepatoprotective effect of Phyllanthus muellarianus aqueous leaf extract was evaluated in acetaminophen-induced hepatic damage in Swiss albino mice using biomarkers of hepatocellular indices, oxidative stress, proinflammatory factors and lipid peroxidation...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28444411/-acute-liver-failure
#20
A Koch, C Trautwein, F Tacke
Acute liver failure (ALF) is a rare, but life-threatening disease that is characterized by the acute onset of jaundice, coagulopathy, and hepatic encephalopathy (HE) in patients without pre-existing liver disease. Main causes in Germany are drug toxicity, acetaminophen overdose, and viral hepatitis (A, B, E). For the initial assessment of patients with ALF and the diagnostic algorithm, the early detection of HE, exclusion of liver cirrhosis, immediate diagnosis of the underlying etiology, and evaluation for the necessity of liver transplantation (LT) are critical...
May 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
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