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acetaminophen and liver

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https://www.readbyqxmd.com/read/27913221/role-of-the-inflammasome-in-acetaminophen-induced-liver-injury-and-acute-liver-failure
#1
REVIEW
Benjamin L Woolbright, Hartmut Jaeschke
Drug-induced acute liver failure carries a high morbidity and mortality rate. Acetaminophen overdose is the number one cause of acute liver failure and remains a major problem in Western medicine. Administration of N-acetyl cysteine is an effective antidote when given before the initial rise in toxicity; however, many patients present to the hospital after this stage occurs. As such, treatments which can alleviate late-stage acetaminophen-induced acute liver failure are imperative. While the initial mechanisms of toxicity are well described, a debate has occurred recently in the literature over whether or not there exists a second phase of injury, mediated by inflammatory processes...
November 29, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27901623/autotransplantation-of-spleen-mitigates-drug-induced-liver-damage-in-splenectomized-mice
#2
Sabrine Teixeira Ferraz Grunewald, Alice Belleigoli Rezende, Bárbara Bruna Muniz Figueiredo, Ana Carolina de Paula Mendonça, Caroline de Souza Almeida, Erick Esteves de Oliveira, Flávia de Paoli, Henrique Couto Teixeira
PURPOSE: The spleen presents numerous functions, including the production of immunoglobulins and blood filtration, removing microorganisms and cellular debris. The spleen also has anatomical and functional relationship with the liver, but there are few studies on this topic. The aim of this study was to assess the effect of splenectomy and autologous spleen transplantation on both filtering functions of spleen and acetaminophen-induced hepatotoxicity. MATERIALS AND METHODS: Fifty-two BALB/c mice were randomized into four groups: splenectomized; splenectomy and splenic autotransplantation in the greater omentum; sham operated control; and non-operated control...
November 30, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/27900802/therapeutic-potential-of-carfilzomib-an-irreversible-proteasome-inhibitor-against-acetaminophen-induced-hepatotoxicity-in-mice
#3
Abdulrazaq Alanazi, Saleh G Algfeley, Khaled A Al-Hosaini, Hesham M Korashy, Faisal Imam, Mahmoud N Nagi
Overdose of acetaminophen (APAP) is often associated with hepatotoxicity. Carfilzomib (CFZ) shows multiple pharmacological activities including anti-inflammatory potential. Therefore, this study was undertaken to evaluate the possible therapeutic effects of CFZ against APAP-induced hepatotoxicity. Hepatotoxicity was induced by administration of APAP (350 mg/kg, intraperitoneal). Mice were given CFZ (0.125, 0.25, or 0.5 mg/kg, intraperitoneal) 1.5 h after APAP administration. Animals were sacrificed on 6 h and blood and liver tissue samples were collected for analysis...
November 30, 2016: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/27896824/patients-with-the-worst-outcomes-after-paracetamol-acetaminophen-induced-liver-failure-have-an-early-monocytopenia
#4
J K Moore, A C MacKinnon, T Y Man, J R Manning, S J Forbes, K J Simpson
BACKGROUND: Acute liver failure (ALF) is associated with significant morbidity and mortality. Studies have implicated the immune response, especially monocyte/macrophages as being important in dictating outcome. AIM: To investigate changes in the circulating monocytes and other immune cells serially in patients with ALF, relate these with cytokine concentrations, monocyte gene expression and patient outcome. METHODS: In a prospective case-control study in the Scottish Liver Transplant Unit, Royal Infirmary Edinburgh, 35 consecutive patients admitted with paracetamol-induced liver failure (POD-ALF), 10 patients with non-paracetamol causes of ALF and 16 controls were recruited...
