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Hepatotoxicity

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https://www.readbyqxmd.com/read/28817570/increased-hepatotoxicity-among-hiv-infected-adults-co-infected-with-schistosoma-mansoni-in-tanzania-a-cross-sectional-study
#1
Amon I Marti, Soledad Colombe, Peter J Masikini, Samuel E Kalluvya, Luke R Smart, Bahati M Wajanga, Hyasinta Jaka, Robert N Peck, Jennifer A Downs
INTRODUCTION: Little is known about hepatotoxicity in patients with schistosome and HIV co-infections. Several studies have reported increased liver enzymes and bilirubin levels associated with schistosome infection. We investigated whether HIV-infected adults on antiretroviral therapy who had S. mansoni co-infection had a higher prevalence of hepatotoxicity than those without. METHODOLOGY/PRINCIPAL FINDINGS: We determined the presence and grade of hepatotoxicity among 305 HIV-infected outpatients who had been on medium-term (3-6 months) and long-term (>36 months) antiretroviral therapy in a region of northwest Tanzania where S...
August 17, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28816585/antioxidative-and-anti-inflammatory-activities-of-akebia-quinata-extracts-in-an-in-vitro-model-of-acute-alcohol-induced-hepatotoxicity
#2
Sang Hoon Lee, Young Sun Song, Yoon Hwa Jeong, Kwang Suk Ko
This study investigated the effects of Akebia quinata (AQ) leaf and fruit extract on acute alcohol-induced hepatotoxicity in AML12 cells. Different concentrations of AQ extracts (250 and 2500 μg/mL) were used to treat the AML12 cells with or without ethanol for 24 h for inducing acute alcohol cytotoxicity. AQ extract-treated AML12 cells showed enhanced expression of GSH-synthesizing enzymes and suppressed expression of oxidative stress makers such as NOX4, and decreased expression of tumor necrosis factor-α, inflammatory marker, in acute alcohol-induced hepatotoxicity...
August 17, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28812394/the-use-of-sustained-low-efficiency-dialysis-sled-in-massive-paracetamol-overdose
#3
Anselm Wong, Roger L K Tong, Liam Ryan, Tim Crozier, Andis Graudins
CONTEXT: Massive paracetamol ingestion causing mitochondrial dysfunction is uncommon. Use of sustained low-efficiency dialysis (SLED) to improve acidaemia and enhance paracetamol elimination has not been previously described. CASE DETAILS: A 44-year-old male presented to the emergency department 2.5 hours post overdose of 200 g (2.5 g/kg) of paracetamol. Examination revealed a BP 85/60 mmHg, pulse 112 bpm, temperature 33.9 °C and blood glucose of 13...
August 16, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28812385/increased-acetaminophen-related-calls-to-finnish-pic-better-reflect-acetaminophen-sales-than-serious-poisonings
#4
Mikko J Parry, Helena Isoniemi, Anna-Maria Koivusalo, Kalle Hoppu
OBJECTIVE: Acetaminophen (APAP) or paracetamol is a commonly encountered medicine in poisonings. We studied the changes in APAP related calls to the Finnish poison information centre (FPIC), and serious intoxications, involving hepatotoxicity or death in 2001-2014. These data were compared with paracetamol sales in Finland. METHODS: This is a retrospective analysis of the FPIC database calls, national cause of death registry, registries of liver transplantations and molecular adsorbent recycling system (MARS)-treated patients from Helsinki University Hospital together with the National Institute of Health and Welfare registry of patients hospitalized...
August 16, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28812380/analysis-of-an-8-hour-acetylcysteine-infusion-protocol-for-repeated-supratherapeutic-ingestion-rsti-of-paracetamol
#5
Anselm Wong, Naren Gunja, Richard McNulty, Andis Graudins
OBJECTIVES: In Australia, the treatment guideline for patients with repeated supratherapeutic ingestion (RSTI) of paracetamol recommends an abbreviated acetylcysteine regimen if the paracetamol concentration is low (<10 mg/L) and alanine aminotransferase (ALT) is normal or static after 8 hours of infusion. There are currently no studies of this recommendation. METHOD: A retrospective review of paracetamol overdose presentations from October 2009 to August 2016 in two hospital toxicology networks was performed...
