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Hepatotoxicity

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https://www.readbyqxmd.com/read/29352486/adverse-effects-of-amphotericin-b-in-children-a-retrospective-comparison-of-conventional-and-liposomal-formulations
#1
Eden C Andrew, Nigel Curtis, Ben Coghlan, Noel Cranswick, Amanda Gwee
AIM: Lipid formulations of amphotericin B, rather than conventional amphotericin (c-amB), are increasingly used despite limited data comparing these preparations in children. Data on the incidence of adverse effects with amphotericin-B at standard doses are scarce. This study aimed to compare the adverse effects associated with standard doses of c-amB and liposomal amphotericin (l-amB) in children. METHODS: Children admitted to the Royal Childrenaposs Hospital Melbourne and treated with c-amB or l-amB between January 2010 and September 2013 were included...
January 19, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29352068/maternal-fetal-disposition-and-metabolism-of-retrorsine-in-pregnant-rats
#2
Xia Li, Xiaojing Yang, E Xiang, Jinyuan Luo, Shuaikai Qiu, Yan Fang, Li Zhang, Yu Guo, Jiang Zheng, Hui Wang
Pyrrolizidine alkaloids (PAs) are extensively synthesized by plants and are commonly present in herbs and foodstuffs, which exhibit hepatotoxicity requiring metabolic activation by cytochrome P450 (CYP) 3A to form the electrophilic metabolites-pyrrolic ester. PAs also cause embryo toxicity, but the metabolic profiles of PAs in fetus and placenta have been far from clear. In this study, we determined the basal metabolic activation of retrorsine (RTS) in rat maternal liver, placenta and fetal liver in vitro, and examined the fetal toxicity and bioactivation of RTS in vivo...
January 19, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29351251/compatibility-with-panax-notoginseng-and-rehmannia-glutinosa-alleviates-the-hepatotoxicity-and-nephrotoxicity-of-tripterygium-wilfordii-via-modulating-the-pharmacokinetics-of-triptolide
#3
Qichun Zhang, Yiqun Li, Mengzhu Liu, Jinao Duan, Xueping Zhou, Huaxu Zhu
Tripterygium wilfordii (TW) and the representative active component triptolide show positive therapeutic effect on the autoimmune disorders and simultaneously ineluctable hepatotoxicity and nephrotoxicity. Combinational application of Panax notoginseng (PN) and Rehmannia glutinosa (RG) weakens the toxicity of TW according the clinical application of traditional Chinese medicine. This article was aimed at the mechanism of decreasing toxicity of TW by the combinational application of PN and RG. Biochemical and pathohistological analysis were utilized to assess the toxicity on liver and kidney in rats administrated with TW, TW-PN, TW-RG and TW-PN-RG for 3 and 7 days...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29348818/high-cyp2e1-activity-correlates-with-hepatofibrogenesis-induced-by-nitrosamines
#4
Jie Gao, Gao-Ju Wang, Zhao Wang, Na Gao, Jing Li, Yun-Fei Zhang, Jun Zhou, Hong-Xin Zhang, Qiang Wen, Han Jin, Hai-Ling Qiao
Hepatofibrosis, which leads to cirrhosis and eventual hepatocellular carcinoma, is a common response to chronic toxin-mediated liver injury. Nitrosamines are potent hepatotoxic agents that cause necrosis and subsequent fibrosis in the liver as a result of cytochrome P450 2E1 (CYP2E1)-dependent metabolism, which generates toxic metabolites that form adducts with nucleic acids, leading to hepatotoxicity and mutagenesis. Herein, CYP2E1 activity and content were determined in fibrotic liver tissue from patients with hepatocellular carcinoma...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348606/amp-activated-protein-kinase-agonist-n6-3-hydroxyphenyl-adenosine-protects-against-fulminant-hepatitis-by-suppressing-inflammation-and-apoptosis
#5
Jin Li, Bo Chen, Liping Zhong, Feng Gao, Haibo Zhu, Fengzhong Wang
Both AMP-activated protein kinase (AMPK) agonist and inhibitor have been reported to protect against fulminant hepatitis, implying that AMPK may play a complicated role in the development of fulminant hepatitis. In this study, we exploited whether the novel AMPK agonist N6-(3-hydroxyphenyl)adenosine (named as M1) exerted protective effects on fulminant hepatitis and whether its beneficial effects were AMPK-dependent. Results showed that intraperitoneal injection of M1 improved liver function, ameliorated liver injury and finally raised the survival rate in D-galactosamine/lipopolysaccharide (GalN/LPS)-treated mice...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29342955/pharmacokinetics-of-schizandrin-and-its-pharmaceutical-products-assessed-using-a-validated-lc-ms-ms-method
#6
Chi-Lin Li, Yung-Yi Cheng, Chen-Hsi Hsieh, Tung-Hu Tsai
Schisandra chinensis has been used as an important component in various prescriptions in traditional Chinese medicine and, more recently, in Western-based medicine for its anti-hepatotoxic effect. The aim of this study was to develop a selective, rapid, and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method for pharmacokinetic studies of schizandrin in rats. Liquid-liquid extraction was used for plasma sample preparation. A UHPLC reverse-phase C18e column (100 mm × 2.1 mm, 2 μm) coupled with a mobile phase of methanol-0...
