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https://www.readbyqxmd.com/read/28236354/synthetic-biomarker-design-using-analyte-responsive-acetaminophen
#1
Tatsuya Nishihara, Joe Inoue, Sho Tabata, Shinnosuke Murakami, Takamasa Ishikawa, Natsumi Saito, Shinji Fukuda, Masaru Tomita, Tomoyoshi Soga
The use of synthetic biomarkers is an emerging technique to improve disease diagnosis. Here, we report a novel design strategy using analyte-responsive acetaminophen (APAP) to expand the catalog of analytes available for synthetic biomarker development. As a proof-of-concept, we designed hydrogen peroxide (H₂O₂)-responsive APAP (HR-APAP) and succeeded in H₂O₂ detection with cellular and animal experiments. In fact, using blood samples following HR-APAP injection, we demonstrated that the plasma concentration ratio of [APAP + APAP conjugates]/[HR-APAP] could accurately represent differences of in vivo H₂O₂ levels...
February 25, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28225807/increased-liver-specific-proteins-in-circulating-extracellular-vesicles-as-potential-biomarkers-for-drug-and-alcohol-induced-liver-injury
#2
Young-Eun Cho, Eun-Ju Im, Pyong-Gon Moon, Esteban Mezey, Byoung-Joon Song, Moon-Chang Baek
Drug- and alcohol-induced liver injury are a leading cause of liver failure and transplantation. Emerging evidence suggests that extracellular vesicles (EVs) are a source of biomarkers because they contain unique proteins reflecting the identity and tissue-specific origin of the EV proteins. This study aimed to determine whether potentially hepatotoxic agents, such as acetaminophen (APAP) and binge alcohol, can increase the amounts of circulating EVs and evaluate liver-specific EV proteins as potential biomarkers for liver injury...
2017: PloS One
https://www.readbyqxmd.com/read/28216953/therapeutic-potential-of-alpha-ketoglutarate-against-acetaminophen-induced-hepatotoxicity-in-rats
#3
Lalita Mehra, Yasha Hasija, Gaurav Mittal
OBJECTIVE: Alpha-ketoglutarate (α-KG) is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary α-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of α-KG in acetaminophen (APAP) induced toxicity in rats...
October 2016: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/28210203/wnt-%C3%AE-catenin-signaling-drives-thioacetamide-mediated-heteroprotection-against-acetaminophen-induced-lethal-liver-injury
#4
Vivekkumar P Dadhania, Bharat Bhushan, Udayan Apte, Harihara M Mehendale
Preplacement of compensatory tissue repair (CTR) by exposure to a nonlethal dose of a toxicant protects animals against a lethal dose of another toxicant. Although CTR is known to heteroprotect, the underlying molecular mechanisms are not completely known. Here, we investigated the mechanisms of heteroprotection using thioacetamide (TA): acetaminophen (APAP) heteroprotection model. Male Swiss Webster mice received a low dose of TA or distilled water (DW) vehicle 24 hours prior to a lethal dose of APAP. Liver injury, tissue repair, and promitogenic signaling were studied over a time course of 24 hours after APAP overdose to the TA- and DW-primed mice (TA + APAP and DW + APAP, respectively)...
January 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28209544/sestrin2-protects-against-acetaminophen-induced-liver-injury
#5
Seung Jung Kim, Kyu Min Kim, Ji Hye Yang, Sam Seok Cho, Sang Kyu Lee, Sae Kwang Ku, Il Je Cho, Sung Hwan Ki
Acetaminophen (APAP) overdose accounts for half of the cases of acute liver failure worldwide. We previously reported that that Sestrin2 (Sesn2) protects against d-galactosamine/lipopolysaccharide-induced acute fulminant liver failure. In this study, we demonstrated that Sesn2 protects APAP-induced liver injury in mice, using a recombinant adenovirus encoding Sesn2 (Ad-Sesn2). First, we found that treatment of mice with toxic levels of APAP significantly reduced Sesn2 expression. Tail-vein injection with Ad-Sesn2 inhibited APAP-induced serum alanine aminotransferase and aspartate aminotransferase levels and markedly reduced hepatocyte degeneration and inflammatory cell infiltration...