August 16, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28810188/novel-tacrine-derivatives-exhibiting-improved-acetylcholinesterase-inhibition-design-synthesis-and-biological-evaluation
#6
Eeda Koti Reddy, Chandran Remya, Kumar Mantosh, Ayyiliath M Sajith, R V Omkumar, C Sadasivan, Shaik Anwar
A novel series of twenty four tacrine derivatives were designed and synthesised. Among these, thirteen were taken for the acetylcholinesterase (AChE) inhibition studies. Three compounds such as 4c, 6c and 6f were found to possess significant AChE inhibitory properties with IC50 values 12.97 ± 0.47 nM, 5.17 ± 0.24 nM and 7.14 ± 0.78 nM respectively. In silico docking studies revealed that these compounds can bind strongly in the active site of the enzyme and prevent enzyme-substrate interactions...
August 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28809737/acute-liver-failure-due-to-etodolac-a-selective-cycloxygenase-2-cox-2-inhibitor-non-steroidal-anti-inflammatory-drug-established-by-rucam-based-causality-assessment
#7
Sunil Taneja, Pramod Kumar, Sahaj Rathi, Ajay Duseja, Virendra Singh, Radha Krishan Dhiman, Yogesh Kumar Chawla
Drug induced liver injury is a common cause of acute liver failure (ALF). While most of these cases are due to dose dependent hepatotoxicity with acetaminophen, idiosyncratic drug-induced liver injury (DILI) is responsible for about 15% cases of ALF. Antibiotics are the most common cause of idiosyncratic DILI as well as DILI induced ALF. Etodolac is a selective cycloxygenase- 2 (COX -2) inhibitor non-steroidal anti-inflammatory drug used as an analgesic and anti-inflammatory in musculoskeletal diseases. Severe liver impairment is extremely rare...
August 8, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28808395/hepatoprotective-effect-of-gallotannin-enriched-extract-isolated-from-gall-on-hydrogen-peroxide-induced-cytotoxicity-in-hepg2-cells
#8
Jun Go, Ji Eun Kim, Eun Kyoung Koh, Sung Hwa Song, Hyun Gu Kang, Young Hee Lee, Han Do Kim, Jin Tae Hong, Dae Youn Hwang
BACKGROUND: Gall (Galla Rhois [GR]) is known to have antibacterial, anti-inflammatory, antimetastatic, and anti-invasion activities and exert hepatoprotective effects. However, the hepatoprotective effects of gallotannin-enriched GR (GEGR) and their mechanisms have not yet been investigated. OBJECTIVE: The potential protective effect of GEGR against hepatotoxicity induced by hydrogen peroxide (H2O2) was investigated. MATERIALS AND METHODS: Changes in cell viability, apoptosis protein expression, and reactive oxygen species (ROS) generation were determined in HepG2 cells that were pretreated with four different concentrations of GEGR (6...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28808207/moringa-oleifera-based-diet-protects-against-nickel-induced-hepatotoxicity-in-rats
#9
Oluyomi Stephen Adeyemi, Cincin Sokolayemji Aroge, Musbau Adewumi Akanji
Multiple health-promoting effects have been attributed to the consumption of Moringa oleifera leaves, as part of diet without adequate scientific credence. This study evaluated the effect of M. oleifera-based diets on nickel (Ni) - induced hepatotoxicity in rats. Male rats assigned into six groups were given oral administration of 20 mg/kg body weight nickel sulfate in normal saline and either fed normal diet orM. oleifera-based diets for 21 days. All animals were sacrificed under anesthesia 24 hours after the last treatment...
July 13, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28807851/toxic-pyrrolizidine-alkaloids-provide-a-warning-sign-to-overuse-of-the-ethnomedicine-arnebia-benthamii
#10
Latif Ahmad, He Yi, Jia-Chen Hao, Andrew Semotiuk, Quan-Ru Liu, Paras Mazari
ETHNOPHARMACOLOGICAL RELEVANCE: From early times man has used medicinal plants for the treatment of various ailments and basic health care needs. The use of herbal medicines has increased day by day and with this, so do reports of adverse events, poisoning, and suspected toxicity. Similarly, the indigenous communities of Neelum Valley in Azad Kashmir commonly use Arnebia benthamii (Wall. ex G.Don) I.M.Johnst. for medicinal purposes to treat various human aliments. Besides their medicinal uses, it also contains hepatotoxic pyrrolizidine alkaloids (PAs)...
August 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28807226/liver-metabolomics-study-reveals-protective-function-of-phyllanthus-urinaria-against-ccl4-induced-liver-injury
#11
Qing Guo, Qian-Qian Zhang, Jia-Qing Chen, Wei Zhang, Hong-Cong Qiu, Zun-Jian Zhang, Bu-Ming Liu, Feng-Guo Xu
Phyllanthus Urinaria L. (PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl4-induced liver injury in rats...
