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https://www.readbyqxmd.com/read/28919469/assignment-of-the-absolute-configuration-of-hepatoprotective-highly-oxygenated-triterpenoids-using-x-ray-ecd-nmr-j-based-configurational-analysis-and-hsqc-overlay-experiments
#1
Xiaojuan Wang, Jiabao Liu, Pankaj Pandey, Jiabao Chen, Frank R Fronczek, Stuart Parnham, Xinzhu Qi, Robert J Doerksen, Daneel Ferreira, Hua Sun, Shuai Li, Mark T Hamann
BACKGROUND: The plants of the genus Kadsura are widely distributed in China, South Korea, and Japan. Their roots and stems are traditionally used to treat blood diseases and pain. The main bioactive constituents of Kadsura longipedunculata comprise highly oxygenated triterpenoids. Schiartane-type nortriterpenoids showed anti-HIV, anti-HBV, and cytotoxic bioactivities. For such compounds, the absolute configuration influences the bioactivities, and hence its unambiguous determination is essential...
September 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28919358/perfused-human-hepatocyte-microtissues-identify-reactive-metabolite-forming-and-mitochondria-perturbing-hepatotoxins
#2
Cliff Rowe, Mohsen Shaeri, Emma Large, Terri Cornforth, Angela Robinson, Tomasz Kostrzewski, Rowena Sison-Young, Christopher Goldring, Kevin Park, David Hughes
Hepatotoxins cause liver damage via many mechanisms but the formation of reactive metabolites and/or damage to liver mitochondria are commonly implicated. We assess 3D human primary hepatocyte microtissues as a platform for hepatotoxicity studies with reactive metabolite-forming and mitochondria-perturbing compounds. We show that microtissues formed from cryopreserved human hepatocytes had bile canaliculi, transcribed mRNA from genes associated with xenobiotic metabolism and expressed functional cytochrome P450 enzymes...
September 15, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28918124/polyphenols-reported-to-shift-apap-induced-changes-in-mapk-signaling-and-toxicity-outcomes
#3
REVIEW
Ngoc Uy Nguyen, Brendan David Stamper
Due to its widespread availability, acetaminophen (APAP) is the leading cause for drug-induced liver injury in many countries including United States and United Kingdom. When used as recommended, APAP is relatively safe. However, in overdose cases, increased metabolism of APAP to N-acetyl-para-benzoquinoneimine (NAPQI), a reactive metabolite, leads to glutathione (GSH) depletion, oxidative stress, and cellular injury. Throughout this process, a variety of factors play important roles in propagating toxicity, including c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family...
September 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28913484/identification-of-significant-obstructive-sleep-apnoea-in-the-obese-patient-development-of-the-novel-dx-osa-score
#4
Daniela D Godoroja, Dan Adrian Cioc
BACKGROUND AND OBJECTIVES: There is a high prevalence of undiagnosed obstructive sleep apnoea (OSA) in obese surgical patients. We investigated the extent to which anthropometric measurements can be used to identify the presence of significant OSA (Apnoea/Hypopnoea Index (AHI) ≥ 20) in adult patients. MATERIALS AND METHODS: We prospectively studied 1357 adult patients scheduled for elective laparoscopic bariatric surgery. Prior to surgery, body mass index (BMI), gender, neck circumference, STOP-Bang score, SpO2, neck and trunk fat (by dual X-ray absorptiometry) were recorded...
October 2016: Rom J Anaesth Intensive Care
https://www.readbyqxmd.com/read/28911849/eight-new-phenylethanoid-glycoside-derivatives-possessing-potential-hepatoprotective-activities-from-the-fruits-of-forsythia-suspensa
#5
Si-Yuan Shao, Zi-Ming Feng, Ya-Nan Yang, Jian-Shuang Jiang, Pei-Cheng Zhang
In our study to investigate components with hepatoprotective activities, eight new phenylethanoid glycoside derivatives (1-8) were isolated from the 75% EtOH-H2O extract of the fruits of Forsythia suspensa along with six known compounds (9-14). These new structures were elucidated through HRESIMS and extensive NMR spectroscopic techniques. The absolute configurations of their sugars were determined by GC analysis. The pharmacological assay showed that compounds 2, 3, and 9-11 displayed remarkable hepatoprotective activities against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage at the concentration of 10μM (Bicyclol as positive contrast)...