February 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28208250/simultaneous-voltammetric-determination-of-acetaminophen-and-isoniazid-hepatotoxicity-related-drugs-utilizing-bismuth-oxide-nanorod-modified-screen-printed-electrochemical-sensing-platforms
#6
Bahaa G Mahmoud, Mohamed Khairy, Farouk A Rashwan, Craig E Banks
To overcome the recent outbreaks of hepatotoxicity-related drugs, a new analytical tool for the continuously determination of these drugs in human fluids is required. Electrochemical-based analytical methods offer an effective, rapid, and simple tool for on-site determination of various organic and inorganic species. However, the design of a sensitive, selective, stable, and reproducible sensor is still a major challenge. In the present manuscript, a facile, one-pot hydrothermal synthesis of bismuth oxide (Bi2O2...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28205631/immature-mice-are-more-susceptible-than-adult-mice-to-acetaminophen-induced-acute-liver-injury
#7
Yan Lu, Cheng Zhang, Yuan-Hua Chen, Hua Wang, Zhi-Hui Zhang, Xi Chen, De-Xiang Xu
Acetaminophen (APAP) overdose induces acute liver injury. The aim of the present study was to analyze the difference of susceptibility between immature and adult mice to APAP-induced acute liver injury. Weanling immature and adult mice were injected with APAP (300 mg/kg). As expected, immature mice were more susceptible than adult mice to APAP-induced acute liver injury. APAP-evoked hepatic c-Jun N-terminal kinase phosphorylation was stronger in immature mice than in adult mice. Hepatic receptor-interacting protein (RIP)1 was obviously activated at APAP-exposed immature and adult mice...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197107/augmentation-of-psychotherapy-through-alternative-preconscious-priming-a-case-series-exploring-effects-on-residual-symptoms
#8
Melha Zidani, Jean-Sébastien Audet, François Borgeat, Frederick Aardema, Kieron Philip O'Connor, Yasser Khazaal
The current paper describes a case series using a new strategy for facilitating change based on Augmentation of Psychotherapy through Alternative Preconscious Priming (APAP) (1) in the treatment of eight treatment-resistant patients suffering from social phobia or generalized anxiety disorder. The patients had previously only shown a partial response to cognitive behavioral therapy (CBT) despite good treatment adherence. The patients completed APAP using a computerized program, which consisted of three steps during which alternative, more functional thoughts and beliefs relevant to the idiosyncratic difficulties experienced by the patients were formulated...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28196650/protective-role-of-p53-in-acetaminophen-hepatotoxicity
#9
Yazhen Huo, Shutao Yin, Mingzhu Yan, Sanda Win, Tin Aung Than, Mariam Aghajan, Hongbo Hu, Neil Kaplowitz
p53 is a tumor suppressor with a pro-death role in many conditions. However, in some contexts, evidence supports a pro-survival function. p53 has been shown to be activated in acetaminophen (APAP) toxicity but the impact of this on toxicity is uncertain. In the present study, we have found that p53 plays a protective role in APAP-induced liver injury. We inhibited p53 using three different approaches in mice, pifithrin-α (PFTα), knockdown of p53 expression with antisense oligonucleotide, and p53 knockout...
February 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28194962/high-speed-quantitative-uplc-ms-analysis-of-multiple-amines-in-human-plasma-and-serum-via-precolumn-derivatization-with-6-aminoquinolyl-n-hydroxysuccinimidyl-carbamate-application-to-acetaminophen-induced-liver-failure
#10
Nicola Gray, Rabiya Zia, Adam King, Vishal C Patel, Julia Wendon, Mark J W McPhail, Muireann Coen, Robert S Plumb, Ian D Wilson, Jeremy K Nicholson
A targeted reversed-phase gradient UPLC-MS/MS assay has been developed for the quantification /monitoring of 66 amino acids and amino-containing compounds in human plasma and serum using precolumn derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQTag Ultra). Derivatization of the target amines required minimal sample preparation and resulted in analytes with excellent chromatographic and mass spectrometric detection properties. The resulting method, which requires only 10 μL of sample, provides the reproducible and robust separation of 66 analytes in 7...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28189026/mass-spectrometry-based-in%C3%A2-vitro-assay-investigations-on-the-transformation-of-pharmaceutical-compounds-by-oxidative-enzymes
#11
Lara F Stadlmair, Thomas Letzel, Jörg E Drewes, Johanna Graßmann
The ubiquitous presence of trace organic chemicals in wastewater and surface water leads to a growing demand for novel removal technologies. The use of isolated enzymes has been shown to possess the capability for a targeted application but requires a clearer mechanistic understanding. In this study, the potential of peroxidase from horseradish (HRP) and laccase from Pleurotus ostreatus (LccPO) to transform selected trace organic chemicals was studied using mass spectrometry (MS)-based in vitro enzyme assays...