July 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28806057/rational-design-and-multi-biological-profiling-of-novel-donepezil-trolox-hybrids-against-alzheimer-s-disease-with-cholinergic-antioxidant-neuroprotective-and-cognition-enhancing-properties
#12
Pei Cai, Si-Qiang Fang, Xue-Lian Yang, Jia-Jia Wu, Qiao-Hong Liu, Hao Hong, Xiao-Bing Wang, Lingyi Kong
A novel series of donepezil-trolox hybrids were designed, synthesized and evaluated as multifunctional ligands against Alzheimer's disease (AD). Biological assays showed that these derivatives possessed moderate to good inhibitory activities against acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) as well as remarkable antioxidant effects. The optimal compound 6d exhibited balanced functions with good inhibition against hAChE (IC50 = 0.54 μM) and hMAO-B (IC50 = 4.3 μM), significant antioxidant activity (41...
August 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28805726/chemical-identity-of-interaction-of-protein-with-reactive-metabolite-of-diosbulbin-b-in-vitro-and-in-vivo
#13
Kai Wang, Dongju Lin, Xiucai Guo, Wenlin Huang, Ying Peng, Jiang Zheng
Diosbulbin B (DIOB), a hepatotoxic furan-containing compound, is a primary ingredient in Dioscorea bulbifera L., a common herbal medicine. Metabolic activation is required for DIOB-induced liver injury. Protein covalent binding of an electrophilic reactive intermediate of DIOB is considered to be one of the key mechanisms of cytotoxicity. A bromine-based analytical technique was developed to characterize the chemical identity of interaction of protein with reactive intermediate of DIOB. Cysteine (Cys) and lysine (Lys) residues were found to react with the reactive intermediate to form three types of protein modification, including Cys adduction, Schiff's base, and Cys/Lys crosslink...
August 14, 2017: Toxins
https://www.readbyqxmd.com/read/28803882/changes-in-coumarin-kinetics-and-subcellular-localization-of-cyp2e1-contribute-to-bile-duct-damage-and-reduce-hepatocellular-damage-after-repeated-administration-of-coumarin-in-rats
#14
Yasuhiro Tanaka, Wataru Fujii, Hisako Hori, Yoshinori Kitagawa, Kiyokazu Ozaki
Coumarin exhibits different hepatotoxicity in rats depending on the administration frequency. To investigate the underlying mechanisms for the differences, we administered coumarin to rats as a single dose or repeatedly for 4 weeks. We found large increases in blood levels of liver enzymes and noticeable centrilobular hepatic necrosis after a single dose of coumarin. After repeated administration, enzyme levels mildly increased, while those of γ-GTP and total bilirubin significantly increased, suggesting bile duct damage...
August 10, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28803824/the-clinical-spectrum-of-hepatic-manifestations-in-chronic-lymphocytic-leukemia
#15
REVIEW
Natalia Kreiniz, Ofrat Beyar Katz, Aaron Polliack, Tamar Tadmor
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, characterized by the presence of long-lived circulating leukemic cells in the peripheral blood that may infiltrate all organs, particularly those of the reticulo-endothelial system. Liver enlargement and elevation of liver enzymes related to specific involvement by the underlying disease are well-recognized features in these patients. In CLL, the differential diagnosis of liver disorders is broad and includes liver infiltration by leukemic cells, immunologic manifestations associated with CLL, primary and secondary hepatic malignancies, drug-induced hepatotoxicity, infections, and Richter transformation...
July 23, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28803056/analysis-of-microcystin-lr-and-nodularin-using-triple-quad-liquid-chromatography-tandem-mass-spectrometry-and-histopathology-in-experimental-fish
#16
Daljit Vudathala, Stephen Smith, Lester Khoo, David D Kuhn, Mary E Mainous, James Steadman, Lisa Murphy
Microcystins (MCs) are hepatotoxic cyanobacterial metabolites produced sporadically in aquatic environments under favorable environmental conditions. Affinity of these toxins to covalently bind with protein phosphatases poses a challenge in their detection. Lemieux oxidation to release 2-methyl-3-methoxy-4-phenylbutyric acid (MMPB), a common moiety to all MCs congeners, has been used in detection of these compounds, however a lack of sensitivity has limited the usefulness of the method. In this study, modifications of the oxidation and solid phase extraction procedures, combined with a sensitive LC/MS/MS (liquid chromatography/mass spectrometry) detection, have resulted in 25 ng/g method detection limits in both liver and plasma samples...