September 11, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28899510/screening-of-hepatoprotective-compounds-from-licorice-against-carbon-tetrachloride-and-acetaminophen-induced-hepg2-cells-injury
#6
Yi Kuang, Yan Lin, Kai Li, Wei Song, Shuai Ji, Xue Qiao, Qingying Zhang, Min Ye
BACKGROUND: Licorice and its constituents, especially licorice flavonoids have been reported to possess significant hepatoprotective activities. However, previous studies mainly focus on the extract and major compounds, and few reports are available on other licorice compounds. PURPOSE: This work aims to evaluate the in vitro hepatoprotective activities of licorice compounds and screen active compounds, and to establish the structure-activity relationship. METHODS: A compound library consisting of 180 compounds from three medicinal licorice species, Glycyrrhiza uralensis, G...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28894628/tigernut-cyperus-esculentus-l-milk-as-a-potent-nutri-drink-for-the-prevention-of-acetaminophen-induced-hepatotoxicity-in-a-murine-model
#7
Nnenna Ola Onuoha, Nneoma Oleh Ogbusua, Augustine N Okorie, Chukwunonso E C C Ejike
AIM/BACKGROUND: Given the prevalence of toxicants in foods, beauty products, etc., and the increasing demand for "green" products, there is a need for the development of "nutri-drinks" with hepatoprotective properties. The usefulness of tigernut milk (TNM) in preventing acetaminophen (APAP)-induced liver injury was, therefore, investigated. MATERIALS AND METHODS: A total of 25 rats were randomized into five equal groups. Four groups were treated with 0, 500, 1000, and 2000 kg/mg body weight (bw) TNM, respectively, per os for 2 weeks before they were challenged with 2500 mg/kg bw APAP...
July 2017: Journal of Intercultural Ethnopharmacology
https://www.readbyqxmd.com/read/28878168/metabolomics-analysis-of-urine-samples-from-children-after-acetaminophen-overdose
#8
Laura K Schnackenberg, Jinchun Sun, Sudeepa Bhattacharyya, Pritmohinder Gill, Laura P James, Richard D Beger
Acetaminophen (APAP), a commonly used over-the-counter analgesic, accounts for approximately fifty percent of the cases of acute liver failure (ALF) in the United States due to overdose, with over half of those unintentional. Current clinical approaches for assessing APAP overdose rely on identifying the precise time of overdose and quantitating acetaminophen alanine aminotransferase (ALT) levels in peripheral blood. Novel specific and sensitive biomarkers may provide additional information regarding patient status post overdose...
September 6, 2017: Metabolites
https://www.readbyqxmd.com/read/28872689/metabolic-interactions-between-acetaminophen-paracetamol-and-two-flavonoids-luteolin-and-quercetin-through-in-vitro-inhibition-studies
#9
Lei Cao, Awewura Kwara, David J Greenblatt
OBJECTIVES: Excessive exposure to acetaminophen (APAP, paracetamol) can cause liver injury through formation of a reactive metabolite that depletes hepatic glutathione and causes hepatocellular oxidative stress and damage. Generation of this metabolite is mediated by Cytochrome-P450 (CYP) isoforms, mainly CYP2E1. A number of naturally occurring flavonoids can mitigate APAP-induced hepatotoxicity in experimental animal models. Our objective was to determine the mechanism of these protective effects and to evaluate possible human applicability...
September 5, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28867745/non-toxic-level-of-acetaminophen-potentiates-carbon-tetrachloride-induced-hepatotoxicity-in-mice
#10
Shiori Fukaya, Hiroki Yoshioka, Tadahiro Okano, Akito Nagatsu, Nobuhiko Miura, Tsunemasa Nonogaki, Satomi Onosaka
A wide range of medications are routinely used to maintain and improve human health. Hence, it is essential that we understand and predict adverse effects caused by the combined use of multiple medications. In the present study, we investigated whether the combination of carbon tetrachloride (CCl4) and acetaminophen (APAP) had a detrimental effect on the liver. Mice injected with APAP (100 mg/kg) showed no significant changes in hepatic injury markers (alanine aminotransferase and aspartate aminotransferase), histopathological findings, pro-inflammatory cytokine levels, or hepatic oxidative stress...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28867475/fibroblast-growth-factor-15-deficiency-increases-susceptibility-but-does-not-improve-repair-to-acetaminophen-induced-liver-injury-in-mice
#11
Mingxing Huang, Jessica Williams, Bo Kong, Yan Zhu, Guodong Li, Zhe Zhu, Grace L Guo
The leading cause of acute liver failure (ALF) is hepatotoxicity from acetaminophen (APAP) overdose. However, limited options are available to treat this ALF so stimulating liver regeneration maybe a potential treatment. Our previous study has shown that fibroblast growth factor 15 (FGF15) plays a crucial role in liver regeneration, but the roles of FGF15 in liver injury and repair following APAP-overdose are unknown. In this study, treatment of FGF15 knockout (KO) male mice with APAP at 200, 250, or 300mg/kg significantly increased the degree of liver injury compared to wild type (WT) mice...
