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drug induced liver toxicity

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https://www.readbyqxmd.com/read/29146462/individual-serum-bile-acid-profiling-in-rats-aids-in-human-risk-assessment-of-drug-induced-liver-injury-due-to-bsep-inhibition
#1
Steven Cepa, David Potter, Lisa Wong, Leah Schutt, Jacqueline Tarrant, Jodie Pang, Xiaolin Zhang, Roxanne Andaya, Laurent Salphati, Yingqing Ran, Le An, Ryan Morgan, Jonathan Maher
Drug-induced liver injury (DILI) has been the most frequent cause of post-marketing drug withdrawals in the last 50years. The multifactorial nature of events that precede severe liver injury in human patients is difficult to model in rodents due to a variety of confounding or contributing factors that include disease state, concurrent medications, and translational species differences. In retrospective analyses, a consistent risk factor for DILI has been the inhibition of the Bile Salt Export Pump (BSEP). One compound known for potent BSEP inhibition and severe DILI is troglitazone...
November 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29146214/-treatments-of-steroid-dependent-nephrotic-syndrome-in-children
#2
A Couderc, E Bérard, V Guigonis, I Vrillon, J Hogan, V Audard, V Baudouin, C Dossier, O Boyer
Primary nephrotic syndrome (NS) is the most common glomerular disease in children. It is characterized by massive proteinuria and hypoalbuminemia. It typically has a sudden onset and more than 70% of patients will experience at least one relapse. An immunological origin has long been postulated, although the precise molecular mechanisms underlying the disease remain debated. Steroids are the first-line therapy with cumulative dose and duration of initial treatment varying among countries. Steroid-sparing agents may be indicated in case of steroid-dependency or frequent relapses...
November 13, 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/29138819/beneficial-effect-of-resveratrol-on-%C3%AE-%C3%A2-naphthyl-isothiocyanate%C3%A2-induced-cholestasis-via-regulation-of-the-fxr-pathway
#3
Lili Ding, Binfeng Zhang, Jinmei Li, Li Yang, Zhengtao Wang
Cholestasis is defined as a functional impairment of bile secretion which results in the accumulation of bile acids (BAs) and other toxic molecules in the blood and liver, however, there are very few effective therapies for cholestasis. The farnesoid X receptor (FXR), as a nuclear receptor for BAs, is important in the regulation of BA levels in enterohepatic circulation. It has previously been demonstrated that activation of the FXR pathway may be a useful strategy with which to treat cholestasis. Resveratrol, one of the important ingredients from grape skins and Chinese medicine Polygonum cuspidatum, resulted in FXR‑activated effects in vitro and exhibited a protective effect against α‑naphthylisothiocyanate (ANIT)‑induced cholestasis through FXR regulation in vivo...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29136767/the-exposure-effect-toxicity-correlation-of-docetaxel-and-magnesium-isoglycyrrhizinate-in-non-small-cell-lung-tumor-bearing-mice
#4
Peijin Li, Suning Li, Hongmei Gu, Qianfeng Lu, Wenjiao Jiang, Xue Pei, Yilin Sun, Hongjiang Xu, Guangji Wang, Kun Hao
To take full advantage of combination therapy of Docetaxel (DTX) and Magnesium isoglycyrrhizinate (MGIG), the pharmacokinetic- pharmacodynamic- toxicodynamics (PK-PD-TD) interaction of DTX and MGIG in non-small cell lung tumor-bearing mice was investigated in the present study. A model, an integrated semi-mechanistic PK-PD-TD, was established for elucidating the exposure-effect-toxicity relationship between DTX and MGIG. A tumor growth and a transit compartmental system were applied to imitate the growth and death of tumor cell...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136753/-metabolomics-study-of-tris-2-chloroethyl-phosphate-induced-hepaotoxicity-and-nephrotoxicity-in-sprague-dawley-rats
#5
W Q Yang, F Zhao, L Li, Y J Fang
Objective: To discuss the potential toxic target organ and the toxic effects and mechanisms of tris (2-chloroethyl) phosphate (TCEP) on SD rats. Methods: 40 female SD rats weaning from milk for 21 days, weighted (50±2.3)g were selected as subjects and marked by the weight. They were randomly divided into 4 groups, namely control group, 50 (L), 100 (M) and 250 (H) mg·kg(-1)·d(-1) dose of TCEP group. Each group has 10 rats, and administrated the corresponding dose of drug or vehicle by mouth, quaque die for 60 days...