August 10, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28803044/new-racemic-annulated-pyrazolo-1-2-b-phthalazines-as-tacrine-like-ache-inhibitors-with-potential-use-in-alzheimer-s-disease
#17
Leili Jalili-Baleh, Hamid Nadri, Alireza Moradi, Syed Nasir Abbas Bukhari, Mojtaba Shakibaie, Mandana Jafari, Mostafa Golshani, Farshad Homayouni Moghadam, Loghman Firoozpour, Ali Asadipour, Saeed Emami, Mehdi Khoobi, Alireza Foroumadi
A novel series of tacrine-like compounds 7a-u possessing a fused pyrazolo[1,2-b]phthalazine structure were designed and synthesized as potent and selective inhibitors of AChE. The in-vitro biological assessments demonstrated that several compounds had high anti-AChE activity at nano-molar level. The more promising compound 7l with IC50 of 49 nM was 7-fold more potent than tacrine and unlike tacrine, it was highly selective against AChE over BuChE. The cell-based assays against hepatocytes (HepG2) and neuronal cell line (PC12) revealed that 7l had significantly lower hepatotoxicity compared to tacrine, with additional neuroprotective activity against H2O2-induced damage in PC12 cells...
July 31, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28800917/thyrotoxic-rubber-antioxidants-2-mercaptobenzimidazole-and-its-methyl-derivatives-cause-both-inhibition-and-induction-of-drug-metabolizing-activity-in-rat-liver-microsomes-after-repeated-oral-administration
#18
Atsuko Miyajima, Kazue Sakemi-Hoshikawa, Makoto Usami, Katsuyoshi Mitsunaga, Tomohiko Irie, Yasuo Ohno, Momoko Sunouchi
We examined the effects of thyrotoxic rubber antioxidants, 2-mercaptobenzimidazole (MBI, 0.3 mmol/kg/day) and its methyl derivatives, methyl-MBIs [4-methyl-MBI (4-MeMBI, 0.6 mmol/kg/day), 5-methyl-MBI (5-MeMBI, 0.6 mmol/kg/day), and 4(or 5)-methyl-MBI (4(5)-MeMBI, 0.6 or 1.2 mmol/kg/day)], on the drug-metabolizing activity in male rat liver microsomes by 8-day repeated oral administration. The weight of liver and thyroid were increased by all the test chemicals; MBI was most potent, and there was no additive or synergistic effect between 4-MeMBI and 5-MeMBI...
August 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28800171/antioxidant-protection-by-%C3%AE-selenoamines-against-thioacetamide-induced-oxidative-stress-and-hepatotoxicity-in-mice
#19
Sílvio Terra Stefanello, Diane Duarte Hartmann, Guilherme Pires Amaral, Aline Alves Courtes, Martim T B Leite, Thayanara Cruz da Silva, Débora Farina Gonçalves, Micaela B Souza, Pâmela Carvalho da Rosa, Luciano Dornelles, Félix Alexandre Antunes Soares
Thioacetamide (TAA) is a hepatotoxin that rapidly triggers the necrotic process and oxidative stress in the liver. Nevertheless, organic selenium compounds, such as β-selenoamines, can be used as pharmacological agents to diminish the oxidative damage. Thus, the aim of this study was to investigate the protective effect of the antioxidant β-selenoamines on TAA-induced oxidative stress in mice. Here, we observed that a single intraperitoneal injection of TAA (200 mg/kg) dramatically elevated some parameters of oxidative stress, such as lipid peroxidation and reactive oxygen species (ROS) production, as well as depleted cellular antioxidant defenses...
August 11, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28799976/effect-of-gene-gene-and-gene-environment-interactions-associated-with-antituberculosis-drug-induced-hepatotoxicity
#20
Julián G Chamorro, Jorge P Castagnino, Omar Aidar, Rosa M Musella, Ana Frías, Mabel Visca, Mabel Nogueras, Lucas Costa, Alessandro Perez, Fabio Caradonna, Gabriela F de Larrañaga
OBJECTIVES: This study evaluated the association between environmental factors and genetic variations in enzymes that metabolize antituberculosis (anti-TB) drugs [arylamine N-acetyltransferase 2, cytochrome P450 2E1 (CYP2E1), glutathione S-transferase theta 1 (GSTT1), and glutathione S-transferase mu 1] with antituberculosis drug-induced hepatotoxicity (ATDH). We also investigated the potential gene-gene and gene-environment interactions as well as their association with ATDH development in a population of hospitalized TB patients from Buenos Aires...
August 9, 2017: Pharmacogenetics and Genomics
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