August 12, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28867424/psychosocial-and-behavioral-factors-in-acetaminophen-related-acute-liver-failure-and-liver-injury
#12
Carla Pezzia, Corron Sanders, Suzanne Welch, Angela Bowling, William M Lee
OBJECTIVES: Acetaminophen overdoses result in nearly 500 deaths annually and a much larger number of hospitalizations. Suicidal overdoses are exceeded in number in the United States by unintentional overdoses. We evaluated clinical, demographic and psychosocial factors among unintentional and intentional overdose patients whose acetaminophen (APAP) toxicity had resulted in acute liver failure. We hypothesized that APAP overdose patients would be more likely to suffer from behavioral health issues and display higher impulsivity scores than the general population...
October 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28851249/bacterial-pneumonia-in-patients-with-liver-cirrhosis-with-or-without-hiv-co-infection-a-possible-definition-of-antibiotic-prophylaxis-associated-pneumonia-apap
#13
Gianluca Cuomo, Giuseppina Brancaccio, Gianfranca Stornaiuolo, Daniela Manno, Giuseppe L Gaeta, Cristina Mussini, Massimo Puoti, Giovanni B Gaeta
Introducion: Bacterial infections frequently complicate liver cirrhosis. The aim of this study was to identify risk factors and clinical impact of bacterial pneumonia in patients with cirrhosis. MATERIALS AND METHODS: Bacterial infection prevalence study: consecutive patients with cirrhosis were enroled over a six-month period in 13 Italian centres. Pneumonia and other infections were diagnosed by standard methods. Pneumonia study: cirrhotic patients with pneumonia were enroled for an additional six-month period and HIV-positive patients were included...
August 29, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28844483/serum-microrna-122-3p-microrna-194-5p-and-microrna-5099-are-potential-toxicological-biomarkers-for-the-hepatotoxicity-induced-by-airpotato-yam
#14
Rui Yang, Fan Yang, Zhenlin Huang, Yao Jin, Yuchen Sheng, Lili Ji
Airpotato yam (the rhizome of Dioscorea bulbifera L.) is traditionally used to treat thyroid disease and various cancers in China. However, it was found to cause hepatotoxicity during clinical practice. This study aims to identify candidate serum microRNAs (miRNAs) as diagnostic biomarkers for the liver injury induced by Airpotato yam. The results of serum alanine/aspartate aminotransferase (ALT/AST) showed the remarkable hepatotoxicity induced by ethyl acetate fraction of Airpotato yam (EF) (450mg/kg) and diosbulbin B (DB) (300mg/kg) in mice...
August 24, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28841174/purification-preliminary-characterization-and-hepatoprotective-effects-of-polysaccharides-from-dandelion-root
#15
Liangliang Cai, Dongwei Wan, Fanglian Yi, Libiao Luan
In this study, purification, preliminary characterization and hepatoprotective effects of water-soluble polysaccharides from dandelion root (DRP) were investigated. Two polysaccharides, DRP1 and DRP2, were isolated from DRP. The two polysaccharides were α-type polysaccharides and didn't contain protein. DRP1, with a molecular weight of 5695 Da, was composed of glucose, galactose and arabinose, whereas DRP2, with molecular weight of 8882 Da, was composed of rhamnose, galacturonic acid, glucose, galactose and arabinose...