November 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/29133762/rare-earth-nanoparticle-induced-cytotoxicity-on-spatial-cognition-memory-of-mouse-brain
#6
Cai-Hou Lin, Gui-Fen Liu, Jing Chen, Yan Chen, Ru-Hui Lin, Hong-Xing He, Jian-Ping Chen
BACKGROUND: Luminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure...
November 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29133031/chloroquine-upregulates-trail-trailr2-expression-and-potentiates-doxorubicin-anti-tumor-activity-in-thioacetamide-induced-hepatocellular-carcinoma-model
#7
Sahar A Helmy, Mohamed El-Mesery, Amro El-Karef, Laila A Eissa, Amal M El Gayar
Impaired apoptosis and systemic toxicity of chemotherapeutic drugs make cancer treatment suboptimal. Thus, there is urgency for drug repurposing which facilitates discovery of safe and effective combination therapy. This study aimed to evaluate chloroquine's (CQ) ability to trigger TRAIL/TRAILR2 apoptotic pathway in thioacetamide (TAA)-induced hepatocellular carcinoma (HCC) either alone or in combination with doxorubicin (DOX). Moreover, its ability to attenuate DOX-induced cardiotoxicity was investigated. TAA was injected in male Sprague Dawely rats (200 mg/kg; ip; 2 times/week) for 16 weeks...
November 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29129047/hepaprotective-effect-of-standardized-ecklonia-stolonifera-formulation-on-ccl%C3%A2-induced-liver-injury-in-sprague-dawley-rats
#8
Jae-Hyuk Byun, Jun Kim, Se-Young Choung
The liver is an essential organ for the detoxification of exogenous xenobiotics, drugs and toxic substances. The incidence rate of non-alcoholic liver injury increases due to dietary habit change and drug use increase. Our previous study demonstrated that Ecklonia stolonifera (ES) formulation has hepatoprotective effect against alcohol-induced liver injury in rat and tacrine-induced hepatotoxicity in HepG2 cells. This present study was designated to elucidate hepatoprotective effects of ES formulation against carbon tetrachloride (CCl₄)-induced liver injury in Sprague Dawley rat...
November 13, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29128607/effects-of-a-new-antiprotozoal-drug-n-n-diphenyl-4-methoxy-benzamidine-on-energy-linked-functions-of-rat-liver-mitochondria
#9
Lyvia Lintzmaier Petiz, Amanda do Rocio Andrade Pires, Aurea Echevarria, Cláudio Eduardo Rodrigues-Santos, Maria Eliane Merlin Rocha, Alexandra Acco, Silvia Maria Suter Correia Cadena
Amidines are chemically characterized by the presence of two nitrogen atoms that bind to the same carbon atom in its structure. Several biological activities have been ascribed to these compounds. Pentamidine, an aromatic diamidine, is effective in the treatment against Pneumocystis carinii and leishmaniasis, but it can also have severe side effects. New amidine derivatives have been synthesized, among them N,N'-diphenyl-4-methoxy-benzamidine (methoxyamidine), which is effective against Leishmania amazonensis (LD50 = 20 μM) and Trypanosoma cruzi (LD50 = 59 nM)...
November 9, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29124333/assessment-of-hepatotoxicity-of-first-line-anti-tuberculosis-drugs-on-wistar-rats
#10
Radhika Sharma, Ramneek Kaur, Manishi Mukesh, Vijay L Sharma
Adverse drug reactions are inevitable risk factors associated with use of modern medicines. First-line anti-tuberculosis drugs contribute to diverse pathological complications, and hepatotoxicity is one of them. This study investigated the effects of anti-TB drugs in combination (rifampicin [RIF] + isoniazid [INH] + pyrazinamide [PZA]) on Wistar rats. Rats were grouped as control group (saline), toxicant group that was given (30.85 mg/kg b.wt., INH + 61.7 mg/kg b.wt., RIF + 132.65 mg/kg b.wt. PZA in dosage extrapolated from dose that is used in human)...