May 2017: Chemosphere
https://www.readbyqxmd.com/read/28188341/evaluation-of-transcriptomic-signature-as-a-valuable-tool-to-study-drug-induced-cholestasis-in-primary-human-hepatocytes
#12
Céline Parmentier, Philippe Couttet, Armin Wolf, Thomas Zaccharias, Bruno Heyd, Philippe Bachellier, Marianne Uteng, Lysiane Richert
Primary human hepatocyte (PHH) sandwich cultures from five different donors were daily exposed to cyclosporine A (CsA), ibuprofen (IBU), chlorpromazine (CPZ), amiodarone (AMI) and paracetamol (APAP) at their respective Cmax (total) for short-term (1-3 days) and long-term treatment (14 days). Whole genome mRNA profiles (34,693 genes in total) were conducted using an Illumina microarray platform. The impact of compound treatments on gene signatures involved in liver differentiation, cholestasis and in bile acid homeostasis was evaluated...
February 10, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28169862/quantification-of-acetaminophen-and-its-metabolites-in-plasma-using-uplc-ms-doors-open-to-therapeutic-drug-monitoring-in-special-patient-populations
#13
Robert B Flint, Paola Mian, Bart van der Nagel, Nuria Slijkhuis, Birgit C P Koch
BACKGROUND: Acetaminophen (APAP, paracetamol) is the most commonly used drug for pain and fever in both the United States and Europe and considered safe when used at registered dosages. Nevertheless, differences between specific populations lead to remarkable changes in exposure to potentially toxic metabolites. Furthermore, extended knowledge is required on metabolite formation following intoxication, to optimize antidote treatment. Therefore, the authors aimed to develop and validate a quick and easy analytical method for simultaneous quantification of APAP, APAP-glucuronide, APAP-sulfate, APAP-cysteine, APAP-glutathione, APAP-mercapturate, and protein-derived APAP-cysteine in human plasma by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-MS/MS)...
February 6, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28165728/hepatoprotective-effect-of-%C3%AF-glutathione-in-a-murine-model-of-acetaminophen-induced-liver-toxicity
#14
Swati S More, Jaime Nugent, Ashish P Vartak, Steffan M Nye, Robert Vince
Ψ-Glutathione (ψ-GSH) is an orally bioavailable and metabolism-resistant glutathione analogue that has been shown previously to substitute glutathione in most of its biochemical roles. Described here in its entirety is the preclinical evaluation of ψ-GSH as a rescue agent for acetaminophen (APAP) overdose: an event where time is of essence. By employing a murine model, four scenarios commonly encountered in emergency medicine are reconstructed. ψ-GSH is juxtaposed against N-acetylcysteine (NAC), the sole clinically available drug, in each of the scenarios...
February 16, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28165393/reduced-sharpin-and-lubac-formation-may-contribute-to-ccl%C3%A2-or-acetaminophen-induced-liver-cirrhosis-in-mice
#15
Takeshi Yamamotoya, Yusuke Nakatsu, Yasuka Matsunaga, Toshiaki Fukushima, Hiroki Yamazaki, Sunao Kaneko, Midori Fujishiro, Takako Kikuchi, Akifumi Kushiyama, Fuminori Tokunaga, Tomoichiro Asano, Hideyuki Sakoda
Linear ubiquitin chain assembly complex (LUBAC), composed of SHARPIN (SHANK-associated RH domain-interacting protein), HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1), and HOIP (HOIL-1L interacting protein), forms linear ubiquitin on nuclear factor-κB (NF-κB) essential modulator (NEMO) and induces NF-κB pathway activation. SHARPIN expression and LUBAC formation were significantly reduced in the livers of mice 24 h after the injection of either carbon tetrachloride (CCl₄) or acetaminophen (APAP), both of which produced the fulminant hepatitis phenotype...