January 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29342849/comparative-response-of-the-hepatic-transcriptomes-of-domesticated-and-wild-turkey-to-aflatoxin-b%C3%A2
#7
Kent M Reed, Kristelle M Mendoza, Juan E Abrahante, Roger A Coulombe
The food-borne mycotoxin aflatoxin B₁ (AFB₁) poses a significant risk to poultry, which are highly susceptible to its hepatotoxic effects. Domesticated turkeys (Meleagris gallopavo) are especially sensitive, whereas wild turkeys (M. g. silvestris) are more resistant. AFB₁ toxicity entails bioactivation by hepatic cytochrome P450s to the electrophilic exo-AFB₁-8,9-epoxide (AFBO). Domesticated turkeys lack functional hepatic GST-mediated detoxification of AFBO, and this is largely responsible for the differences in resistance between turkey types...
January 13, 2018: Toxins
https://www.readbyqxmd.com/read/29342206/silymarin-prevents-acetaminophen-induced-hepatotoxicity-in-mice
#8
Zuzana Papackova, Marie Heczkova, Helena Dankova, Eva Sticova, Alena Lodererova, Lenka Bartonova, Martin Poruba, Monika Cahova
Acetaminophen or paracetamol (APAP) overdose is a common cause of liver injury. Silymarin (SLM) is a hepatoprotective agent widely used for treating liver injury of different origin. In order to evaluate the possible beneficial effects of SLM, Balb/c mice were pretreated with SLM (100 mg/kg b.wt. per os) once daily for three days. Two hours after the last SLM dose, the mice were administered APAP (300 mg/kg b.wt. i.p.) and killed 6 (T6), 12 (T12) and 24 (T24) hours later. SLM-treated mice exhibited a significant reduction in APAP-induced liver injury, assessed according to AST and ALT release and histological examination...
2018: PloS One
https://www.readbyqxmd.com/read/29341879/mechanisms-of-mitochondrial-toxicity-of-the-kinase-inhibitors-ponatinib-regorafenib-and-sorafenib-in-human-hepatic-hepg2-cells
#9
Franziska Paech, Cécile Mingard, David Grünig, Vanessa F Abegg, Jamal Bouitbir, Stephan Krähenbühl
Previous studies have shown that certain kinase inhibitors are mitochondrial toxicants. In the current investigation, we determined the mechanisms of mitochondrial impairment by the kinase inhibitors ponatinib, regorafenib, and sorafenib in more detail. In HepG2 cells cultured in galactose and exposed for 24 hours, all three kinase inhibitors investigated depleted the cellular ATP pools at lower concentrations than cytotoxicity occurred, compatible with mitochondrial toxicity. The kinase inhibitors impaired the activity of different complexes of the respiratory chain in HepG2 cells exposed to the toxicants for 24 hours and in isolated mouse liver mitochondria exposed acutely...
