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acetaminophen and liver

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https://www.readbyqxmd.com/read/28934748/severe-drug-induced-liver-injury-as-an-adverse-drug-event-of-antibiotics-a-case-report-and-review-of-the-literature
#1
Martin Munz, Hans Grummich, Josef Birkmann, Martin Wilhelm, Ulrike Holzgrabe, Fritz Sörgel
Drug-induced liver injury is one of the main reasons for acute liver failure. We report the case of a young patient who experienced a drug-induced liver injury resulting in life-threatening acute liver failure after treatment with different antibiotics (amoxicillin, ciprofloxacin, cefazolin, clindamycin) and acetaminophen, or a combination of these drugs. Moreover, we provide an overview of the hepatotoxic potential of these drugs.
September 22, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28933094/-protective-effects-of-luteolin-against-acetaminophen-induced-damage-in-l02-liver-cells
#2
Lan-Zhi He, Ya-Kun Meng, Yan-Zhong Han, Zhen-Fang Zhang, Ping Yin, Xiu-Xiu Sang, Xiao-He Xiao, Zhao-Fang Bai
This paper was aimed to investigate the protective effects of luteolin (Lut) against acetaminophen(APAP)-induced damage in L02 liver cells. CCK-8 was used to detect the cell activation of L02 cells treated by different Lut. The concentration and time of APAP induced L02 cell damage was screened. The effect of Lut on APAP induced apoptosis of L02 cells was detected by cell morphological observation, CCK-8 assay and flow cytometry. The contents of MDA, GSH and SOD activity in cell supernatant were detected by colorimetric assay...
November 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28924552/schisandra-sphenanthera-extract-wuzhi-tablet-protects-against-chronic-binge-and-acute-alcohol-induced-liver-injury-by-regulating-the-nrf2-are-pathway-in-mice
#3
Xuezhen Zeng, Xi Li, Chenshu Xu, Fulin Jiang, Yufei Mo, Xiaomei Fan, Yaoting Li, Yiming Jiang, Dongshun Li, Min Huang, Huichang Bi
Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract from Schisandra sphenanthera that is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding...
September 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28919358/perfused-human-hepatocyte-microtissues-identify-reactive-metabolite-forming-and-mitochondria-perturbing-hepatotoxins
#4
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
#5
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/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/28893642/enzyme-inducing-effects-of-berberine-on-cytochrome-p450-1a2-in-vitro-and-in-vivo
#8
Bo Jiang, Liyuan Meng, Feng Zhang, Xiaoling Jin, Guiliang Zhang
AIMS: Berberine (BER) is an important anti-bacterial drug from Chinese herbal medicine and a novel drug candidate for preclinical development in recent years. Here we provide evidence that the effects of berberine on cytochrome P450 (CYP) 1A2 in vitro and in vivo. MAIN METHODS: Real-time polymerase chain reaction and western blotting analysis were employed to evaluate the CYP1A2 mRNA levels and protein expression. The enzyme activity was assessed by the metabolic rate of phenacetin to acetaminophen by LC-MS/MS method...
September 8, 2017: Life Sciences
https://www.readbyqxmd.com/read/28891378/in-vitro-inhibition-of-human-ugt-isoforms-by-ritonavir-and-cobicistat
#9
Sara Algeelani, Novera Alam, Md Amin Hossain, Gerd Mikus, David J Greenblatt
1. Ritonavir and cobicistat are pharmacokinetic boosting agents used to increase systemic exposure to other antiretroviral therapies. The manufacturer's data suggests that cobicistat is a more selective CYP3A4 inhibitor than ritonavir. However, the inhibitory effect of ritonavir and cobicistat on human UDP glucuronosyltransferase (UGT) enzymes in Phase II metabolism is not established. This study evaluated the inhibition of human UGT isoforms by ritonavir versus cobicistat. 2. Acetaminophen and ibuprofen were used as substrates to evaluate the metabolic activity of the principal human UGTs...
September 11, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28878168/metabolomics-analysis-of-urine-samples-from-children-after-acetaminophen-overdose
#10
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/28874859/editorial-severe-acute-liver-injury-cause-connects-to-outcome
#11
EDITORIAL
Curtis K Argo, Stephen H Caldwell
Severe acute liver injury (ALI) is a common condition with little objective study of its natural history and outcomes. In this paper by Koch et al. and the Acute Liver Failure (ALF) Study Group, the authors utilize a consensus definition of ALI requiring newly elevated bilirubin, alanine aminotransferase (ALT), and international normalized ration (INR) without evidence of hepatic encephalopathy (HE), with HE as the key differentiator of ALI from ALF. They show significantly higher rates of progression to ALF, liver transplantation, or death in non-acetaminophen etiologies of ALI...
September 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28874772/antibody-dependent-fragmentation-is-a-newly-identified-mechanism-of-cell-killing-in-vivo
#12
Pei Xiong Liew, Jung Hwan Kim, Woo-Yong Lee, Paul Kubes
The prevailing view is that therapeutic antibodies deplete cells through opsonization and subsequent phagocytosis, complement-dependent lysis or antibody-dependent cellular-cytotoxicity. We used high resolution in vivo imaging to identify a new antibody-dependent cell death pathway where Kupffer cells ripped large fragments off crawling antibody-coated iNKT cells. This antibody-dependent fragmentation process resulted in lethality and depletion of crawling iNKT cells in the liver sinusoids and lung capillaries...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28872689/metabolic-interactions-between-acetaminophen-paracetamol-and-two-flavonoids-luteolin-and-quercetin-through-in-vitro-inhibition-studies
#13
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/28871174/erythropoietin-enhances-kupffer-cell-number-and-activity-in-the-challenged-liver
#14
Dafna Gilboa, Yasmin Haim-Ohana, Naamit Deshet-Unger, Nathalie Ben-Califa, Sahar Hiram-Bab, Debby Reuveni, Ehud Zigmond, Max Gassmann, Yankel Gabet, Chen Varol, Drorit Neumann
Erythropoietin (EPO) is the main hormone driving mammalian erythropoiesis, with activity mediated via the surface receptor, EPO-R, on erythroid progenitor cells. Recombinant human EPO is currently used clinically for the treatment of anemia in patients with end-stage renal disease, and in certain cancer patients suffering from anemia induced either by the tumor itself or by chemotherapy. EPO-R expression is also detected in non-erythroid cells, including macrophages present in the peritoneum, spleen, and bone marrow (BM)...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28867745/non-toxic-level-of-acetaminophen-potentiates-carbon-tetrachloride-induced-hepatotoxicity-in-mice
#15
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/28867738/characterization-of-%C3%AE-estradiol-3-glucuronidation-in-rat-brain
#16
Yuki Asai, Yukiko Sakakibara, Haruka Onouchi, Masayuki Nadai, Miki Katoh
β-Estradiol is conjugated by uridine 5'-diphosphate-glucuronosyltransferase (UGT) 1A to 3-glucuronide in the human liver. UGT1A has been found in the brain; therefore, UGT1A may be involved in β-estradiol 3-glucuronidation in the brain. In the present study, we aimed to characterize the β-estradiol 3-glucuronidation reaction in the rat brain. β-Estradiol 3-glucuronidation was detected in eight rat brain regions (cerebellum, frontal cortex, parietal cortex, piriform cortex, hippocampus, medulla oblongata, striatum, and thalamus)...
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
#17
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
#18
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/28844483/serum-microrna-122-3p-microrna-194-5p-and-microrna-5099-are-potential-toxicological-biomarkers-for-the-hepatotoxicity-induced-by-airpotato-yam
#19
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
#20
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
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