February 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28163558/effect-of-intravenous-acetaminophen-on-post-anesthesia-care-unit-length-of-stay-opioid-consumption-pain-and-analgesic-drug-costs-after-ambulatory-surgery
#16
Moteb A Khobrani, James M Camamo, Asad E Patanwala
OBJECTIVES: The primary objective was to assess whether the use of intravenous acetaminophen (APAP) in the ambulatory surgery setting is associated with a decreased length of stay in the post-anesthesia care unit (PACU). The secondary outcomes evaluated were pain scores, opioid consumption, and total cost of analgesics used in the PACU. METHODS: This was a retrospective cohort study conducted in adult patients (18 years of age or older) who received an eye, ear, nose, or throat (EENT) procedure at an outpatient surgery center between January 2014 and January 2015...
February 2017: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/28153389/gold-nanoparticles-ameliorate-acetaminophen-induced-hepato-renal-injury-in-rats
#17
Mohd Salim Reshi, Sadhana Shrivastava, Amita Jaswal, Neelu Sinha, Chhavi Uthra, Sangeeta Shukla
Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2g/kg p.o. once only. After 24h of APAP intoxication, animals were treated with three different doses of AuNPs (50μg/kg, 100μg/kg, 150μg/kg) orally or silymarin at a dose of 50mg/kg p.o., once only. Animals of all the groups were sacrificed after 24h of last treatment...
January 30, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28152447/astaxanthin-pretreatment-attenuates-acetaminophen-induced-liver-injury-in-mice
#18
Jingyao Zhang, Simin Zhang, Jianbin Bi, Jingxian Gu, Yan Deng, Chang Liu
BACKGROUND: Acetaminophen (APAP) is a conventional drug widely used in the clinic because of its antipyretic-analgesic effects. However, accidental or intentional APAP overdoses induce liver injury and even acute liver failure (ALF). Astaxanthin (ASX) is the strongest antioxidant in nature that shows preventive and therapeutic properties, such as ocular protection, anti-tumor, anti-diabetes, anti-inflammatory, and immunomodulatory effects. The aim of present study was to determine whether ASX pretreatment provides protection against APAP-induced liver failure...
January 31, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28130915/multiscale-modeling-reveals-inhibitory-and-stimulatory-effects-of-caffeine-on-acetaminophen-induced-toxicity-in-humans
#19
C Thiel, H Cordes, V Baier, L M Blank, L Kuepfer
Acetaminophen (APAP) is a widely used analgesic drug that is frequently co-administered with caffeine (CAF) in the treatment of pain. It is well known that APAP may cause severe liver injury after an acute overdose. However, the understanding of whether and to what extent CAF inhibits or stimulates APAP-induced hepatotoxicity in humans is still lacking. Here, a multiscale analysis is presented that quantitatively models the pharmacodynamic (PD) response of APAP during co-medication with CAF. Therefore, drug-drug interaction (DDI) processes were integrated into physiologically based pharmacokinetic (PBPK) models at the organism level, whereas drug-specific PD response data were contextualized at the cellular level...
January 28, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28123000/dual-role-of-epidermal-growth-factor-receptor-in-liver-injury-and-regeneration-after-acetaminophen-overdose-in-mice
#20
Bharat Bhushan, Hemantkumar Chavan, Prachi Borude, Yuchao Xie, Kuo Du, Mitchell R McGill, Margitta Lebofsky, Hartmut Jaeschke, Partha Krishnamurthy, Udayan Apte
Epidermal growth factor receptor (EGFR) plays a crucial role in hepatocyte proliferation. Its role in acetaminophen (APAP)-mediated hepatotoxicity and subsequent liver regeneration is completely unknown. Role of EGFR after APAP-overdose in mice was studied using pharmacological inhibition strategy. Rapid, sustained and dose-dependent activation of EGFR was noted after APAP-treatment in mice, which was triggered by glutathione depletion. EGFR-activation was also observed in primary human hepatocytes after APAP-treatment, preceding elevation of toxicity markers...
February 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
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