January 13, 2018: Toxicology
https://www.readbyqxmd.com/read/29340156/hepatotoxicity-in-hyperthyroid-patient-after-consecutive-methimazole-and-propylthiouracil-therapies
#10
Fernando Gomez-Peralta, Pablo Velasco-Martínez, Cristina Abreu, María Cepeda, Marta Fernández-Puente
Methimazole (MMI) and propylthiouracil (PTU) are widely used antithyroid drugs (ATD) that have been approved for the treatment of hyperthyroidism. Hepatotoxicity may be induced by these drugs, though they exert dissimilar incidence rates of hepatotoxicity and, possibly, with different underlying pathogenic mechanisms. We report the case of a 55-year-old woman with no relevant medical history diagnosed with hyperthyroidism due to Graves' disease, who developed two episodes of acute hepatitis concurrent with the consecutive administration of two different ATDs, first MMI and then PTU...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29339102/spirulina-ameliorates-methotrexate-hepatotoxicity-via-antioxidant-immune-stimulation-and-proinflammatory-cytokines-and-apoptotic-proteins-modulation
#11
Asmaa F Khafaga, Yasser S El-Sayed
AIMS: Methotrexate (MTX) is an efficient cytotoxic drug used against various carcinogenic, inflammatory and autoimmune diseases; however, the hepatotoxicity of MTX limits its use. Therefore, the present study aimed to evaluate the potential hepatoprotective and immune-stimulant effect of Spirulina platensis (SP) against MTX acute toxicity. MAIN METHODS: Thirty-two male Wistar rats were randomly allocated into the following four groups (n = 8): control, MTX (20 mg/kg bwt, single ip injection), SP (500 mg/kg bwt, oral gavage daily for 21 days), and MTX+SP...
January 12, 2018: Life Sciences
https://www.readbyqxmd.com/read/29338970/baicalein-and-baicalin-alleviate-acetaminophen-induced-liver-injury-by-activating-nrf2-antioxidative-pathway-the-involvement-of-erk1-2-and-pkc
#12
Liang Shi, Zhanxia Hao, Shaobo Zhang, Mengjuan Wei, Bin Lu, Zhengtao Wang, Lili Ji
Acetaminophen (APAP)-induced hepatotoxicity is the main cause of drug-induced liver injury. This study investigated the protection of baicalin and its aglycone baicalein against APAP-induced hepatotoxicity and its mechanism. Baicalein and baicalin alleviated APAP-induced hepatotoxicity both in vitro and in vivo. Moreover, baicalin-provided this protection was not diminished in hepatocytes or mice treated with β-glucuronidase inhibitor. Results of liver glutathione (GSH) and reactive oxygen species (ROS) formation demonstrated the alleviation of baicalein and baicalin on APAP-induced liver oxidative stress injury...
January 12, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29337684/hepatotoxicity-associated-with-statins
#13
Bensu Karahalil, Emine Hare, Göksel Koç, İrem Uslu, Kerem Şentürk, Yağmur Özkan
Treatment with statins is known all over the world. They are generally considered safe at therapeutic doses. Nevertheless, clinical trials are not enough to assess their scarce adverse effects such as idiosyncratic drug induced liver injury (DILI). Due to some conditions, such as concomitant usage (drug-drug interaction using an identical metabolising enzyme) and genetic polymorphisms, there is an increasing concern about their safety. Hepatotoxicity and rhabdomyolysis have begun to appear in published studies...
December 20, 2017: Arhiv za Higijenu Rada i Toksikologiju
https://www.readbyqxmd.com/read/29337682/adverse-effects-of-organophosphorus-pesticides-on-the-liver-a-brief-summary-of-four-decades-of-research
#14
Somayyeh Karami-Mohajeri, Ahmad Ahmadipour, Hamid-Reza Rahimi, Mohammad Abdollahi
Organophosphorus pesticides (OPs) are widely used volatile pesticides that have harmful effects on the liver in acute and chronic exposures. This review article summarises and discusses a wide collection of studies published over the last 40 years reporting on the effects of OPs on the liver, in an attempt to propose general mechanisms of OP hepatotoxicity and possible treatment. Several key biological processes have been reported as involved in OP-induced hepatotoxicity such as disturbances in the antioxidant defence system, oxidative stress, apoptosis, and mitochondrial and microsomal metabolism...