November 28, 2016: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27891510/tropisetron-protects-against-acetaminophen-induced-liver-injury-via-suppressing-hepatic-oxidative-stress-and-modulating-the-activation-of-jnk-erk-mapk-pathways
#5
Fu-Chao Liu, Hung-Chen Lee, Chia-Chih Liao, Allen H Li, Huang-Ping Yu
Objectives. To investigate the protective effects of tropisetron on acetaminophen- (APAP-) induced liver injury in a mice model. Methods. C57BL/6 male mice were given tropisetron (0.3 to 10 mg/kg) 30 minutes before a hepatotoxic dose of acetaminophen (300 mg/kg) intraperitoneally. Twenty hours after APAP intoxication, sera alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activities, and liver histopathological changes were examined...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27889232/l-methionine-and-silymarin-a-comparison-of-prophylactic-protective-capabilities-in-acetaminophen-induced-injuries-of-the-liver-kidney-and-cerebral-cortex
#6
Olakunle J Onaolapo, Moses A Adekola, Taiwo O Azeez, Karimat Salami, Adejoke Y Onaolapo
We compared the relative protective abilities of silymarin and l-methionine pre-treatment in acetaminophen overdose injuries of the liver, kidney and cerebral cortex by assessing behaviours, antioxidant status, tissue histological changes and biochemical parameters of hepatic/renal function. Rats were divided into six groups of ten each; animals in five of these groups were pre-treated with oral distilled water, silymarin (25mg/kg) or l-methionine (2.5, 5 and 10mg/kg body weight) for 14days; and then administered intraperitoneal (i...
November 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27880040/acetaminophen-overdoses-active-component-u-s-armed-forces-2006-2015
#7
Leslie L Clark, Stephen B Taubman
Acetaminophen, a drug commonly used to relieve pain and fever, is generally safe and effective when used as directed. However, acetaminophen overdose can cause serious adverse events, including liver damage and death. From 2006 through 2015, a total of 2,588 cases of acetaminophen overdose were identified in active component military members. Rates of acetaminophen overdose declined during this 10-year surveillance period, from 2.2 cases per 10,000 person-years (p-yrs) in 2006 to 1.2 cases per 10,000 p-yrs in 2015...
November 2016: MSMR
https://www.readbyqxmd.com/read/27873239/effects-of-acetaminophen-on-mitochondrial-complex-i-activity-in-the-rat-liver-and-kidney-a-pet-study-with-18-f-bcpp-bf
#8
Hiroyuki Ohba, Masakatsu Kanazawa, Takeharu Kakiuchi, Hideo Tsukada
BACKGROUND: In the present study, 2-tert-butyl-4-chloro-5-[6-(4-(18)F-fluorobutoxy)-pyridin-3-ylmethoxy]-2H-pyridazin-3-one ((18)F-BCPP-BF), a PET probe for mitochondrial complex I (MC-I), was used to validate whether MC-I is a useful biomarker for detecting acetaminophen-induced dysfunctions in the liver and kidney. The kinetic and distribution of (18)F-BCPP-BF were assessed in rats using high-resolution animal PET in vivo. The binding specificity of (18)F-BCPP-BF to MC-I in the liver and kidney was confirmed by the pre-administration of rotenone, a specific MC-I inhibitor...
December 2016: EJNMMI Research
https://www.readbyqxmd.com/read/27872193/critical-contribution-of-nuclear-factor-erythroid-2-related-factor-2-nrf2-to-electrophile-induced-interleukin-11-production
#9
Takashi Nishina, Yutaka Deguchi, Ryosuke Miura, Soh Yamazaki, Yasuhiro Shinkai, Yuko Kojima, Ko Okumura, Yoshito Kumagai, Hiroyasu Nakano
Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that plays a crucial role in protection of cells from electrophile-induced toxicity through upregulating phase II detoxifying enzymes and phase III transporters. We previously reported that oxidative stress induces upregulation of interleukin-11 (IL-11), a member of the IL-6 family that ameliorates acetaminophen-induced liver toxicity. However, a role for IL-11 in protection of cells from electrophile-induced toxicity remains unclear...