August 25, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28839178/hypercoagulability-progresses-to-hypocoagulability-during-evolution-of-acetaminophen-induced-acute-liver-injury-in-pigs
#16
Karla Chui Luan Lee, Luisa Baker, Susan Mallett, Anne Riddell, Pratima Chowdary, Hatim Alibhai, Yu-Mei Chang, Simon Priestnall, Giacomo Stanzani, Nathan Davies, Rajeshwar Mookerjee, Rajiv Jalan, Banwari Agarwal
Increases in prothrombin time (PT) and international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF), yet a wide heterogeneity in clotting abnormalities exists. This study defines evolution of coagulopathy in 10 pigs with acetaminophen (APAP)-induced ALI compared to 3 Controls. APAP administration began at 0 h and continued to 'ALF', defined as INR >3. In APAP pigs, INR was 1.05 ± 0.02 at 0 h, 2.15 ± 0.43 at 16 h and > 3 at 18 ± 1 h. At 12 h thromboelastography (TEG) demonstrated increased clot formation rate, associated with portal vein platelet aggregates and reductions in protein C, protein S, antithrombin and A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats-13 (ADAMTS-13) to 60%, 24%, 47% and 32% normal respectively...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28836466/effect-of-acetaminophen-on-the-prevention-of-acute-kidney-injury-in-patients-with-sepsis
#17
Asad E Patanwala, Ohoud Aljuhani, Hussain Bakhsh, Brian L Erstad
BACKGROUND: Acute kidney injury (AKI) commonly occurs in patients with sepsis. Acetaminophen (APAP) has been shown to inhibit lipid peroxidation and, thus, may be renal protective in patients with sepsis. OBJECTIVE: The objective of this study was to determine the effect of APAP on AKI in patients with sepsis. METHODS: This was a retrospective cohort study conducted at 2 affiliated academic medical centers in the United States. Adult patients who were admitted to the intensive care unit with a diagnosis of severe sepsis were included...
August 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28832650/fructose-diet-alleviates-acetaminophen-induced-hepatotoxicity-in-mice
#18
Sungjoon Cho, Ashutosh Tripathi, George Chlipala, Stefan Green, Hyunwoo Lee, Eugene B Chang, Hyunyoung Jeong
Acetaminophen (APAP) is a commonly used analgesic and antipyretic that can cause hepatotoxicity due to production of toxic metabolites via cytochrome P450 (Cyp) 1a2 and Cyp2e1. Previous studies have shown conflicting effects of fructose (the major component in Western diet) on the susceptibility to APAP-induced hepatotoxicity. To evaluate the role of fructose-supplemented diet in modulating the extent of APAP-induced liver injury, male C57BL/6J mice were given 30% (w/v) fructose in water (or regular water) for 8 weeks, followed by oral administration of APAP...
2017: PloS One
https://www.readbyqxmd.com/read/28827191/silver-nanoparticles-protect-acetaminophen-induced-acute-hepatotoxicity-a-biochemical-and-histopathological-approach
#19
Mohd Salim Reshi, Chhavi Uthra, Deepa Yadav, Samta Sharma, Asha Singh, Anjali Sharma, Amita Jaswal, Neelu Sinha, Sadhana Shrivastava, Sangeeta Shukla
The present study was premeditated to demonstrate the hepatoprotective effect of silver nanoparticles (AgNPs). Rats were treated with three different doses of AgNPs (50, 100 and 150 μg/kg, p.o.) after Acetaminophen (APAP; 2 g/kg, p.o. once only) intoxication. Treatment with AgNPs recouped the levels of serum aspartate amino transaminase (AST), alanine amino transaminase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), bilirubin, triglyceride (TG) and cholesterol in dose dependent manner. Significant reduction in lipid peroxidation (LPO) and restoration of reduced glutathione (GSH) was found in liver in AgNPs treated animals...
August 19, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28827156/induction-of-mitochondrial-biogenesis-protects-against-acetaminophen-hepatotoxicity
#20
Kuo Du, Anup Ramachandran, Mitchell R McGill, Abdellah Mansouri, Tarik Asselah, Anwar Farhood, Benjamin L Woolbright, Wen-Xing Ding, Hartmut Jaeschke
Mitochondrial biogenesis (MB) is an adaptive response to maintain metabolic homeostasis after mitochondrial dysfunction. Induction of MB during APAP hepatotoxicity has not been studied. To investigate this, mice were treated with toxic doses of APAP and euthanized between 0 and 96 h. At early time points, APAP caused both mitochondrial dysfunction and reduction of mitochondrial mass, indicated by reduced activity of electron transport chain (ETC) complexes I and IV and depletion of mitochondrial DNA (mtDNA), respectively...
October 2017: Food and Chemical Toxicology
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