November 9, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29123032/pregnane-x-receptor-promotes-ethanol-induced-hepatosteatosis-in-mice
#11
Sora Choi, Prince Neequaye, Samuel W French, Frank J Gonzalez, Maxwell A Gyamfi
The pregnane X receptor (PXR, NR1I2) is a xenobiotic-sensing nuclear receptor that modulates the metabolic response to drugs and toxic agents. Both PXR activation and deficiency promote hepatic triglyceride accumulation, a hallmark feature of alcoholic liver disease (ALD). However, the molecular mechanism of PXR-mediated activation of ethanol (EtOH)-induced steatosis is unclear. Here, using male wild type (WT) and Pxr-null mice we examined PXR-mediated regulation of chronic EtOH-induced hepatic lipid accumulation and hepatotoxicity...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29115483/hepatocellular-toxicity-of-oxalicumone-a-via-oxidative-stress-injury-and-mitochondrial-dysfunction-in-healthy-human-liver-cells
#12
Si Shi, Limei Yao, Kunbin Guo, Xiangyu Wang, Qi Wang, Weirong Li
The marine‑derived oxalicumone A (POA) has been demonstrated as a potent anti‑tumor bioactive agent for a variety of human carcinoma, but to the best of our knowledge, remains to be evaluated in healthy liver cells. As many drugs distribute preferentially in the liver, the present study aimed to investigate the effects of POA on apoptosis, oxidative stress and mitochondrial function in L‑02 healthy liver cells. A Cell‑Counting kit‑8 assay demonstrated that POA inhibits the proliferation of L‑02 cells in a dose‑ and time‑dependent manner...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29103827/hybrid-drug-combination-anti-diabetic-treatment-of-type-2-diabetic-wistar-rats-with-combination-of-ellagic-acid-and-pioglitazone
#13
Rakesh P Nankar, Mukesh Doble
BACKGROUND: Pioglitazone is an effective drug for the treatment of type 2 diabetes. The drug was suspended from Indian market in June 2013 due to the risk of bladder cancer but was reintroduced in July 2013 because its benefits outweighed the risks. The risks associated with pioglitazone can be minimized if its dose is reduced. HYPOTHESIS: Ellagic acid, a polyphenolic antioxidant, is reported to reduce blood sugar in diabetic rats. The mechanism of anti-diabetic action of ellagic acid is not known...
October 24, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29096561/in-silico-modeling-to-optimize-interpretation-of-liver-safety-biomarkers-in-clinical-trials
#14
Rachel J Church, Paul B Watkins
Current strategies to delineate the risk of serious drug-induced liver injury associated with drugs rely on assessment of serum biomarkers that have been utilized for many decades. In particular, serum alanine aminotransferase and total bilirubin levels are typically used to assess hepatic integrity and function, respectively. Parallel measurement of these biomarkers is utilized to identify patients with drug-induced hepatocellular jaundice ("Hy's Law" cases) which carries at least a 10% risk of death or liver transplant...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29095348/di-2-ethylhexyl-phthalate-and-its-role-in-developing-cholestasis-an-in-vitro-study-on-different-liver-cell-types
#15
Haristi Gaitantzi, Priska Hakenberg, Jannick Theobald, Hagen Heinlein, Chen Cai, Steffan Loff, Stefan Wölfl, Matthias P Ebert, Katja Breitkopf-Heinlein, Ulrike Subotic
OBJECTIVES: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in many polyvinylchloride medical devices and is washed out easily. Thereby critically ill infants can become exposed to DEHP concentrations significantly exceeding the recommended threshold. We suspect DEHP to play an important role in the development of intestinal failure associated liver disease. The aim of this study was therefore, to determine the direct influence of DEHP on different liver cell types. METHODS: HepG2, human upcyte hepatocytes, primary murine hepatocytes, LX-2, human upcyte hepatic stellate cells and liver organoids were cultured with DEHP (0...