November 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27871602/hepatotoxicity-due-to-red-bush-tea-consumption-a-case-report
#10
Shamantha Reddy, Pragnyadipta Mishra, Sana Qureshi, Singh Nair, Tracey Straker
Many conventional drugs used today, including isoniazid, dapsone, and acetaminophen, are well recognized culprits of hepatotoxicity. With increasing use of complementary and alternative medical therapies, several herbal medicines, such as Ma-Huang, kava, and chaparral leaf, have been implicated as hepatotoxins. Hepatotoxicity may be the most frequent adverse reaction to these herbal remedies when taken in excessive quantities. A myriad of liver dysfunctions may occur including transient liver enzyme abnormalities due to acute and chronic hepatitis...
December 2016: Journal of Clinical Anesthesia
https://www.readbyqxmd.com/read/27866976/protective-effect-of-rosiglitazone-against-acetaminophen-induced-acute-liver-injury-is-associated-with-down-regulation-of-hepatic-nadph-oxidases
#11
Jun-Xian Wang, Cheng Zhang, Lin Fu, Da-Gang Zhang, Bi-Wei Wang, Zhi-Hui Zhang, Yuan-Hua Chen, Yan Lu, Xi Chen, De-Xiang Xu
The peroxisome proliferator-activated receptor gamma (PPAR-γ) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism. The aim of the present study was to investigate the effects of rosiglitazone (RSG), a synthetic PPAR-γ agonist, on acetaminophen (APAP)-induced acute liver injury. Male CD-1 mice were injected with APAP (300mg/kg). Some mice were pretreated with RSG (20mg/kg) 48, 24 and 1h before APAP injection. As expected, RSG pretreatment alleviated APAP-induced acute liver injury...
November 17, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27862262/different-effects-of-selective-%C3%AE-1-adrenoceptor-antagonists-nebivolol-or-atenolol-in-acetaminophen-induced-heptatotoxicity-of-rats
#12
Remon R Rofaeil, Maha Yehia Kamel, Walaa Yehia Abdelzaher
Acetaminophen (APAP) overdose is a common cause of acute liver failure and beta blockers are commonly used drugs in clinical practice. This study aims to evaluate the effect of two different beta blockers agents as nebivolol and atenolol against APAP-induced hepatotoxicity. Male wistar rats were treated with APAP (2 g/kg/day, p.o.) to induce hepatotoxicity. Our results showed that nebivolol and atenolol reduced heart rate and blood pressure. Nebivolol (5 mg/kg /day, p.o.) for 14 days has a hepatoprotective effect shown by significant decrease in hepatic injury parameters (serum AST and ALT) with significant suppression of hepatic malondialdehyde (MDA) and nitric oxide (NO) which were elevated with APAP administration...
November 14, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27862231/early-stage-functions-of-mitochondrial-autophagy-and-oxidative-stress-in-acetaminophen-induced-liver-injury
#13
Yan Gao, Shifeng Chu, Zhao Zhang, Wei Zuo, Congyuan Xia, Qidi Ai, Piao Luo, Peng Cao, Naihong Chen
Mitochondria go through frequent cycles of fusion and fission, a process required for mitochondrial quality control by eliminating ROS-damaged mitochondria through mitochondrial autophagy. Acetaminophen (APAP) overdose can cause liver injury in animals and human beings by inducing mitochondrial damage, which need to be further evaluated. The aim of the current study is to assess the changes between oxidative damage and mitophagy in vivo and in vitro, which mimics APAP-induced liver injury (AILI) in humans. Liver damage was monitored by measuring the levels of biochemical indexes...
November 9, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27861792/drug-induced-liver-injury-advances-in-mechanistic-understanding-that-will-inform-risk-management
#14
Merrie Mosedale, Paul B Watkins
Drug-induced liver injury (DILI) is a major public health problem. Intrinsic (dose-dependent) DILI associated with acetaminophen overdose is the number one cause of acute liver failure in the US. However the most problematic type of DILI impacting drug development is idiosyncratic, occurring only very rarely among treated patients and often only after several weeks or months of treatment with the offending drug. Recent advances in our understanding of the pathogenesis of DILI suggest that three mechanisms may underlie the hepatocyte effects in response to both intrinsic and idiosyncratic DILI drugs: mitochondrial dysfunction, oxidative stress, and alterations in bile acid homeostasis...