December 20, 2017: Arhiv za Higijenu Rada i Toksikologiju
https://www.readbyqxmd.com/read/29333041/pharmacological-evaluation-of-hepatoprotective-activity-of-ahpl-aytab-0613-tablet-in-carbon-tetrachloride-ethanol-and-paracetamol-induced-hepatotoxicity-models-in-wistar-albino-rats
#15
Sanjay U Nipanikar, Sohan S Chitlange, Dheeraj Nagore
Background: Hepatotoxicity ultimately leads to liver failure. Conventional treatment options for hepatotoxicity are limited and not safe. Objective: Formulation AHPL/AYTAB/0613 is developed to provide safer and effective hepatoprotective drug of natural origin. A study was conducted to evaluate hepatoprotective activity of AHPL/AYTAB/0613 (three dosages) in comparison with marketed formulations in carbon tetrachloride (CCl4), ethanol, and paracetamol-induced hepatotoxicity in Wistar albino rats...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29332586/recent-developments-on-multi-target-directed-tacrines-for-alzheimer-s-disease-i-the-pyranotacrines
#16
Alejandro Romero, Jose Marco-Contelles
Tacrine was the first drug to displayed beneficial effects on cognitive impairment of Alzheimer disease (AD) patients. Unfortunately, many treated patients displayed related hepatotoxicity, and hence this drug was withdrawn. Notwithstanding, recent efforts have been directed to design small tacrine analogues targeting the underlying pathogenic mechanisms of AD. In this context, we have developed a number of pyranotacrines by changing the benzene fused ring in tacrine by a 4H-pyran. Based on this strategy, in this account we will show the tacrine analogues that we have designed, synthesized and evaluated as potential multipotent agents for AD in the last years...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29332585/new-tacrines-as-anti-alzheimer-s-disease-agents-ii-the-benzo-chromenopyranotacrines
#17
Maria J Oset-Gasque, Jose Marco-Contelles
Tacrine was the first drug approved by FDA (US) for the treatment of Alzheimer's disease suffering patients. Nowadays, this agent has been withdrawn from the clinics due to secondary effects, among them, and the most important, its hepatotoxicity. However, the research on new tacrine analogues devoid of these therapeutically undesirable effects, but benefiting of their high and well known positive cholinergic power, has produced a number of new non-hepatotoxic tacrines. In this context, in our laboratory, in the last years we have prepared a new heterocyclic tacrines by changing the benzene ring present in tacrine by appropriate heterocyclic motifs...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29332319/treatment-of-latent-tuberculosis-infection-and-its-clinical-efficacy
#18
REVIEW
Hyung Woo Kim, Ju Sang Kim
The role of the treatment for latent tuberculosis infection (LTBI) has been underscored in the intermediate tuberculosis (TB) burden countries like South Korea. LTBI treatment is recommended only for patients at risk for progression to active TB-those with frequent exposure to active TB cases, and those with clinical risk factors (e.g., immunocompromised patients). Recently revised National Institute for Health and Care Excellence (NICE) guideline recommended that close contacts of individuals with active pulmonary or laryngeal TB, aged between 18 and 65 years, should undergo LTBI treatment...
January 2018: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29331654/in-vitro-and-in-vivo-metabolic-activation-of-rhein-and-characterization-of-glutathione-conjugates-derived-from-rhein
#19
Yang Xu, Xu Mao, Boyang Qin, Ying Peng, Jiang Zheng
Rhein (RH), 4,5-dihydroxyanthrauinone-2-carboxylic acid, is found in rhubarb (Dahuang), a traditional herbal medicine. RH has reportedly demonstrated multiple pharmacologic properties. Previous studies have also shown that RH induced hepatotoxicity, but the mechanisms of the adverse effect remain unknown. The major objective of the present study was to study the metabolic pathways of RH in order to identify potential reactive metabolites. One mono-hydroxylation metabolite (M1) was detected in urine and bile of rats given RH...
January 10, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29331651/activation-of-p62-keap1-nrf2-antioxidant-pathway-in-the-early-stage-of-acetaminophen-induced-acute-liver-injury-in-mice
#20
Zhenyu Shen, Yu Wang, Zhenhui Su, Ruirui Kou, Keqin Xie, Fuyong Song
Acetaminophen (APAP) overdose can cause severe liver failure even death. Nearly half of drug-induced liver injury is attributed to APAP in the US and many European countries. Oxidative stress has been validated as a critical event involved in APAP-induced liver failure. p62/SQSTM1, a selective autophagy adaptor protein, is reported to regulate Nrf2-ARE antioxidant pathway in response to oxidative stress. However, the exact role of p62-keap1-Nrf2 antioxidant pathway in APAP-induced hepatotoxicity remains unknown...
January 10, 2018: Chemico-biological Interactions
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