October 31, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/29091871/hepatoprotective-effect-of-berberine-against-methotrexate-induced-liver-toxicity-in-rats
#16
Saeed Mehrzadi, Iman Fatemi, Mahdi Esmaeilizadeh, Habib Ghaznavi, Hadi Kalantar, Mehdi Goudarzi
Hepatotoxicity is one of the major side effects of methotrexate (MTX), which restricts the clinical use of this drug. Berberine (BBR) is a natural compound with multiple pharmacological activities such as antioxidant, antiapoptotic and anti-inflammatory effects. In this study, the effect of BBR on MTX-induced hepatotoxicity was studied. A total number of 28 male Wistar rats were randomly divided into four experimental groups. Rats were pretreated with BBR orally with dose of 100mg/kg for 10 consecutive days and MTX (20mg/kg, intraperitoneally) was administrated on the 9th day...
October 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29090021/liver-injury-and-glatiramer-acetate-an-uncommon-association-case-report-and-literature-review
#17
REVIEW
Javier Almeida, Nuria Solà-Valls, Elisa Pose, Yolanda Blanco, María Sepúlveda, Sara Llufriu, Pere Gines, Albert Saiz
We report the case of a 65-year-old woman who presented with a 1-month history of progressive paraparesia associated with a thoracic lesion with irregular ring-like gadolinium enhancement. Biopsy of the lesion confirmed the demyelinating origin and brain magnetic resonance imaging showed additional lesions demonstrative of dissemination in space. Immunomodulatory therapy with glatiramer acetate (GA) was started after having a second relapse 2 months later. Shortly after initiation, the patient developed acute hepatitis...
November 2017: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29082813/identification-and-analysis-of-the-reactive-metabolites-related-to-the-hepatotoxicity-of-safrole
#18
Ai-Hong Yang, Lei Zhang, De-Xian Zhi, Wen-Li Liu, Xue Gao, Xin He
1. Safrole is the main component of volatile oil in Xixin, which has a strong antifungal effect. However, safrole has been shown to be associated with the development of hepatocellular carcinoma. Methylenedioxyphenyl and allyl-benzene substructures of safrole may cause a mechanism-based inhibition (MBI) of CYP450 enzymes (CYPs) and produce reactive metabolites (RMs), resulting in inhibition of enzyme activity and toxic effects. 2. Based on the experiments of CYPs cocktail screening, GSH capture and the IC50 data, we found that safrole had an inhibitory effect on CYP1A2...
October 30, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29082485/tools-to-measure-cell-health-and-cytotoxicity-using-high-content-imaging-and-analysis
#19
Bhaskar S Mandavilli, Robert J Aggeler, Kevin M Chambers
High content screening (HCS)-based multiparametric measurements are very useful in early toxicity testing and safety assessment during drug development, and useful in evaluating the impact from new food supplements and environmental toxicants. Mitochondrial membrane potential, plasma membrane permeability, oxidative stress, phosphoplipidosis, and steatosis are a few of the important markers routinely studied for the assessment of drug-induced liver injury and toxicity. Mitochondrial dysfunction leads to oxidative stress and cell death...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29080465/antihyperglycemic-effect-of-hesperetin-a-citrus-flavonoid-extenuates-hyperglycemia-and-exploring-the-potential-role-in-antioxidant-and-antihyperlipidemic-in-streptozotocin-induced-diabetic-rats
#20
Revathy Jayaraman, Srinivasan Subramani, Shahul Hameed Sheik Abdullah, Muruganathan Udaiyar
Diabetes is the major health problem in modern civilization which occurs due to inadequate metabolism of carbohydrate and lipid could cause tremendous changes in the metabolic activities of liver. In this study, we investigated the antihyperglycemic, antioxidant and antihyperlipidemic effects of hesperetin, a citrus flavonoid against streptozotocin (STZ)-induced experimental rats. To stimulate diabetes mellitus, rats were injected with STZ intraperitoneally at a single dose of 45mg/kg. STZ induced rats showed marked increase in the level of plasma glucose and significant reduction in the level of plasma insulin...
October 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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