November 9, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27859489/elevated-fabp1-serum-levels-are-associated-with-poorer-survival-in-acetaminophen-induced-acute-liver-failure
#15
Constantine J Karvellas, Jaime L Speiser, Mélanie Tremblay, William M Lee, Christopher F Rose
BACKGROUND/AIM: Acetaminophen (APAP)-induced Acute Liver Failure (ALF) is associated with significant mortality. Traditional prognostic scores lack sensitivity. HYPOTHESIS: Serum Liver-type Fatty Acid Binding Protein (FABP1) early (day 1) or late (day 3-5) levels are associated with 21-day mortality in the absence of liver transplant. METHODS: Serum samples from 198 APAP-ALF patients (nested case control study with 99 survivors, 99 non-survivors) were analyzed by ELISA methods and assessed with clinical data from the US Acute Liver Failure Study Group (ALFSG) Registry (1998-2014)...
November 18, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27855209/baicalin-attenuates-il-17-mediated-acetaminophen-induced-liver-injury-in-a-mouse-model
#16
Chia-Chih Liao, Yuan-Ji Day, Hung-Chen Lee, Jiin-Tarng Liou, An-Hsun Chou, Fu-Chao Liu
BACKGROUND: IL-17 has been shown to be involved in liver inflammatory disorders in both mice and humans. Baicalin (BA), a major compound extracted from traditional herb medicine (Scutellariae radix), has potent hepatoprotective properties. Previous study showed that BA inhibits IL-17-mediated lymphocyte adhesion and downregulates joint inflammation. The aim of this study is to investigate the role of IL-17 in the hepatoprotective effects of BA in an acetaminophen (APAP)-induced liver injury mouse model...
2016: PloS One
https://www.readbyqxmd.com/read/27850231/591-an-established-dosing-of-n-acetylcysteine-in-non-acetaminophen-induced-acute-liver-failure
#17
Justin Kinney, Nam Cho
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27850213/573-brain-fabp-serum-levels-and-clinical-outcomes-in-acetaminophen-induced-acute-liver-failure
#18
Constantine Karvellas, Jaime Speiser, Melanie Tremblay, William Lee, Christopher Rose
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27847654/the-case-for-improved-interprofessional-care-fatal-analgesic-overdose-secondary-to-acute-dental-pain-during-pregnancy
#19
Sarah K Y Lee, Rocio B Quinonez, Alice Chuang, Stephanie M Munz, Darya Dabiri
Prenatal oral health extends beyond the oral cavity, impacting the general well-being of the pregnant patient and her fetus. This case report follows a 19-year-old pregnant female presenting with acute liver failure secondary to acetaminophen overdose for management of dental pain following extensive dental procedures. Through the course of her illness, the patient suffered adverse outcomes including fetal demise, acute kidney injury, spontaneous bacterial peritonitis, and septic shock before eventual death from multiple organ failure...
2016: Case Reports in Dentistry
https://www.readbyqxmd.com/read/27846064/serum-acetaminophen-protein-adduct-concentrations-in-pediatric-emergency-department-patients
#20
Kennon Heard, Victoria Anderson, Richard C Dart, Deidre Kile, Eric Lavonas, Jody L Green
: Acetaminophen toxicity is a common cause of pediatric liver failure. The diagnosis may be limited by the short window of detection of acetaminophen in serum. Recently acetaminophen protein adducts (APAP-CYS) have been used as a biomarker with a longer duration of detection. The objective of this study was to describe the serum concentrations of APAP-CYS in pediatric patients with and without reported therapeutic acetaminophen exposure. METHODS: A cross sectional study of children age 1 to <12 years presenting to a pediatric emergency department...
November 14, 2016: Journal of Pediatric Gastroenterology and Nutrition
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